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Background: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer. Methods: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging. Results: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031). Conclusion: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence. [ABSTRACT FROM AUTHOR]

Background: In many low- and middle-income countries, data on the prevalence of surgical diseases have been derived primarily from hospital-based studies, which may lead to an underestimation of disease burden within the community. Community-based prevalence studies may provide better estimates of surgical need to enable proper resource allocation and prioritization of needs. This study aims to assess the prevalence of common surgical conditions among children in a diverse rural and urban population in Nigeria. Methods: Descriptive cross-sectional, community-based study to determine the prevalence of congenital and acquired surgical conditions among children in a diverse rural-urban area of Nigeria was conducted. Households, defined as one or more persons 'who eat from the same pot' or slept under the same roof the night before the interview, were randomized for inclusion in the study. Data was collected using an adapted and modified version of the interviewer-administered questionnaire—Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool and analysed using the REDCap web-based analytic application. Main results: Eight-hundred-and-fifty-six households were surveyed, comprising 1,883 children. Eighty-one conditions were identified, the most common being umbilical hernias (20), inguinal hernias (13), and wound injuries to the extremities (9). The prevalence per 10,000 children was 85 for umbilical hernias (95% CI: 47, 123), and 61 for inguinal hernias (95% CI: 34, 88). The prevalence of hydroceles and undescended testes was comparable at 22 and 26 per 10,000 children, respectively. Children with surgical conditions had similar sociodemographic characteristics to healthy children in the study population. Conclusion: The most common congenital surgical conditions in our setting were umbilical hernias, while injuries were the most common acquired conditions. From our study, it is estimated that there will be about 2.9 million children with surgically correctable conditions in the nation. This suggests an acute need for training more paediatric surgeons. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the diagnostic accuracy of breast MRI for detecting residual tumor and the tumor size whether it would be affected after neoadjuvant chemotherapy. Methods: Total 109 patients with NAC and 682 patients without NAC were included in this retrospective study. Measurement of the largest diameter of tumors at pathology was chosen as gold standard and compared with preoperative breast MRI. A concordance threshold of ±25% of maximal tumor size was used. The accuracy of MRI was graded as concordant, underestimation, or overestimation rate. Further subgroup analysis with tumor stages, histologic subgroups and intrinsic subtypes was performed. Results: The post-NAC MRI was associated with 92.5% sensitivity, 55.2% specificity, 85.1% positive predictive value, 72.7% negative predictive value, and overall 82.6% accuracy for detecting residual tumor. In determining tumor size, the overall concordance rates of the non-NAC group and the NAC group were 43.5% and 41.3%, respectively (p = 0.678). But the overestimation rate and underestimation rate were 26.6% and 32.1% for NAC group, and 52.9% and 3.5% for the non-NAC group (p<0.001). While in the subgroups analysis, the concordance rate of the NAC group (26.7%) was lower than that of the non-NAC group (82.1%) at T3 stage (p<0.001). There were no statistically significant differences between different tumor histologic subgroups and intrinsic subtypes. Conclusions: The overall accuracy of MRI in predicting tumor size was not affected by NAC; however, it tends to underestimate tumor size after NAC, especially in patients with T3 lesions and above. [ABSTRACT FROM AUTHOR]

Although there is good evidence to indicate a major role of intrinsic impairment of the contractile apparatus in muscle weakness seen in several pathophysiological conditions, the factors responsible for control of myofibrillar function are not fully understood. To investigate the role of mechanical load in myofibrillar function, we compared the skinned fiber force between denervated (DEN) and dexamethasone-treated (DEX) rat skeletal muscles with or without neuromuscular electrical stimulation (ES) training. DEN and DEX were induced by cutting the sciatic nerve and daily injection of dexamethasone (5 mg/kg/day) for 7 days, respectively. For ES training, plantarflexor muscles were electrically stimulated to produce four sets of five isometric contractions each day. In situ maximum torque was markedly depressed in the DEN muscles compared to the DEX muscles (-74% vs. -10%), whereas there was not much difference in the degree of atrophy in gastrocnemius muscles between DEN and DEX groups (-24% vs. -17%). Similar results were obtained in the skinned fiber preparation, with a greater reduction in maximum Ca2+-activated force in the DEN than in the DEX group (-53% vs. -16%). Moreover, there was a parallel decline in myosin heavy chain (MyHC) and actin content per muscle volume in DEN muscles, but not in DEX muscles, which was associated with upregulation of NADPH oxidase (NOX) 2, neuronal nitric oxide synthase (nNOS), and endothelial NOS expression, translocation of nNOS from the membrane to the cytosol, and augmentation of mRNA levels of muscle RING finger protein 1 (MuRF-1) and atrogin-1. Importantly, mechanical load evoked by ES protects against DEN- and DEX-induced myofibrillar dysfunction and these molecular alterations. Our findings provide novel insights regarding the difference in intrinsic contractile properties between DEN and DEX and suggest an important role of mechanical load in preserving myofibrillar function in skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: The partograph has been endorsed by World Health Organization (WHO) since 1994 which presents an algorithm for assessing maternal and foetal conditions and labor progression. Monitoring labour with a partograph can reduce adverse pregnancy outcomes such as prolonged labor, emergency C-sections, birth asphyxia and stillbirths. However, partograph use is still very low, particularly in low and middle income countries (LMICs). In Bangladesh the reported partograph user rate varies from 1.4% to 33.0%. Recently, an electronic version of the partograph, with the provision of online data entry and user aid for emergency clinical support, has been tested successfully in different settings. With this proven evidence, we conducted and operations research to test the feasibility and effectiveness of implementing an e-partograph, for the first time, in 2 public hospitals in Bangladesh Methods: We followed a prospective crossover design. Two secondary level referral hospitals, Jessore and Kushtia District Hospital (DH) were the study sites. All pregnant women who delivered in the study hospitals were the study participants. All nurse-midwives working in the labor ward of study hospitals were trained on appropriate use of both types of partograph along with standard labour management guidelines. Collected quantitative data was analyzed using SPSS 23 statistical software. Discrete variables were expressed as percentages and presented as frequency distribution and cross tabulations. Chi square tests were employed to test the association between exposure and outcome variables. Potential confounding factors were adjusted using multivariate binary logistic regression methods. Ethical approval was obtained from the institutional review board of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). Findings: In total 2918 deliveries were conducted at Jessore DH and 2312 at Kushtia DH during one-year study period. Of them, 1012 (506 in each facility) deliveries were monitored using partograph (paper or electronic). The trends of facility based C-section rates was downwards in both the hospitals; 43% to 37% in Jessore and from 36% to 25% in Kushtia Hospital. There was a significant reduction of prolonged labour with e-partograph use. In Kushtia DH, the prolonged labour rate was 42% during phase 1 with the paper version which came down to 29% during phase-2 with the e-partograph use. The similar result was observed in Jessore DH where the prolonged labour rate reduced to 7% with paper partograph from the reported 30% prolonged labour with e-partograph. The e-partograph user rate was higher than the paper partograph during both phases (phase 1: 3.31, CI: 2.04–5.38, p < .001 and in phase 2: 15.20 CI: 6.36–36.33, p < .001) after adjusting for maternal age, parity, gestational age, religion, mother’s education, husband’s education, and fetal sex Conclusion: The partograph user rate has significantly improved with the e- partograph and was associated with an overall reduction in cesarean births. Use of the e-partograph was also associated with reduced rates of prolonged labour. This study has added to the growing body of evidence on the positive impact of e-partograph use. We recommend implementing e-partograph intervention at scale in both public and private hospitals in Bangladesh. Trial registration: ClinicalTrials.gov . [ABSTRACT FROM AUTHOR]

Objective: Little is known about prognostic factors for lung squamous cell carcinoma (SCC). We aimed to explore radiologic and clinical factors affecting prognosis and to compare the prognosis of both central and peripheral lung SCCs. Materials and methods: Radiologic, clinical, and pathologic profiles of surgically confirmed SCCs from 382 patients were retrospectively reviewed. Tumor location, enhancement, necrosis, the presence of obstructive pneumonitis/atelectasis and underlying lung disease were evaluated on chest CT examination. Age, pulmonary function, tumor marker, and cancer stage were also assessed. Univariate and multivariate Cox regression analyses were performed to identify any correlation to overall survival (OS) and disease-free survival (DFS). Hazard rate estimation and competing risk analysis were done to evaluate recurrence pattern. Results: The median follow-up period was 56.2 months. Tumors were located centrally in 230 patients (60.2%) and peripherally in 152 patients (39.8%). Age (p = 0.002, hazard ratio [HR] 1.03, 95% confidence interval [CI] = [1.01, 1.06]) and interstitial lung abnormalities (ILAs) (p<0.001, HR 5.41, 95% CI = [3.08, 9.52]) were associated with poor OS on multivariate analysis. ILAs also had a strong association to DFS (p<0.001, HR 4.25, 95% CI = [3.08, 9.52]). Central cancers had two peaks of local recurrence development at 15 and 60 months after surgery, and peripheral tumors showed rising curves for metastasis development at 60 months. Conclusions: CT-determined ILAs are a strong biomarker predicting poor outcome. Prognosis may not vary according to tumor location, but the two groups exhibited different recurrence patterns. [ABSTRACT FROM AUTHOR]

Objective: To compare the magnetic resonance imaging (MRI) features of deep infiltrating endometriosis (DIE) lesions before and after pregnancy. Design: Retrospective study. Setting: A single French university tertiary referral hospital. Patients: Twenty-one women without a prior history of surgery for endometriosis with a radiological diagnosis by MRI with two sets of examinations performed before and after pregnancy. Interventions: The volumes of the lesions were compared using the same protocol before and after pregnancy based on MRI (1.5 T) examinations by a single experienced radiologist who is a referring practitioner for image-based diagnosis of endometriosis. Main outcome measure(s): The DIE lesion volume. Measurements and main results: Between October 2012 and December 2016, a total of 21 patients (67 lesions) were included and compared before and after pregnancy. The mean time interval between the MRI before pregnancy and delivery was 19.6 ± 8.5 months (median: 17.6, IQR 13.5–25.2 months). The mean time interval between delivery and the MRI after pregnancy was 11.0 ± 6.4 months (median: 8.3, IQR 6–15.2 months). The mean overall DIE lesion volume by MRI was significantly higher before pregnancy compared to after pregnancy (2,552 ± 3,315 mm3 vs. 1,708 ± 3,266 mm3, respectively, p < 0.01). The mean volume by MRI of the largest lesion of each patient was significantly higher before pregnancy compared to after pregnancy (4,728 ± 4,776 mm3 vs. 3165 ± 5299 mm3; p < 0.01). Conclusion: Our data indicate a favorable impact of pregnancy on DIE lesion volumes as measured by MRI. [ABSTRACT FROM AUTHOR]

Purpose: The effects of gravity on bevacizumab or the recommended head position after intraocular bevacizumab injection have not been reported. To evaluate the effect of gravity on bevacizumab in vitro, we added bevacizumab to the upper part of a test tube filled with balanced salt solution (BSS) and examined its distribution over time. Materials and methods: Sixty-four test tubes were divided equally into two groups; group 1 (32, collected from upper part of the tube) and group 2 (32, collected from lower part of the tube). Each test tube was filled with 5 mL BSS before bevacizumab (1.25 mg/0.05 mL) was added, and then stored at 36°C. Bevacizumab concentration in 8 test tubes from each group was measured at 12, 24, 48, and 168 h using an enzyme-linked immunosorbent analysis (ELISA) kit. Mann–Whitney and Jonckheere–Terpstra tests were used for statistical analysis. Results: Bevacizumab concentration was significantly higher in Group 2 than in Group 1 at 12, 24, 48, and 168 h (12, 24, 48, and 168 h; P < 0.01 each; Mann–Whitney test). The mean change in bevacizumab concentration over time tended to increase in Group 1 (P < 0.01; Jonckheere–Terpstra test), but tended to decrease in Group 2 (P < 0.01; Jonckheere–Terpstra test). Conclusions: The significant differences in concentration between the upper and lower parts even after a considerable amount of storage time showed that bevacizumab did not dissolve immediately and diffused evenly throughout the solution. It appeared that more bevacizumab settled in the lower part of the tube than in the upper part because of gravitational force. However, the concentration difference between the upper and lower parts decreased as bevacizumab gradually diffused over time, indicating that the difference in concentration due to gravity was more significant at the beginning of bevacizumab injection. [ABSTRACT FROM AUTHOR]

Echocardiography, as a noninvasive hemodynamic evaluation technique, is frequently used in critically ill patients. Different opinions exist regarding whether it can be interchanged with traditional invasive means, such as the pulmonary artery catheter thermodilution (TD) technique. This systematic review aimed to analyze the consistency and interchangeability of cardiac output measurements by ultrasound (US) and TD. Five electronic databases were searched for studies including clinical trials conducted up to June 2019 in which patients’ cardiac output was measured by ultrasound techniques (echocardiography) and TD. The methodological quality of the included studies was evaluated by two independent reviewers who used the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2), which was tailored according to our systematic review in Review Manager 5.3. A total of 68 studies with 1996 patients were identified as eligible. Meta-analysis and subgroup analysis were used to compare the cardiac output (CO) measured using the different types of echocardiography and different sites of Doppler use with TD. No significant differences were found between US and TD (random effects model: mean difference [MD], -0.14; 95% confidence interval, -0.30 to 0.02; P = 0.08). No significant differences were observed in the subgroup analyses using different types of echocardiography and different sites except for ascending aorta (AA) (random effects model: mean difference [MD], -0.37; 95% confidence interval, -0.74 to -0.01; P = 0.05) of Doppler use. The median of bias and limits of agreement were -0.12 and ±0.94 L/min, respectively; the median of correlation coefficient was 0.827 (range, 0.140–0.998). Although the difference in CO between echocardiography by different types or sites and TD was not entirely consistent, the overall effect of meta-analysis showed that no significant differences were observed between US and TD. The techniques may be interchangeable under certain conditions. [ABSTRACT FROM AUTHOR]

Background: The Pregnane X Receptor (PXR) is a principal signal transducer in mucosal responses to xenobiotic stress. It is well-recognized that inflammatory bowel disease is accompanied by xenobiotic stress, but the importance of the PXR in limiting inflammatory responses in inflammatory bowel disease remains obscure at best. Methods: We stimulate a total of 106 colonic biopsies from 19 Crohn’s disease patients with active disease, 36 colonic biopsies from 8 control patients, colonic organoids and various cell culture models (either proficient or genetically deficient with respect to PXR) in vitro with the PXR ligand rifampicin or vehicle. Effects on NF-κB activity are assessed by measuring interleukin-8 (IL-8) and interleukin-1ß (IL-1ß) mRNA levels by qPCR and in cell culture models by NF-κB reporter-driven luciferase activity and Western blot for signal transduction elements. Results: We observe a strict inverse correlation between colonic epithelial PXR levels and NF-κB target gene expression in colonic biopsies from Crohn’s disease patients. PXR, activated by rifampicin, is rate-limiting for mucosal NF-κB activation in IBD. The correlation between colonic epithelial PXR levels and NF-κB target gene expression was also observed in intestinal organoids system. Furthermore, in preclinical in vitro models of intestinal inflammation, including intestinal organoids, genetic inactivation of PXR unleashes NF-κB-dependent signal transduction whereas conversely NF-κB signaling reduces levels of PXR expression. Conclusions: Our data indicate that the PXR is a major and clinically relevant antagonist of NF-κB activity in the intestinal epithelial compartment during inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis and acute myocardial infarction (AMI) present dilemma whether dual antiplatelet therapy (DAPT) should be used. Methods: Electronic medical records between 2001–2013 were retrieved from Taiwan National Health Insurance Research Database. Patients were excluded for missing information, age <20 years old, history of AMI, liver transplant, autoimmune disease, coagulopathy, taking DAPT 3 months before index date, follow-up <3 months, anticoagulation user, without DAPT, and events of myocardial infarction (MI), ischemic stroke, major bleeding, and heart failure within 3-month of enrollment. Primary outcomes were 1-year all-cause mortality, recurrent MI, major bleeding, and gastrointestinal bleeding. Results: A total of 150,887 patients with AMI retrieved. After exclusion criteria and propensity score-matching, 914 cirrhotic and 3,656 non-cirrhotic patients with AMI on DAPT were studied. During 1-year follow-up, there was significantly increased mortality in cirrhotic patients compared to non-cirrhotic patients (HR = 1.49, 95% CI = 1.28–1.74). There was significantly decreased recurrent MI in cirrhotic patients compared to non-cirrhotic patients (subdistribution HR [SHR] = 0.71, 95% CI = 0.54–0.92). However, non-significantly increased major bleeding (SHR = 1.23, 95% CI = 0.87–1.73) and significantly increased gastrointestinal bleeding (SHR = 1.49, 95% CI = 1.31–1.70). Conclusions: In cirrhotic patients with AMI, DAPT offers benefit with decreased recurrent MI at the expense of increased gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Trauma and hemorrhagic shock can lead to acute traumatic coagulopathy (ATC) that is not fully reversed by prehospital resuscitation as simulated with a limited volume of fresh whole blood (FWB) in a rat model. Tranexamic Acid (TXA) is used as an anti-fibrinolytic agent to reduce surgical bleeding if administered prior to or during surgery, and to improve survival in trauma if given early after trauma. It is not clear from the existing clinical literature whether TXA has the same mechanism of action in both settings. This study sought to explore the molecular mechanisms of TXA activity in trauma and determine whether administration of TXA as a supplement to FWB resuscitation could attenuate the established ATC in a rat model simulating prehospital resuscitation of polytrauma and hemorrhagic shock. In a parallel in-vitro study, the effects on clotting assays of adding plasmin at varying doses along with either simultaneous addition of TXA or pre-incubation with TXA were measured, and the results suggested that maximum anti-fibrinolytic effect of TXA on plasmin-induced fibrinolysis required pre-incubation of TXA and plasmin prior to clot initiation. In the rat model, ATC was induced by polytrauma followed by 40% hemorrhage. One hour after trauma, the rats were resuscitated with FWB collected from donor rats. Vehicle or TXA (10mg/kg) was given as bolus either before trauma (TXA-BT), or 45min after trauma prior to resuscitation (TXA-AT). The TXA-BT group was included to contrast the coagulation effects of TXA when used as it is in elective surgery vs. what is actually feasible in real trauma patients (TXA-AT group). A single dose of TXA prior to trauma significantly delayed the onset of ATC from 30min to 120min after trauma as measured by a rise in prothrombin time (PT). The plasma d-dimer as well as plasminogen/fibrinogen ratio in traumatized liver of TXA-BT were significantly lower as compared to vehicle and TXA-AT. Wet/dry weight ratio and leukocytes infiltration of lungs were significantly decreased only if TXA was administrated later, prior to resuscitation (TXA-AT). In conclusion: Limited prehospital trauma resuscitation that includes FWB and TXA may not correct established systemic ATC, but rather may improve overall outcomes of resuscitation by attenuation of acute lung injury. By contrast, TXA given prior to trauma reduced levels of fibrinolysis at the site of tissue injury and circulatory d-dimer, and delayed development of coagulopathy independent of reduction of fibrinogen levels following trauma. These findings highlight the importance of early administration of TXA in trauma, and suggest that further optimization of dosing protocols in trauma to exploit TXA’s various sites and modes of action may further improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background & aims: Previous studies from western countries have reported that active hepatocellular carcinoma (HCC) was associated with direct-acting antiviral (DAA) treatment failure. We sought to examine this issue in an Asian cohort. Methods: A retrospective cohort study was conducted on hepatitis C virus (HCV)-infected patients with advanced fibrosis who were treated with DAAs at our hospital between January 2017 and June 2018. Results: We treated 1021 HCV-infected patients during this period. A total of 976 of those patients were enrolled in a per-protocol analysis, including 556 (57.2%) who had genotype 1b infections, and 314 (32.3%) who had genotype 2 infections. The mean age of all 976 patients was 65.5 years, and 44.5% were male. 781 of the patients had no HCC, 172 had inactive HCC, and 23 had active HCC. Non-sustained virologic response (SVR) was noted in 10 (1.3%) patients without HCC, 5 (2.9%) patients with inactive HCC, and 4 (13.0%) patients with active HCC. After adjustment for confounders, active HCC (versus inactive HCC and non-HCC) was associated with non-SVR (adjusted odds ratio [AOR] = 24.5 (95% confidence interval [CI] = 4.4–136.9), P<0.001). Next, we excluded the 23 patients with active HCC from the multivariate analysis. After adjustment for confounders, inactive HCC (versus non-HCC) was not associated with non-SVR (AOR = 3.1 (95% CI = 0.94–9.95), P = 0.06). Conclusion: Active HCC was associated with non-SVR, while inactive HCC was not. We thus suggest the deferral of DAA treatment until after the complete radiological response of HCCs to treatment. [ABSTRACT FROM AUTHOR]

Cognitive impairments are a common consequence of traumatic brain injury (TBI). The hippocampus is a subcortical structure that plays a key role in the formation of declarative memories and is highly vulnerable to TBI. The α7 nicotinic acetylcholine receptor (nAChR) is highly expressed in the hippocampus and reduced expression and function of this receptor are linked with cognitive impairments in Alzheimer’s disease and schizophrenia. Positive allosteric modulation of α7 nAChRs with AVL-3288 enhances receptor currents and improves cognitive functioning in naïve animals and healthy human subjects. Therefore, we hypothesized that targeting the α7 nAChR with the positive allosteric modulator AVL-3288 would enhance cognitive functioning in the chronic recovery period of TBI. To test this hypothesis, adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury or sham surgery. At 3 months after recovery, animals were treated with vehicle or AVL-3288 at 30 min prior to cue and contextual fear conditioning and the water maze task. Treatment of TBI animals with AVL-3288 rescued learning and memory deficits in water maze retention and working memory. AVL-3288 treatment also improved cue and contextual fear memory when tested at 24 hr and 1 month after training, when TBI animals were treated acutely just during fear conditioning at 3 months post-TBI. Hippocampal atrophy but not cortical atrophy was reduced with AVL-3288 treatment in the chronic recovery phase of TBI. AVL-3288 application to acute hippocampal slices from animals at 3 months after TBI rescued basal synaptic transmission deficits and long-term potentiation (LTP) in area CA1. Our results demonstrate that AVL-3288 improves hippocampal synaptic plasticity, and learning and memory performance after TBI in the chronic recovery period. Enhancing cholinergic transmission through positive allosteric modulation of the α7 nAChR may be a novel therapeutic to improve cognition after TBI. [ABSTRACT FROM AUTHOR]

Background: Linezolid has shown strong antimicrobial activity against multidrug-resistant (MDR)/rifampin-resistant strains of Mycobacterium tuberculosis. Linezolid achieves clinical efficacy mainly through area under the concentration time curve/minimum inhibitory concentration ratio in the infected lesion site. Previous studies mainly focused on the relationship between linezolid concentrations in the blood and infected bone tissue when the blood drug concentration reached the peak 2 h after administration. However, we do not know whether linezolid can maintain the same bone/plasma ratio in infected bone tissue when the blood concentration reaches the trough level. Therefore, this study aimed to evaluate the penetrability of linezolid into bone tissue 24 h after administration in patients with MDR spinal tuberculosis (TB). Methods: Nine MDR spinal TB patients, who received a treatment regimen including linezolid and underwent surgery, were enrolled prospectively from April 2017 to March 2019. Blood and diseased bone tissue specimens were collected simultaneously during operations 24 h after taking 600 mg of linezolid orally. Linezolid concentrations in plasma and diseased bone tissue specimens were determined by high-performance liquid chromatography–tandem mass spectrometry. Results: Following a 600 mg oral administration of linezolid 24 h before surgery, median concentrations of linezolid in plasma and diseased bone tissue for the 9 patients were 1.98 mg/L (range 0.30–3.44 mg/L) and 0.60 mg/L (range 0.18–2.13 mg/L), respectively, at resection time. The median diseased bone/plasma linezolid concentration ratio was 0.48 (range 0.30–0.67). Pearson’s correlation analysis showed that linezolid concentrations in the plasma were positively related to those in diseased bone tissue (r = 0.949, p < 0.001). Conclusions: After 24 h of medication, linezolid still had good penetrability into diseased bone tissue in patients with MDR spinal TB. [ABSTRACT FROM AUTHOR]

Background: Personalized medicine requires accurate molecular profiling for targeted therapy decisions. Insufficient tissue yield or tumor heterogeneity frequently limits the correct tissue biomarker determination. As a noninvasive complement to traditional tissue biopsies, liquid biopsies detect and track cancer driver mutations from biofluids (e.g., blood, urine). Here we present the analytical validation of Target Selector™ ctDNA assays capable of single mutant DNA copy detection. Methods: The Target Selector ctDNA assay applies a patented Switch-Blocker technology to suppress amplification of background (wild-type) WT alleles, while allowing specific amplification of very low frequency mutant alleles. In contrast to allele specific enrichment technologies like ddPCR, one Switch-Blocker inhibits amplification of a DNA target up to 15 bp in length (e.g., one Switch-Blocker covers all KRAS exon 2, codon 12 and 13 variants). Target enrichment is achieved through a quantitative PCR reaction; subsequent DNA sequencing confirms mutation identity. Analytical validation with cancer cell line DNA was conducted by three independent operators using five instruments across five days. Results: A total of 3086 samples were tested on EGFR, BRAF and KRAS Target Selector ctDNA assays, with EGFR WT as a reference. All assays showed >99% analytical sensitivity and specificity. Single mutant copy detection is confirmed by experimental data and theoretical estimates. In the presence of 14000 WT DNA copies, limits of detection were: EGFR Del19, 0.01%; EGFR L858R, 0.02%; EGFR T790M, 0.01%; BRAF V600E, 0.01%; KRAS G12C, 0.02%. Inter- and intra-assay analyses showed r2>0.94, suggesting consistent performance among operational variables. Healthy donor samples (100 tests) showed clinical specificity at >99%. Finally, Target Selector clinical experience data of >2200 patient samples is consistent with published tissue mutation prevalence. Conclusions: Highly sensitive Target Selector ctDNA assays with single mutant copy detection and limit of detection at 0.02% or better enable accurate molecular profiling vital for disease management. [ABSTRACT FROM AUTHOR]

The development of ICU-acquired sodium disturbances is not fully understood. Alterations in non-osmotic skin sodium storage, hypothetically inflammation-driven, could play a role. To investigate this in critically ill patients we conducted a patient-control study with skin punch biopsies in patients with sepsis (n = 15), after coronary artery bypass grafting (CABG, n = 15) and undergoing total hip arthroplasty (THA-controls, n = 15) respectively, together representing a range in severity of systemic inflammation. Biopsies were taken within 24 hours (sepsis) and within 2 hours (CABG) after ICU-admission, and prior to arthroplasty. Biopsies were analysed for sodium content. In addition immunostainings and quantitative real time PCR were performed. The primary aim of this study was to detect possible differences in amounts of cutaneous sodium. The secondary aims were to quantify inflammation and lymphangiogenesis with concomitant markers. The highest amounts of both water and sodium were found in patients with sepsis, with slightly lower values after CABG and the lowest amounts in THA-controls. Correlation between water and sodium was 0.5 (p<0.01). In skin biopsies in all groups comparable amounts of macrophages, T-cells and lymph vessels were found. In all groups comparable expression of inflammation markers were found. However, higher mRNA transcript expression levels of markers of lymphangiogenesis were found in patients with sepsis and after CABG. The conjoint accumulation of water and sodium points towards oedema formation. However, the correlation coefficient of 0.5 leaves room for alternative explanations, including non-osmotic sodium storage. No signs of dermal inflammation were found, but upregulation of markers of lymphangiogenesis could indicate future lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Background: Detection and pathology analysis of Mycobacterium leprae using skin biopsy tissues are essential for leprosy diagnosis and monitoring response to treatment. Although formalin fixation of patient tissues may not be ideal for molecular studies, biopsy samples are the most accessible material from suspected cases. Therefore, clinical molecular laboratories must be able to utilize formalin-fixed, paraffin-embedded (FFPE) material. Objective: To determine the best molecular method for diagnosing and monitoring leprosy in FFPE specimens, we developed a single-tube nested PCR (STNPCR) (131 bp) and SYBRGreen PCR (101 bp) assay using primers for the M. leprae-specific repetitive element (RLEP) gene and evaluated the results compared to those using previously established RLEP primers (372 bp). Methods: FFPE biopsy samples obtained from 145 leprosy patients (during or after multidrug therapy (MDT)) and patients with 29 other confounding dermatoses were examined by the bacteria index (BI) and by simple PCR, STNPCR, and SYBRGreen PCR using primers amplifying a 372-bp, 131-bp or 101-bp fragment of RLEP, respectively. Results: In leprosy patients receiving MDT, STNPCR showed a highest specificity of 100% and a positive predictive value (PPV) of 100%. For multibacillary (MB), paucibacillary (PB) and all leprosy patients, the highest sensitivities were 91.42%, 39.13%, and 67.92%, negative predictive values (NPVs) were 8.57%, 60.36%, and 32.07%, and the highest accuracies were 93.93%, 62.67%, and 74.81%, respectively, higher than the results of SYBRGreen PCR and simple PCR. For post-MDT leprosy patients, SYBRGreen PCR showed the highest sensitivity of 50.0%, highest specificity of 100%, a PPV of 100%, an NPV of 100% and the highest accuracy of 83.72% for MB patients, which were higher than those of STNPCR and simple PCR. STNPCR showed the highest sensitivity of 26.66% and 34.48%, highest specificity of 100% and 100%, a PPV of 100% and 100%, NPV of 72.50% and 60.21%, and highest accuracy of 75.00% and 67.24% for PB and leprosy patients, respectively, higher than those of SYBRGreen PCR and simple PCR. Conclusions: These findings suggest that STNPCR or SYBRGreen PCR (131-bp and 101-bp fragment amplification, respectively) for RLEP using FFPE specimens performs better as a diagnostic test and for monitoring response to MDT than does simple PCR based on 372-bp fragment amplification. Additionally, STNPCR showed increased sensitivity for PB diagnosis using FFPE specimens, which can be transferred remotely or retrieved from previous leprosy patients. [ABSTRACT FROM AUTHOR]

Background: Cancers of the head and neck have a high mortality rate, and roughly 10% of the patients die within six months of diagnosis. To our knowledge little has been written about this group. We wished to identify risk factors for early death, to predict and monitor patients at risk better and, if possible, avoid unjustified major treatment. Methods and findings: This population-based nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included data from 2008–2015 and 9733 patients at potential risk of early death. A total of 925 (9.5%) patients died within six months. For every year older the patients became, the risk of early death increased by 2.3% (p<0.001). The relative risk of death was 3.37 times higher (237%) for patients with WHO score 1 compared with WHO score 0. A primary tumour in the hypopharynx correlated with a 24% increased risk over the oral cavity (p<0.024). Patients with stage IV disease had a 3.7 times greater risk of early death than those with stage I (p<0.001). As expected, a 12 times increased risk of early death was noted in the palliative treatment group, compared to the curative group. Limitations to this study were that the actual cause of death was not recorded in the SweHNCR, and that socioeconomic factors, alcohol consumption, smoking habits, and HPV status, were not reported in SweHNCR until 2015. However, the fact that this is a population-based nationwide study including 9733 patients compensates for some of these limitations. Conclusions: Identification of patients at increased risk of early death shows that older patients with advanced disease, increased WHO score, primary tumour in the hypopharynx, and those given palliative treatment, are more likely than the others to die from head and neck cancer within six months of diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To identify risk factors associated with unfavorable outcomes in children with IgA vasculitis with nephritis (Henoch-Schőnlein purpura nephritis)(IgA-VN) Methods: PubMed, Embase, and Web of Science databases were searched for studies, published in English through February 2019. The data were extracted to perform pooled analysis, heterogeneity testing, subgroup analysis, sensitivity analysis, and publication bias analysis. Results: This meta-analysis showed that, older age at onset (WMD 1.77, 95% CI 0.35–3.18, p = 0.014), lower glomerular filtration rate (GFR; WMD -23.93, 95% CI -33.78- -14.09, p<0.0001), initial renal manifestations with nephrotic syndrome (OR 1.74, 95% CI 1.12–2.70, p = 0.013), with nephritic-nephrotic syndrome (OR 4.55, 95% CI 2.89–7.15, p<0.0001) and renal biopsy with crescentic nephritis (International Study of Kidney Disease in Children [ISKDC] grades III-V) (OR 3.85, 95% CI 2.37–6.28, p<0.0001) were significant risk factors associated with poor outcomes in IgA-VN, whereas initial clinical features with hematuria (OR 0.33, 95% CI 0.16–0.69, p = 0.003) and mild proteinuria±hematuria (OR 0.46, 95% CI 0.28–0.75, p<0.0001) were associated with progression to good outcomes. By contrast, gender, hypertension and initial renal manifestations of acute nephritic syndrome were not significantly associated with poor outcomes in IgA-VN. Conclusion: This meta-analysis showed that older age at onset, lower GFR, initial renal features of nephrotic syndrome and nephritic-nephrotic syndrome and renal biopsy with crescentic nephritis (ISKDC grades III-V) were predictive of poor prognosis in children with IgA-VN. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the results of endovascular therapy on the treatment of different types of iliac occlusions. Materials and methods: A bi-center prospective, non-randomized study was conducted on 100 patients (mean age 59.14 ± 8.53; 64 men) who underwent endovascular treatment of iliac occlusive disease between January 2013 and November 2017. We evaluated baseline data, procedure, and follow-up results for the entire group, and according to Trans-Atlantic Inter-Society Consensus (TASC II) classification. The majority of patients (60%) were treated for severe claudication; 56 (56%) patients had TASC B occlusions, 28 patients TASC C, and 16 patients TASC D. Results: The mean length of the occluded segments was 61.41 ± 35.15 mm. Procedural complications developed in 6 patients (6%). Mean ankle-brachial pressure index increased from 0.40 ± 0.12 preoperatively to 0.82 ± 0.16 postoperatively. The mean follow-up was 33.18 ± 15.03 months. After 1 and 5 years, the primary patency rates were 98% and 75.1%, and the secondary patency rate was 97% respectively. Regarding occlusion complexity there were no statistical significant differences in primary patency rates (TASC B vs. C vs. D: p = 0.19). There were no statistically significant differences in primary patency rates between patients in different clinical stages, as well as between the type of stents, and location of the occlusion. Conclusion: In our study, endovascular treatment for iliac artery occlusions proved to be a safe and efficient approach with excellent primary and secondary patency rates regardless of the complexity of occlusions defined by TASC II classification. This study is aligned with the notion that in well selected patients, endovascular therapy can be the treatment of choice even in complex iliac lesions if performed by experienced endovascular interventionists in high volume centers. [ABSTRACT FROM AUTHOR]

Developing effective therapies for back pain associated with intervertebral disc (IVD) degeneration is a research priority since it is a major socioeconomic burden and current conservative and surgical treatments have limited success. Polyphenols are naturally occurring compounds in plant-derived foods and beverages, and evidence suggests dietary supplementation with select polyphenol preparations can modulate diverse neurological and painful disorders. This study tested whether supplementation with a select standardized Bioactive-Dietary-Polyphenol-Preparation (BDPP) may alleviate pain symptoms associated with IVD degeneration. Painful IVD degeneration was surgically induced in skeletally-mature rats by intradiscal saline injection into three consecutive lumbar IVDs. Injured rats were given normal or BDPP-supplemented drinking water. In-vivo hindpaw mechanical allodynia and IVD height were assessed weekly for 6 weeks following injury. Spinal column, dorsal-root-ganglion (DRG) and serum were collected at 1 and 6 weeks post-operative (post-op) for analyses of IVD-related mechanical and biological pathogenic processes. Dietary BDPP significantly alleviated the typical behavioral sensitivity associated with surgical procedures and IVD degeneration, but did not modulate IVD degeneration nor changes of pro-inflammatory cytokine levels in IVD. Gene expression analyses suggested BDPP might have an immunomodulatory effect in attenuating the expression of pro-inflammatory cytokines in DRGs. This study supports the idea that dietary supplementation with BDPP has potential to alleviate IVD degeneration-related pain, and further investigations are warranted to identify the mechanisms of action of dietary BDPP. [ABSTRACT FROM AUTHOR]

Aims: To stipulate a new definition for long-stay patients (LSPs) in pediatric intensive care unit (PICU). We defined LSPs as the 10% of patients with the longest PICU length-of-stay (LOS) for each age and diagnostic group. To assess whether the thresholds (days of PICU stay) for the definition of LSPs in PICU significantly differ among diagnostic and age categories. To determine whether independent associations exist between patients’ characteristics at admission and LSPs diagnosis in pre-specified diagnostic and age groups. Methods: This was a multicenter retrospective cohort study including all PICUs in Switzerland. Multivariable regression analysis was used to seek for association between patients’ variables at admission and LSPs Results: We included 22,284 patients with a median (IQR) age of 12 (1–84) months. Significantly different thresholds across diagnostic and age subgroups are identified. Readmission to PICU, higher PIM2 and NEMS (a score used to quantify nursing workload at intensive care unit level) at admission were associated with higher likelihood of becoming LSPs. Conclusions: Our results showed a significantly different definitions of LSPs for specific diagnoses and age categories. Readmission to PICU and higher acuity at admission are associated with longer PICU length-of-stay in the majority of diagnostic groups. A more personalized definition of LSPs in children based on actual patients’ characteristics should probably be used in an effort to optimize care and reduce costs. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies evaluating the association between clinically diagnosed Alzheimer’s disease (AD) and age-related macular degeneration (AMD) have generated conflicting results. This study is the first to assess whether AMD prevalence is higher in AD patients than non-AD controls by using histopathology to definitively diagnose AD. Methods: This was a retrospective case-control study utilizing diagnostic information extracted from autopsy reports of patients age 75 and above, including 115 with a neuropathological diagnosis of AD and 57 age-matched normal controls. Results: The rate of AMD was not significantly higher in AD cases (53.0%) than in controls (59.6%) (z = 0.820, p = 0.794). AMD severity as determined by Sarks score was similar between AD patients and controls (χ2 = 2.96, p = 0.706). There was also no significant association between Braak stage of AD severity and AMD (χ2 = 4.55, p = 0.602). Discussion: No significant effect of AD diagnosis or pathologic severity on AMD comorbidity was found, suggesting that any shared mechanisms between AMD and AD may be nondeterministic. [ABSTRACT FROM AUTHOR]

Purpose: In 2013, the American Society for Radiation Oncology (ASTRO) issued a Choosing Wisely recommendation against the routine use of intensity modulated radiotherapy (IMRT) for whole breast irradiation. We evaluated IMRT use and subsequent impact on Medicare expenditure in the period immediately preceding this recommendation to provide a baseline measure of IMRT use and associated cost consequences. Methods and materials: SEER records for women ≥66 years with first primary diagnosis of Stage I/II breast cancer (2008–2011) were linked with Medicare claims (2007–2012). Eligibility criteria included lumpectomy within 6 months of diagnosis and radiotherapy within 6 months of lumpectomy. We evaluated IMRT versus conventional radiotherapy (cRT) use overall and by SEER registry (12 sites). We used generalized estimating equations logit models to explore adjusted odds ratios (OR) for associations between clinical, sociodemographic, and health services characteristics and IMRT use. Mean costs were calculated from Medicare allowable costs in the year after diagnosis. Results: Among 13,037 women, mean age was 74.4, 50.5% had left-sided breast cancer, and 19.8% received IMRT. IMRT use varied from 0% to 52% across SEER registries. In multivariable analysis, left-sided breast cancer (OR 1.75), living in a big metropolitan area (OR 2.39), living in a census tract with ≤$90,000 median income (OR 1.75), neutral or favorable local coverage determination (OR 3.86, 1.72, respectively), and free-standing treatment facility (OR 3.49) were associated with receipt of IMRT (p<0.001). Mean expenditure in the year after diagnosis was $8,499 greater (p<0.001) among women receiving IMRT versus cRT. Conclusion: We found highly variable use of IMRT and higher expenditure in the year after diagnosis among women treated with IMRT (vs. cRT) with early-stage breast cancer and Medicare insurance. Our findings suggest a considerable opportunity to reduce treatment variation and cost of care while improving alignment between practice and clinical guidelines. [ABSTRACT FROM AUTHOR]

Background: Large cell neuroendocrine carcinoma (LCNEC) is a rare and typically aggressive malignancy with poor prognosis. This study developed a nomogram model to predict the overall survival (OS) of patients with LCNEC. Methods: LCNEC patients were identified from the Surveillance, Epidemiology, and End Results database between 2004–2014. Univariate and multivariate Cox regression models were used to determine demographic and clinicopathological features associated with OS. A nomogram model was generated to predict OS and its performance was assessed by Harrell’s concordance index (C-index), calibration plots, and subgroup analysis by risk scores. Results: Of 3048 eligible patients with LCNEC, 2138 were randomly grouped into the training set and 910 into the validation set. Age at diagnosis, gender, tumor stage, N stage, tumor size, and surgery of primary site were independent prognostic factors of OS. C-index values of the nomogram were 0.75 (95% CI, 0.74–0.76) and 0.76 (95% CI, 0.74–0.77) in the training and validation sets, respectively. In both cohorts, the calibration plots showed good concordance between the predicted and observed OS at 3 and 5 years. Kaplan-Meier curves revealed significant differences in OS in patients stratified by nomogram-based risk score, and patients with a higher-than-median risk score had poorer OS. Conclusion: This is the first nomogram developed and validated in a large population-based cohort for predicting OS in patients with LCNEC, and it shows favorable discrimination and calibration abilities. Use of this proposed nomogram has the potential to improve prediction of survival risk, and lead to individualized clinical decisions for LCNEC. [ABSTRACT FROM AUTHOR]

Lymphovascular space invasion (LVSI) is considered to be the beginning of lymphogenous and hematogenous metastases. It is strongly related to dissemination, and therefore could be a valuable predictive sign of lymph node metastases and distant spread. Recently, the presence of LVSI in endometrial cancer (EC) has been shown to be an independent prognostic factor. The preoperative diagnosis of LVSI by pathological examination is difficult and LVSI is detected after surgery. The aim of the current study was to explore candidate genes as potential diagnostic biomarkers and determine whether they are predictors of LVSI in patients with EC. A total of 88 surgical specimens obtained from EC patients who had undergone surgical resection at Fukushima Medical University Hospital between 2010 and 2015 were analyzed using DNA microarray. LVSI was significantly associated with poor prognostic factors in EC such as higher tumor grade, lymph node metastasis, deep myometrium invasion, advanced stage and recurrence. Fifty-five candidate genes were significantly differentially expressed between 26 LVSI-positive and 62 LVSI-negative samples. All 88 samples were divided into two groups according to hierarchical clustering of 55 genes. Regarding diagnostic accuracy, sensitivity and negative predictive value were both high (92% and 95%, respectively); further, specificity and positive predictive value were both moderate (63% and 71%, respectively). Our data suggests that the 55-gene signature could contribute to predicting LVSI in EC, and provide clinically important information for better management. The molecular signatures of 55 genes may be also useful for understanding the underlying mechanism of LVSI. [ABSTRACT FROM AUTHOR]

Chronic/abnormal activation of endoplasmic reticulum (ER) stress is linked to the exacerbation of the inflammatory process and has been recently linked to Crohn’s disease (CD) pathophysiology. We investigated the intestinal mucosa and the mesenteric adipose tissue (MAT) collected from CD patients with active disease (CD group) and from non-IBD patients (CTR group) to study ER stress activation and to address tissue-specific modulation in CD. The intestinal mucosa of CD patients showed an upregulation in the expression of ER stress related genes, including ATF3, DNAJC3, STC2, DDIT3, CALR, HSPA5 and HSP90B1. Results showed that EIF2AK3 gene was upregulated, along with increased protein expression of p-eIF2α and p-eIF2α/eIF2α ratio. Additionally, ERN1 gene expression was upregulated, along with an increased spliced/activated form sXBP1 protein. Despite the upregulation of ATF6 gene expression in the intestinal mucosa of CD patients, no differences were found in ATF6 protein expression. Lastly, the analysis of MAT revealed unchanged levels of ER stress markers along with no differences in the activation of UPR. However, chaperone gene expression was modulated in the MAT of CD patients. To conclude, our results address tissue-specific differences in UPR activation in CD and point the ER stress as an important pro-inflammatory mechanism in CD, specifically in the intestinal mucosa. [ABSTRACT FROM AUTHOR]

Variceal hemorrhage may cause high rebleeding and mortality rates. Preventing the first episode of variceal bleeding is mandatory in patients with high-risk esophageal varices (EV). This study aimed to identify factors that predict the recurrence of EV after endoscopic treatment (ET), and to develop a reasonable therapeutic strategy for EV in cirrhosis. From January 2012 to December 2014, 45 patients with cirrhosis and high-risk EV underwent ET, including sclerotherapy and/or ligation. Statistical analyses identified factors associated with the recurrence of EV after ET, and the Kaplan-Meier method determined the cumulative variceal recurrence rates. The 1-, 2-, and 3-year cumulative posttreatment recurrence rates for EV were 13.3%, 29.5%, and 32.2%, respectively. No significant differences were evident between the patients with and without variceal recurrences at 1-year posttreatment. The multivariate regression analyses identified a history of partial splenic embolization (PSE) and the pretreatment Child-Pugh classification as independent predictors of variceal recurrences at 2 years (p < 0.05) and 3 years (p < 0.05) posttreatment. While EV did not recur after ET and splenic artery embolization in cases with Child-Pugh class A, the overall posttreatment variceal recurrence rates were 0% and 66.7% when PSE was performed before and after ET, respectively, in those with Child-Pugh class B or C. Splenic artery embolization significantly reduced the hepatic venous pressure gradient and markedly lowered the Child-Pugh score in 15 patients. Adjunctive PSE and pretreatment Child-Pugh class A could be independently associated with reduced cumulative recurrence rates of EV post-ET. From the perspectives of portal hemodynamics and hepatic function, splenic artery embolization before or after ET could prevent posttreatment variceal recurrence in patients with Child-Pugh class A, and PSE before ET could achieve the long-term eradication of EV following ET in those with Child-Pugh class B or C. [ABSTRACT FROM AUTHOR]

Purpose: To investigate cerebral microstructural alterations in patients treated with calcineurin inhibitors (CNI) after orthotopic liver transplantation (OLT) using quantitative magnetic resonance imaging (qMRI) and a cross-sectional study design. Methods: Cerebral qMRI was performed in 85 patients in a median 10 years after OLT compared to 31 healthy controls. Patients were treated with different dosages of CNI or with a CNI-free immunosuppression (CNI-free: n = 19; CNI-low: n = 36; CNI-standard: n = 30). T2-, T2*- and T2’- relaxation times, as well as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were measured in brain gray and white matter by using the regions of interest method. Results: In comparison to controls, patients revealed significantly increased T2, T2*, T2’, ADC and reduced FA, predominantly in the frontal white matter, indicating microstructural brain alterations represented by increased free water (increased T2), reduced neuronal metabolism (increased T2’) and a lower degree of spatial organization of the nervous fibers (reduced FA). CNI-low and CNI-free patients showed more alterations than CNI-standard patients. Analysis of their history revealed impairment of kidney function while under standard CNI dose suggesting that these patients may be more vulnerable to toxic CNI side-effects. Conclusion: Our findings suggest that the individual sensitivity to toxic side effects should be considered when choosing an appropriate immunosuppressive regimen in patients after liver transplantation. [ABSTRACT FROM AUTHOR]

Objective: To analyze and compare the performance of the Simplified-Acute-Physiology-Score (SAPS) 2 and SAPS 3 among intermediate care patients with internal disorders. Materials and methods: We conducted a retrospective single-center analysis in patients (n = 305) admitted to an intermediate-care-unit (ImCU) for internal medicine at the University Hospital Essen, Germany. We employed and compared the SAPS 2 vs. the SAPS 3 scoring system for the assessment of disease severity and prediction of mortality rates among patients admitted to the ImCU within an 18-month period. Both scores, which utilize parameters recorded at admission to the intensive-care-unit (ICU), represent the most widely applied scoring systems in European intensive care medicine. The area-under-the-receiver-operating-characteristic-curve (AUROC) was used to evaluate the SAPS 2 and SAPS 3 discrimination performance. Ultimately, standardized-mortality-ratios (SMRs) were calculated alongside their respective 95%-confidence-intervals (95% CI) in order to determine the observed-to-expected death ratio and calibration belt plots were generated to evaluate the SAPS 2 and SAPS 3 calibration performance. Results: Both scores provided acceptable discrimination performance, i.e., the AUROC was 0.71 (95% CI, 0.65–0.77) for SAPS 2 and 0.77 (95% CI, 0.72–0.82) for SAPS 3. Against the observed in-hospital mortality of 30.2%, SAPS 2 showed a weak performance with a predicted mortality of 17.4% and a SMR of 1.74 (95% CI, 1.38–2.09), especially in association with liver diseases and/or sepsis. SAPS 3 performed accurately, resulting in a predicted mortality of 29.9% and a SMR of 1.01 (95% CI, 0.8–1.21). Based on Calibration belt plots, SAPS 2 showed a poor calibration-performance especially in patients with low mortality risk (P<0.001), while SAPS 3 exhibited a highly accurate calibration performance (P = 0.906) across all risk levels. Conclusions: In our study, the SAPS 3 exhibited high accuracy in prediction of mortality in ImCU patients with internal disorders. In contrast, the SAPS 2 underestimated mortality particularly in patients with liver diseases and sepsis. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve implantation (TAVI) is an option for treatment for patients with severe aortic stenosis who are at high risk for death with surgical aortic valve replacement (SAVR). It is unknown whether TAVI can be safely introduced to intermediate- and low-risk patients. Objective: To compare the efficacy and safety of TAVI and SAVR in patients with intermediate- and low-surgical risk. Data sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to April 15, 2019. Study selection: We included randomized controlled trials comparing TAVI with SAVR in patients with intermediate- and low-surgical risk. Data extraction: Meta-analyses were conducted using random-effects models to calculate risk ratios (RR) with corresponding 95% confidence interval (CI). Two independent reviewers completed citation screening, data abstraction, and risk assessment. Primary outcome was a composite of all-cause mortality or disabling stroke at 12 months. Data Synthesis: A total of 5 trials randomizing 6390 patients were included. In patients with low risk, TAVI was associated with a significant reduction in the composite of all-cause mortality or disabling stroke compared with SAVR (RR, 0.56; 95%CI, 0.40–0.79; I2 = 0%). This benefit was not replicated in patients with intermediate risk (RR, 0.96; 95% CI, 0.80–1.15; I2 = 0%). Similar results were seen separately in all-cause mortality and disabling stroke when TAVI was compared with SAVR. Conclusion: For patients with severe aortic stenosis who were at low risk for death from surgery, TAVI achieved superior clinical outcomes compared to SAVR; however, these benefits were not seen in those with intermediate risk. This information may inform discussions about deciding between SAVR and TAVI for patients with low to intermediate risk separately. [ABSTRACT FROM AUTHOR]

Objective: The immune rejection mediated by CD4+ T cell and antigen presenting macrophages is the leading cause of corneal transplantation failure. Bone marrow-derived mesenchymal stem cells (BM-MSCs) possess robust immunomodulatory potentials, and have been shown by us and others to promote corneal allograft survival. However, the immunological mechanism underlying the protective effects of BM-MSCs remains unclear. Therefore, in the current study, this mechanism was investigated in a BM-MSC-treated rat model of corneal allograft rejection, in the hope to facilitate the search for novel interventional targets to corneal allograft rejection. Methods: Lewis rats were subjected to corneal transplantation and then received subconjunctival injections of BM-MSCs (2×106 cells / 100 μl PBS) immediately and at day 3 post-transplantation. The control group received the injections of PBS with the same volume. The clinical parameters of the corneal allografts, including opacity, edema, and neovascularization, were regularly evaluated after transplantation. On day 10 post-transplantation, the corneal allografts were collected and subjected to flow cytometry and high-throughput RNA sequencing (RNA-seq). GO enrichment and KEGG pathways were analyzed. The quantitative realtime PCR (qPCR) and immunohistochemistry (IHC) were employed to validate the expression of the selected target genes at transcript and protein levels, respectively. Results: BM-MSC subconjunctival administration prolonged the corneal allograft survival, with reduced opacity, alleviated edema, and diminished neovascularization. Flow cytometry showed reduced CD4+ T cells and CD68+ macrophages as well as boosted regulatory T cells (Tregs) in the BM-MSC-treated corneal allografts as compared with the PBS-treated counterparts. Moreover, the RNA-seq and qPCR results demonstrated that the transcript abundance of Cytotoxic T-Lymphocyte Associated Protein 4 (Ctla4), Protein Tyrosine Phosphatase, Receptor Type C (Ptprc), and C-X-C Motif Chemokine Ligand 9 (Cxcl9) genes were increased in the allografts of BM-MSC group compared with PBS group; whereas the expression of Heat Shock Protein Family A (Hsp70) Member 8 (Hspa8) gene was downregulated. The expression of these genes was confirmed by IHC at protein level. Conclusion: Subconjunctival injections of BM-MSCs promoted corneal allograft survival, reduced CD4+ and CD68+ cell infiltration, and enriched Treg population in the allografts. The BM-MSC-induced upregulation of Ctla4, Ptprc, Cxcl9 genes and downregulation of Hspa8 gene might contribute to the protective effects of BM-MSCs and subserve the potential interventional targets to corneal allograft rejection. [ABSTRACT FROM AUTHOR]

Background: Although many studies have compared birth-weight charts to determine which better identify infants at risk of adverse perinatal outcomes, less attention has been given to the threshold used to define small or large for gestational age (SGA or LGA) infants. Our aim was to explore different thresholds associated with increased risk of adverse perinatal outcomes using population, customised, and Intergrowth centile charts.Methods and Findings: This is a population-based cohort study (Swedish Medical Birth Registry), which included term singleton births between 2006 and 2015 from women with available data on first-trimester screening. Population, customised, and Intergrowth charts were studied. Outcomes included cesarean section, postpartum haemorrhage, severe perineal tear, Apgar score at 5 minutes, neonatal morbidity, and perinatal mortality. Odds for each outcome were assessed in intervals of 5 centiles of birth weight (reference being 40th-60th centiles) using logistic regression. Intervals of 5% of the population were also explored. Sensitivity for fixed false-positive rates (FPRs) was reported for neonatal outcomes. Data from 212,101 births were analysed. Mean age was 33 ± 5 years, 48% of women were nulliparous, and 80% were born in Sweden. Prevalence of SGA (<10th centile) was 10.1%, 10.0%, and 3.1%, and prevalence of LGA (>90th centile) was 10.0%, 8.2%, and 25.1%, assessed using population, customised, and Intergrowth charts, respectively. In small infants, the risk of perinatal mortality was consistently increased below the 15th, 10th, and 35th birth-weight centiles for the respective charts (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.05-2.39, p = 0.03 for 10th-15th population centile; OR 2.54, 95% CI 1.74-3.71, p < 0.001 for 5th-10th customised centile; OR 1.81, 95% CI 1.07-3.04, p = 0.03 for 30th-35th Intergrowth centile). The strength of association with adverse perinatal outcomes was different between infants below the 5th birth-weight centile for each chart (OR 4.47, 95% CI 3.30-6.04, p < 0.001 for the population chart; OR 5.78, 95% CI 4.22-7.91, p < 0.001 for the customised chart; OR 10.74, 95% CI 7.32-15.77, p < 0.001 for the Intergrowth chart) but similar in the smallest 5% of the population (OR 4.34, 95% CI 3.22-5.86, p < 0.001 for the population chart; OR 5.23, 95% CI 3.85-7.11, p < 0.001 for the customised chart; OR 4.69, 95% CI 3.47-6.34, p < 0.001 for the Intergrowth chart). For a fixed FPR of 10%, different thresholds for each chart achieved similar sensitivity for perinatal mortality in small infants (29% for all charts). Similar behaviour of different thresholds and similar risk/sensitivity for fixed FPR were observed in relation to other outcomes and for LGA infants. Limitations of this study include the relative homogeneity of the Swedish population, which limits generalisability to other populations; customised centiles may perform differently in populations with increased heterogeneity of ethnic background.Conclusions: The risk of adverse outcomes was consistent across proportions of the population but did not reflect fixed thresholds, such as the 10th or 90th centiles, across different growth charts. Chart-specific thresholds for the population should be considered in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Thrombophilic risk factors (TRFs) occur rather frequently in hemodialysis (HD) patients. However, little is known about their significance in HD patients, besides their potential impact on arteriovenous (AV) access failure, with varying results. We examined the effects of a wide variety of TRFs on both early AV fistula occlusion and survival among HD patients in long-term follow-up. Methods: In this single-center, observational study, 70 consecutive HD patients from our dialysis center were examined with respect to shunt occlusion within the first 2 years after fistula creation and patient survival in a long-term follow-up (at least 16 years). We examined the presence of factor V, prothrombin, and MTHFR mutations using real-time fluorescence polymerase chain reaction. Furthermore, antithrombin (AT), protein C, protein S, and antiphospholipid antibodies (APL-Abs) were assessed. Results: Among the 70 patients, 32 had MTHFR mutations, 10 had heterozygous factor V Leiden mutations, 4 had prothrombin mutations, 4 had protein S deficiency, 2 had protein C deficiency, 9 had AT deficiency, and 14 had APL-Abs. 40 patients had shunt occlusion. TRFs were associated with a significantly increased risk for shunt thrombosis (P<0.02). Kaplan–Meier analysis with a log-rank test revealed significantly shorter survival in HD patients with TRFs (P<0.02). Cox regression analysis showed that the presence of TRFs (P<0.05; hazard ratio, 1.94; 95% CI: 1.07–3.56), but not early shunt occlusion, was associated with short patient survival. Conclusions: TRFs in hemodialysis patients have a strong impact on patient survival and early AV fistula failure; however, patient survival is not significantly affected by early shunt occlusion. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the prevalence and clinical consequences of occult intra-operative periprosthetic femoral fractures in total hip arthroplasty (THA). Between 2012 and 2017, a total of 113 primary THAs were enrolled. The mean age of the patients was 66.4 ± 7.6 years. We assessed occult intra-operative periprosthetic femoral fractures with the use of computed tomography (CT) and risk factors, including age, sex, body mass index, diagnosis, stem size, and radiographic parameters of proximal femoral geometry were analyzed. We also assessed the differences in thigh pain and stem subsidence and alignment between the patients with and without occult periprosthetic femoral fracture. Occult intra-operative periprosthetic femoral fractures were found in 13 of 113 hips (11.5%). In 9/13 (69.2%) of occult fractures, fracture lines were started from the region below the tip of the lesser trochanter. Six periprosthetic femoral fractures (5.3%) were found during the operation. Out of the five hips that had detected femoral fractures around the lesser trochanter intra-operatively, four hips (80%) showed concurrent occult fractures on different levels. The female sex (P = .01) and canal filling ratio at 7 cm below the tip of the lesser trochanter (P = .01) were significantly different between the patients with and without occult periprosthetic femoral fracture. The sex was significantly associated with an increased risk in predicting an occult intra-operative periprosthetic femoral fracture (odds ratio of male, 0.25 compared with the female; 95% CI, 0.08–0.85; p = .02). There was a significant difference in the incidence of thigh pain between occult fracture group and non-occult fracture group (P < .05). There were no significant differences in stem subsidence and alignment between the patients with and without occult periprosthetic femoral fracture. All 13 cases of occult intra-operative periprosthetic femoral fractures were healed at the final follow-up. Occult periprosthetic femoral fractures are common during a long, trapezoidal, double-tapered cementless femoral stem fixation in primary THA, that CT scans are helpful to identify them, and that these fractures do not adversely affect the implant’s survival if a rigid fixation of the implants has been achieved. [ABSTRACT FROM AUTHOR]

Background & aims: Pulmonary arterial hypertension is a severe disease associated with frequent hospitalisations. This retrospective analysis of the French medical information PMSI-MSO database aimed to describe incident cases of patients with pulmonary arterial hypertension hospitalised in France in 2013 and to document associated hospitalisation costs from the national health insurance perspective. Methods: Cases of pulmonary arterial hypertension were identified using a diagnostic algorithm. All cases hospitalised in 2013 with no hospitalisation the previous two years were retained. All hospital stays during the year following the index hospitalisation were extracted, and classified as incident stays, monitoring stays or stays due to disease worsening. Costs were attributed from French national tariffs. Results: 384 patients in France were hospitalised with incident pulmonary arterial hypertension in 2013. Over the following twelve months, patients made 1,271 stays related to pulmonary arterial hypertension (415 incident stays, 604 monitoring stays and 252 worsening stays). Mean age was 59.6 years and 241 (62.8%) patients were women. Liver disease and connective tissue diseases were documented in 62 patients (16.1%) each. Thirty-one patients (8.1%) died during hospitalisation and four (1.0%) received a lung/heart-lung transplantation. The total annual cost of these hospitalisations was € 3,640,382. € 2,985,936 was attributable to standard tariffs (82.0%), € 463,325 to additional ICU stays (12.7%) and € 191,118 to expensive drugs (5.2%). The mean cost/stay was € 2,864, ranging from € 1,282 for monitoring stays to € 7,285 for worsening stays. Conclusions: Although pulmonary arterial hypertension is rare, it carries a high economic burden. [ABSTRACT FROM AUTHOR]

Purpose: Triple negative breast cancer (TNBC) patients frequently receive neoadjuvant chemotherapy (NAC). Only 50% will achieve pathological complete response (pCR). In this retrospective study, we evaluated TNBC outcomes with NAC vs. AC. Methods: Patients with stages II and III TNBC treated with NAC or AC between 2010 and 2013 were identified from the National Cancer Database. Baseline characteristics were compared with χ2 and two sample t tests. Kaplan-Meier survival analyses were computed in patients treated with NAC or AC, and log-rank tests used to examine differences. Unadjusted analyses of trends in proportions over time were performed using Cochran–Armitage tests. Log-binomial models were applied to estimate relative risks of non-pCR following NAC. Results: Of 19,151 patients, 5,621 (29.4%) received NAC, 13,530 (70.6%) received AC. NAC treated patients had worse OS compared to AC treated patients (73.4% vs. 76.8%; p<0.0001). pCR rate following NAC was 47.4%, and was associated with improved 5 year OS compared to non-pCR (86.2% vs. 62.3%; p<0.0001). In patients who received NAC, age, black race, clinical stage, diagnosis year, and Charlson-Deyo comorbidity score predicted non-pCR status. Use of NAC increased over the study period from 2010 to 2013 (27.8% - 31.2%; p = 0.0002). Conclusions: NAC may be inferior to AC in TNBC, likely related to the high frequency of non-pCR following NAC. It is unclear if removing the primary tumor prior to chemotherapy will have a beneficial biologic impact on therapeutic efficacy. These data should be considered hypothesis-generating as it is possible that the findings are due to selection bias, as physicians may use NAC for TNBC patients with more advanced local disease. Although, NAC still has a role in TNBC, developing biomarkers to identify patients likely to achieve pCR and benefit from NAC is an urgent need. [ABSTRACT FROM AUTHOR]

The bovine dry period is a non-lactating period between consecutive lactations characterized by mammary gland involution and redevelopment phases to replace senescent mammary epithelial cells with active cells primed for the next lactation. Dairy cows exposed to heat stress during the dry period experience milk yield reductions between 3–7.5 kg/d in the next lactation, partially attributed to processes associated with mammary cell growth and turnover during the dry period. However, the carry-over impact of dry period heat stress on mammary morphology during lactation has yet to be determined. In the current study, we hypothesized that exposure to heat stress during the dry period would alter alveolar microstructure and cellular turnover (i.e. proliferation and apoptosis) during lactation. Cows were either subjected to heat stress (HT, access to shade; n = 12) or cooling (CL, access to shade, fans, and soakers; n = 12) for a 46 d dry period. Upon calving, all cows were treated similarly with access to cooling for their entire lactation. Six cows per treatment were randomly selected for mammary gland biopsies at 14, 42, and 84 days in milk. Tissues were sectioned and stained for histological analysis. During lactation, HT cows produced 4 kg less colostrum and 3.7 kg less milk compared with CL cows. Lactating mammary gland microstructure was impacted after exposure to dry period heat stress; HT cows had fewer alveoli and a higher proportion of connective tissue in the mammary gland relative to CL cows, however alveolar area was similar between treatments. Rates of mammary epithelial cell proliferation and apoptosis were similar between treatment groups. This suggests that heat stress exposure during the dry period leads to reductions in milk yield that could be caused, in part, by a reduction in alveoli number in the lactating mammary gland but not to dynamic alterations in cellular turnover once lactation is established. [ABSTRACT FROM AUTHOR]

Background: There are limited data on acute kidney injury (AKI) complicating acute myocardial infarction with cardiogenic shock (AMI-CS). This study sought to evaluate 15-year national prevalence, temporal trends and outcomes of AKI with no need for hemodialysis (AKI-ND) and requiring hemodialysis (AKI-D) following AMI-CS. Methods: This was a retrospective cohort study from 2000–2014 from the National Inpatient Sample (20% stratified sample of all community hospitals in the United States). Adult patients (>18 years) admitted with a primary diagnosis of AMI and secondary diagnosis of CS were included. The primary outcome was in-hospital mortality in cohorts with no AKI, AKI-ND, and AKI-D. Secondary outcomes included predictors, resource utilization and disposition. Results: During this 15-year period, 440,257 admissions for AMI-CS were included, with AKI in 155,610 (35.3%) and hemodialysis use in 14,950 (3.4%). Older age, black race, non-private insurance, higher comorbidity, organ failure, and use of cardiac and non-cardiac organ support were associated with the AKI development and hemodialysis use. There was a 2.6-fold higher adjusted risk of developing AKI in 2014 compared to 2000. Presence of AKI-ND and AKI-D was associated with a 1.3 and 1.7-fold higher adjusted risk of mortality. Compared to the cohort without AKI, AKI-ND and AKI-D were associated with longer length of stay (9±10, 12±13, and 18±19 days respectively; p<0.001) and higher hospitalization costs ($101,859±116,204, $159,804±190,766, and $265,875 ± 254,919 respectively; p<0.001). Conclusion: AKI-ND and AKI-D are associated with higher in-hospital mortality and resource utilization in AMI-CS. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the value of contrast-enhanced ultrasound (CEUS) for preoperative assessment of liver reserve function in patients with liver tumors. The indocyanine green (ICG) clearance tests and CEUS examinations of 45 noncirrhotic patients with liver tumors were performed prior to liver resection. Parameters time to peak (TtoPk), arrival time (Atm) as well as perfusion parameters A, k and A x k were generated from time-intensity curve (TIC) of CEUS. The correlation analyses of the ICG clearance per unit time (ICGK) and the retention rate at 15 min (ICGR15) with TtoPk, Atm, A, k and A x k were performed, and the diagnostic ability as well as optimal cut-off values of TtoPk and Atm for differentiating patients with ICGR15>10% from ICGR15<10% were analyzed. There were significant correlations of ICGK with TtoPk and Atm, and the correlation coefficients were 0.363 (p = 0.014) and -0.482 (p = 0.001), respectively. Significant correlations of ICGR15 with TtoPk and Atm were revealed, and the correlation coefficients were -0.416 (p = 0.004) and 0.303 (p = 0.043), respectively. No correlation of ICGK or ICGR15 with A, k and A x k was found in this study. There were significant differences in TtoPk and Atm between patients with ICGR15>10% and ICGR15<10% (p = 0.028 and p = 0.026, respectively). TtoPk and Atm both had good diagnostic abilities in diagnosing patients with ICGR15>10% verusus ICGR15<10% (AUROC = 0.711 and 0.721, respectively). For ICGR15>10% vs ICGR15, the optimal cut-off values of TtoPk and Atm were 13.307 s and 11.007 s, respectively, while the sensitivity and specificity were 75.0% and 72.7%, 60.6% and 75.0%, respectively. This study revealed that CEUS has the potential to be a new method to evaluate the liver reserve function of patients. With the optimal cut-off values of TtoPk and Atm, qualitative assessment of patients with ICGR15>10% could be more easily achieved by CEUS with good diagnostic abilities. [ABSTRACT FROM AUTHOR]

Introduction: End-stage renal disease (ESRD) strongly associates with cardiovascular disease (CVD) risk. This risk is not completely mitigated by renal replacement therapy. Endothelial dysfunction (ED) and low-grade inflammation (LGI) may contribute to the increased CVD risk. However, data on serum biomarkers of ED and LGI during the transition to renal replacement therapy (dialysis and kidney transplantation) are scarce. Methods: We compared serum biomarkers of ED and LGI between 36 controls, 43 participants with chronic kidney disease (CKD) stage 5 non-dialysis (CKD5-ND), 20 participants with CKD stage 5 hemodialysis (CKD5-HD) and 14 participants with CKD stage 5 peritoneal dialysis (CKD5-PD). Further, in 34 and 15 participants repeated measurements were available during the first six months following dialysis initiation and kidney transplantation, respectively. Serum biomarkers of ED (sVCAM-1, E-selectin, P-selectin, thrombomodulin, sICAM-1, sICAM-3) and LGI (hs-CRP, SAA, IL-6, IL-8, TNF-α) were measured with a single- or multiplex array detection system based on electro-chemiluminescence technology. Results: In linear regression analyses adjusted for potential confounders, participants with ESRD had higher levels of most serum biomarkers of ED and LGI than controls. In addition, in CKD5-HD levels of serum biomarkers of ED and LGI were largely similar to those in CKD5-ND. In contrast, in CKD5-PD levels of biomarkers of ED were higher than in CKD5-ND and CKD5-HD. Similarly, in linear mixed model analyses sVCAM-1, thrombomodulin, sICAM-1 and sICAM-3 increased after PD initiation. In contrast, incident HD patients showed an increase in sVCAM-1, P-selectin and TNF-α, but a decline of hs-CRP, SAA and IL-6. Further, following kidney transplantation sVCAM-1, thrombomodulin, sICAM-3 and TNF-α were lower at three months post-transplantation and remained stable in the three months thereafter. Conclusions: Levels of serum biomarkers of ED and LGI were higher in ESRD as compared with controls. In addition, PD initiation and, less convincingly, HD initiation may increase levels of selected serum biomarkers of ED and LGI on top of uremia per se. In contrast to dialysis, several serum biomarkers of ED and LGI markedly declined following kidney transplantation. [ABSTRACT FROM AUTHOR]

The present study aimed to develop a denoising convolutional neural network metal artifact reduction hybrid reconstruction (DnCNN-MARHR) algorithm for decreasing metal objects in digital tomosynthesis (DT) for arthroplasty by using projection data. For metal artifact reduction (MAR), we implemented a DnCNN-MARHR algorithm based on a training network (mini-batch stochastic gradient descent algorithm with momentum) to estimate the residual reference (140 keV virtual monochromatic [VM]) and object (70 kV with metal artifacts) images. For this, we used projection data and subtracted the estimated residual images from the object images, involving hybrid and subjectively reconstructed image usage (back projection and maximum likelihood expectation maximization [MLEM]). The DnCNN-MARHR algorithm was compared with the dual-energy material decomposition reconstruction algorithm (DEMDRA), VM, MLEM, established and commonly used filtered back projection (FBP), and a simultaneous algebraic reconstruction technique-total variation (SART-TV) with MAR processing. MAR was compared using artifact index (AI) and texture analysis. Artifact spread functions (ASFs) for images that were out-of-plane and in-focus were evaluated using a prosthesis phantom. The overall performance of the DnCNN-MARHR algorithm was adequate with regard to the ASF, and the derived images showed better results, without being influenced by the metal type (AI was almost equal to the best value for the DEMDRA). In the ASF analysis, the DnCNN-MARHR algorithm generated better MAR compared with that obtained employing usual algorithms for reconstruction using MAR processing. In addition, comparison of the difference (mean square error) between DnCNN-MARHR and the conventional algorithm resulted in the smallest VM. The DnCNN-MARHR algorithm showed the best performance with regard to image homogeneity in the texture analysis. The proposed algorithm is particularly useful for reducing artifacts in the longitudinal direction, and it is not affected by tissue misclassification. [ABSTRACT FROM AUTHOR]

Background: Hydronephrosis is a common finding in patients with bladder cancer. The aim of the study was to appraise the prognostic value of preoperative hydronephrosis in bladder cancer patients undergoing radical cystectomy. Methods: We conducted a literature search using PubMed and Embase databases in Aug 2018. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effects models. The primary endpoint was overall survival (OS). Secondary endpoints were cancer-specific survival (CSS) and recurrence-free survival (RFS). Results: Overall, 13 studies published between 2008 and 2018 including 4,820 patients were selected for the meta-analysis. The age of bladder cancer patients ranged from 27 to 90.4 years, and the overall proportion of males was 72.5%. Preoperative hydronephrosis was reported in 27.4% of patients. The pooled HR was statistically significant for OS (HR, 1.36; 95% CI [1.20–1.55]) and CSS (HR, 1.64; 95% CI [1.33–2.02]), with no heterogeneity among the enrolled studies. Patients with bilateral hydronephrosis showed a poorer CSS compared to those with no hydronephrosis (HR 5.43, 95% CI [3.14–9.40]). However, there was no difference in CSS between no hydronephrosis and unilateral hydronephrosis groups (HR 1.35, 95% CI [0.84–2.14]). Despite a tendency towards poorer RFS (HR, 1.27; 95% CI [0.96–1.96]), the results demonstrated no significant association between presence of preoperative hydronephrosis and RFS after radical cystectomy. Conclusion: This meta-analysis indicates that preoperative hydronephrosis is significantly associated with poorer OS and CSS after radical cystectomy for patients with bladder cancer. Preoperative hydronephrosis has a stronger effect on CSS in patients with bilateral hydronephrosis. The presence of preoperative hydronephrosis not only predicts prognosis, but may also help to identify patients who benefit the most from neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: The frequency of postoperative complications is used as an indicator of surgical quality; however, comparison of outcomes is hampered by a lack of agreement on the definition of complications and their severity. A standard grading system for surgical complications is necessary to improve the quality of clinical research and reporting in head and neck reconstruction. Methods: The aim of this study was to compare postoperative morbidity after microvascular head and neck reconstruction between patients with versus without a history of prior radiation therapy (RT) by using the Clavien–Dindo classification. A group of 274 patients was divided into two cohorts based on the history of prior RT: the RT group included 79 patients and the non-RT group included 195 patients. Postoperative (30-day) complications were compared between the groups with a nonstandardized evaluation system and the Clavien–Dindo classification. Results: The grades of complications according to the Clavien–Dindo classification were significantly higher in the RT group than in the non-RT group. The frequency of postoperative complications did not differ significantly between the groups according to the nonstandardized evaluation system. Conclusions: The Clavien–Dindo classification could serve as a useful, highly objective tool for grading operative morbidity after microvascular head and neck reconstruction when comparing similar defects and methods of reconstruction. Widespread use of the Clavien–Dindo classification system would allow adequate comparisons of surgical outcomes among different surgeons, centers, and therapies. [ABSTRACT FROM AUTHOR]

Incidentally discovered solitary pulmonary nodules (SPN) caused by nontuberculous mycobacteria (NTM) is uncommon, and its optimal treatment strategy remains uncertain. This cohort study determined the clinical characteristics and outcome of asymptomatic patients with NTM-SPN after surgical resection. Resected SPNs with culture-positive for NTM in six hospitals in Taiwan during January, 2010 to January, 2017 were identified. Asymptomatic patients without a history of NTM-pulmonary disease (PD) or same NTM species isolated from the respiratory samples were selected. All were followed until May 1, 2019. A total of 43 patients with NTM-SPN were enrolled. Mycobacterium avium complex (60%) and M. kansasii (19%) were the most common species. The mean age was 61.7 ± 13.4. Of them, 60% were female and 4% had history of pulmonary tuberculosis. The NTM-SPN was removed by wedge resection in 38 (88%), lobectomy in 3 (7%) and segmentectomy in 2 (5%). Caseating granuloma was the most common histologic feature (58%), while chronic inflammation accounts for 23%. Mean duration of the follow-up was 5.2 ± 2.8 years (median: 4.2 years [2.5–7.0]), there were no mycobacteriology recurrence or NTM-PD development. In conclusion, surgical resection is likely to curative for incidentally discovered NTM-SPN in asymptomatic patients without culture evidence of the same NTM species from respiratory specimens, and routine mycobacterium culture for resected SPN might be necessary for differentiating pulmonary tuberculosis and NTM because further treatment differs. [ABSTRACT FROM AUTHOR]

Presence of preoperative sarcopenia is a risk factor for postoperative complications. However, there are few reports on the presence of sarcopenia and its characteristics following gastrectomy. Sarcopenia is closely related to quality of life in elderly people. To date, the main purpose of follow-up after gastrectomy is surveillance for early detection of recurrence and secondary cancer. However, henceforth, quality of life in elderly gastric cancer patients after gastrectomy must also be evaluated. The present study aimed to investigate sarcopenia during a 1-year postoperative course in elderly gastric cancer patients and examine their characteristics. The subjects were 50 patients aged ≥70 years who underwent laparoscopy-assisted distal gastrectomy for gastric cancer and who experienced no recurrence 1 year postoperatively. Height, weight, serum albumin levels, food intake amount, grip strength, gait speed, visceral fat area, and appendicular skeletal muscle mass index were measured preoperatively and 6 months and 1 year postoperatively. Sarcopenia, obesity, and visceral obesity were diagnosed. Compared with preoperatively, indicators other than height decreased 6 months postoperatively. Compared with 6 months postoperatively, body weight, amount of food intake, and visceral fat area increased by 1 year postoperatively, unlike appendicular skeletal muscle mass index. The frequency of sarcopenia increased 6 months postoperatively compared with preoperatively; this frequency remained almost unchanged 1 year postoperatively compared with 6 months postoperatively. Further, the frequency of visceral obesity increased 1 year postoperatively compared with 6 months postoperatively. Weight increased after > 6 months postoperatively; however, most of the weight increase was in terms of fat and not muscle. We emphasize the importance of considering postoperative sarcopenia and visceral obesity. In particular, sarcopenia and visceral obesity should be carefully monitored after increases in body mass index and food consumption. [ABSTRACT FROM AUTHOR]

Purpose: Data for elucidating post-kidney transplantation (KT) acute pancreatitis (AP) risk are limited and no large-scale cohort study has investigated the impact of AP after KT. Method: Data from Taiwan National Health Insurance (NHI) Research Database (NHIRD) were calculated through the method of propensity score matching to compare the pancreatitis risk in patients with and without KT. Results: The overall pancreatitis incidence rates were 1.71 and 0.61 per 1,000 person-years in the KT and non-KT groups, respectively and corresponding adjusted HR (aHR [95% CI]) for pancreatitis was 2.48 (1.51–4.09) in the KT group. In the multivariable model, AP risk was higher in transplant patients with alcohol-related illnesses (aHR: 3.78, 95% CI: 1.32–10.8), gall stone disease (aHR: 3.53, 95% CI: 1.48–8.44), or past history of pancreatitis (aHR: 10.3, 95% CI: 5.08–20.8). Of note, recurrent AP risk was significantly higher in the KT group (aHR: 8.19, 95% CI: 2.89–23.2). Patients with post-KT AP demonstrated shorter patient and allograft survival than did those without (both P < 0.001, respectively). Conclusion: In conclusion, KT recipients are very likely to be associated with AP. Moreover, their inferior outcomes are strongly associated with post-KT AP. [ABSTRACT FROM AUTHOR]

Background: The narrative surrounding the management of potentially resectable pancreatic cancer is complex. Surgical resection is the only potentially curative treatment. However resection rates are low, the risk of operative morbidity and mortality are high, and survival outcomes remain poor. The aim of this study was to create a prognostic Bayesian network that pre-operatively makes personalized predictions of post-resection survival time of 12months or less and also performs post-operative prognostic updating. Methods: A Bayesian network was created by synthesizing data from PubMed post-resection survival analysis studies through a two-stage weighting process. Input variables included: inflammatory markers, tumour factors, tumour markers, patient factors and, if applicable, response to neoadjuvant treatment for pre-operative predictions. Prognostic updating was performed by inclusion of post-operative input variables including: pathology results and adjuvant therapy. Results: 77 studies (n = 31,214) were used to create the Bayesian network, which was validated against a prospectively maintained tertiary referral centre database (n = 387). For pre-operative predictions an Area Under the Curve (AUC) of 0.7 (P value: 0.001; 95% CI 0.589–0.801) was achieved accepting up to 4 missing data-points in the dataset. For prognostic updating an AUC 0.8 (P value: 0.000; 95% CI:0.710–0.870) was achieved when validated against a dataset with up to 6 missing pre-operative, and 0 missing post-operative data-points. This dropped to AUC: 0.7 (P value: 0.000; 95% CI:0.667–0.818) when the post-operative validation dataset had up to 2 missing data-points. Conclusion: This Bayesian network is currently unique in the way it utilizes PubMed and patient level data to translate the existing empirical evidence surrounding potentially resectable pancreatic cancer to make personalized prognostic predictions. We believe such a tool is vital in facilitating better shared decision-making in clinical practice and could be further developed to offer a vehicle for delivering personalized precision medicine in the future. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of residual stenosis after carotid artery stenting (CAS) on periprocedural and long-term outcomes. Methods: Patients treated with CAS for symptomatic or asymptomatic carotid arterial stenosis were consecutively enrolled. Residual stenosis was estimated from post-procedure angiography findings. The effects of residual stenosis on 30-day periprocedural outcome and times to restenosis and clinical outcome were analyzed using logistic regression models and Wei-Lin-Weissfeld models, respectively. Results: A total of 412 patients (age, 64.7 ± 17.0 years; male, 82.0%) were enrolled. The median baseline stenosis was 80% (interquartile range [IQR], 70–90%), which improved to 10% (0–30%) for residual stenosis. Residual stenosis was significantly associated with periprocedural outcome (adjusted odds ratio, 0.983; 95% confidence interval [CI], 0.965–0.999, P = 0.01) after adjustment for baseline stenosis, age, hypertension, symptomaticity, and statin use. Over the 5-year observation period, residual stenosis did not increase the global hazard for restenosis and clinical outcome (adjusted hazard ratio, 1.011; 95% CI, 0.997–1.025. In the event-specific model, residual stenosis increased the hazard for restenosis (adjusted hazard ratio, 1.041; 1.012–1.072) but not for clinical outcome (adjusted hazard ratio, 1.011; 0.997–1.025). Conclusions: Residual stenosis after carotid artery stenting may be useful to predict periprocedural outcome and restenosis. [ABSTRACT FROM AUTHOR]