Search

Early mortality remains a challenging therapeutic facet of the initial induction phase of intensive chemotherapy in patients with acute myeloid leukemia (AML). The impact of standard molecular evaluation and risk category of the European LeukemiaNet (ELN) 2017 classification model on early mortality has not been rigorously evaluated thus far. We reviewed the medical records of 320 consecutive adult patients with newly diagnosed AML treated with intensive induction chemotherapy in our center from 2007 to 2021. The median age was 56 years; 33 patients (10%) died during induction. Patient age, white blood cell count, hemoglobin level, platelet level, creatinine, uric acid, lactate dehydrogenase serum levels, and FLT3-ITD and CEBPA mutational status did not significantly impact early mortality. NPM1

Favorable pathologic response(FPR) is a significant predictor for improved survival following Neoadjuvant therapy(NAT) in esophageal and gastroesophageal cancer(GEJ). Preoperative prediction of FPR could modify treatment plans. No reliable method for predicting FPR exists. We sought to identify preoperative predicting factors for FPR.Retrospective analysis of patients with esophageal and GEJ cancer who underwent esophagectomy following (NAT). Univariate and multivariate analysis was used to identify preoperative predicting factors for FPR. A comparison of Tumor Regression Grade(TRG) was used to assess treatment response on overall survival(OS).Out of 121 patients, 82(67.8%) had neoadjuvant chemoradiation. FPR was observed in 60(49.6%). Female sex, Radiation therapy(RT), squamous cell carcinoma(SCC), lack of signet ring feature, and FDG avidity posttreatment were associated with FPR on univariate analysis. RT and SCC were associated with FPR (OR=3.9 and 4.0, respectively) on multivariate analysis. OS was lower among patients who did not achieve FPR to NAT(P=0.027).FPR is a predictor of improved OS. SCC and radiation therapy-based protocol were identified as major prediction factors of FPR in patients with esophageal and GEJ cancers.

To investigate the distribution of parturients at Hospital Municipal da Vila Santa Catarina Dr. Gilson de Cássia Marques de Carvalho according to the Robson classification, identify the cesarean rate in each Robson Group, and understand which group contributes more to the prevalence of Cesarean sections.This is a retrospective observational cross-sectional study conducted through the analysis of medical records of parturients admitted to Hospital Municipal da Vila Santa Catarina Dr. Gilson de Cássia Marques de Carvalho from October 2016 to August 2019.A total of 9,794 births were recorded, and 31% were by Cesarean section. The most prevalent Robson Groups were Group 3 (25.7%-2,519), 1 (22.8%-2,234), and 5 (20.5%-2,006). The relative contribution of Cesarean sections was greatest in Groups 5 (39%), 2 (18%), and 1 (12.5%).This study demonstrated the Robson classification is useful to lead to a more critical view, identifying the groups that deserve more attention, since they are the major contributors to cesarean rates; hence, the management protocols could be modified aim to reduce cesarean rates.

Introduction: Metacognition is defined as the process of regulating behavior and having self-perception of own performance. An application of video modeling (VM) was used as a technological solution for assessing self-perception in daily situations among typical adolescents, compared to parental reports and to an objective performance-based assessment.Method: One hundred and three adolescents (30 boys, 73 girls, mean age =15.1, SD = 1.9), viewed five clusters of videotaped scenarios of teen actors performing daily activities entailing strategy use. Half of the scenarios were classified as "Type A" indicating a more organized approach to accomplishing a task, the other half were "Type B" scenarios indicated a less organized approach to accomplishing the same tasks. Participants were asked to choose the scenarios that best represent their own daily performance using the VM application. The participants then completed the WCPA, an executive function (EF) performance-based assessment. Their parents completed the BRIEF as an indication of EF behaviors in the home environment.Results: 46% of the adolescents associated their performance with a less organized approach yet parental reports indicated adaptive daily performance and their ability to complete the WCPA was as correct as it was for the 56% of participants who associated their performance with a more organized approach.Conclusions: Unexpectedly, the participants who associated their ability as less organized presented successful behaviors in the home environment and successfully performed the WCPA. Therapists should be aware that clients may achieve success in daily tasks even though they may cope with cognitive challenges in unexpected ways.Implication for rehabilitationTherapists may expect adolescent clients to approach tasks in a variety of ways, using different strategies for coping with everyday cognitive challenge.Therapists need to acknowledge that there is no ideal strategy that provides a solution for all individuals.Mediating a guided discovery of strategies through use of VM technology may customize intervention for each client's needs, assuring a client-centered approach and may encourage a collaboration of therapists and clients in search for the strategies that work best for them.

The accumulation of circulating low-density neutrophils (LDN) has been described in cancer patients and associated with tumor-supportive properties, as opposed to the high-density neutrophils (HDN). Here we aimed to evaluate the clinical significance of circulating LDN in lung cancer patients, and further assessed its diagnostic vs prognostic value. Using mass cytometry (CyTOF), we identified major subpopulations within the circulating LDN/HDN subsets and determined phenotypic modulations of these subsets along tumor progression. LDN were highly enriched in the low-density (LD) fraction of advanced lung cancer patients (median 7.0%; range 0.2%-80%, n = 64), but not in early stage patients (0.7%; 0.05%-6%; n = 35), healthy individuals (0.8%; 0%-3.5%; n = 15), or stable chronic obstructive pulmonary disease (COPD) patients (1.2%; 0.3%-7.4%, n = 13). Elevated LDN (>10%) remarkably related with poorer prognosis in late stage patients. We identified three main neutrophil subsets which proportions are markedly modified in cancer patients, with CD66b+ /CD10low /CXCR4+ /PDL1inter subset almost exclusively found in advanced lung cancer patients. We found substantial variability in subsets between patients, and demonstrated that HDN and LDN retain a degree of inherent spontaneous plasticity. Deep phenotypic characterization of cancer-related circulating neutrophils and their modulation along tumor progression is an important advancement in understanding the role of myeloid cells in lung cancer.

Treatment with tranexamic acid (TxA) significantly reduces maternal death due to postpartum hemorrhage. There is increasing interest in whether it can also be used as prophylaxis for postpartum hemorrhage, especially during cesarean sections (CS). This impact study is aimed to determine the effect of routine prophylactic tranexamic acid during CS on maternal hemorrhage and the rate of the associated side effects. This retrospective population-based cohort single-center impact study include 2000 women who delivered by CS divided into two groups with (n = 1000) and without (n = 1000) prophylactic administration of 1gram TxA prior to surgery. Primary outcomes were to determine the: (1) rate of women experiencing >10% or ≥2 g/dL hemoglobin drop from the preoperative concentration within 24 h after CS. (2) incidence of women having a hemoglobin drop of ≥2 g/dL. Women who did not receive TxA prophylactic had a higher rate of >10% hemoglobin decrease and a higher rate of ≥2 g/dL hemoglobin decrease Than those who received TxA prophylaxis (p < .0001, for both). Mean hospital stay (p = .002) and umbilical cord pH (p < .05) were higher among those who received TxA prophylaxis than in those who were not treated. The finding of our study suggest that prophylactic administration of TxA prior to CS improves maternal and neonatal outcomes.

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure 30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation

BACKGROUND: There is little information regarding diaphragmatic dysfunction (DD) following thoracic surgery. Ultrasound allows for non-invasive repeated assessments of diaphragmatic excursion (DE) and thickening fraction (DTF) at the bedside, reflecting DD. We aimed at determining the prevalence of DD and the time-course of DE and DTF following elective thoracic surgery. Secondary endpoints included the association between DD and postoperative complications. METHODS: We led a prospective, single center, observational study in consecutive patients undergoing thoracic surgery. DE and DTF were measured by two observers blinded to each other at 3 different time-points: prior to surgery (D-1), immediately after extubation (D0) and on postoperative day 3 (D3). The changes in excursion and thickening fraction of both hemi-diaphragms over time were compared according to the side (operated or non-operated) using a two-way ANOVA. The association with postoperative complications was assessed using logistic regression.RESULTS: Fifty patients, 60% males, aged 60±15 years were included. Surgical procedures included lobectomy (n=30), wedge-resection (n=17) or pneumonectomy (n=3). DD was highly prevalent after thoracic surgery and was observed on the operated side (or both sides) in, at least, 68% of patients immediately after surgery (D0). Among those patients, 46% still had this DD on the operated side on D3. On the operated side, we observed a decrease in DE and DTF at D0 (-0.71±0.12mm, PPPPP=0.001), ICU-admission (P=0.04) according to univariate analysis and a prolonged length in hospital (OR:1.3, 95% CI [1.1-1.7], P=0.016) according to multivariate analysis.CONCLUSIONS: Diaphragmatic Dysfunction (DD) was very common after thoracic surgery, mainly concerned the operated side and was associated with an increase in the diaphragmatic excursion on the non-operated side. When this dysfunction failed to regress within 72 hours, it was associated with a significant increase in the length of hospital stay.

Our hospital used to perform cesarean delivery under general anesthesia rather than neuraxial anesthesia, mostly because of patient refusal of members of the conservative Bedouin society. According to recommendations implemented by the Israeli Obstetric Anesthesia Society, which were implemented due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, we increased the rate of neuraxial anesthesia among deliveries.To compare the rates of neuraxial anesthesia in our cesarean population before and during SARS-CoV-2 pandemic.We included consecutive women undergoing an elective cesarean delivery from two time periods: pre-SARS-CoV-2 pandemic (15 February 2019 to 14 April 2019) and during the SARS-CoV-2 pandemic (15 February 2020 to 15 April 2020). We collected demographic data, details about cesarean delivery, and anesthesia complications.We included 413 parturients undergoing consecutive elective cesarean delivery identified during the study periods: 205 before the SARS-CoV-2 pandemic and 208 during SARS-CoV-2 pandemic. We found a statistically significant difference in neuraxial anesthesia rates between the groups: before the pandemic (92/205, 44.8%) and during (165/208, 79.3%; P0.0001).We demonstrated that patient and provider education about neuraxial anesthesia can increase its utilization. The addition of a trained obstetric anesthesiologist to the team may have facilitated this transition.

Retroperitoneal sarcoma is a rare malignancy arising from mesenchymal cells.[1][1] Surgical resection with wide negative margins remains the cornerstone of treatment as it decreases the risk of recurrence.[2][2] The proximity to critical abdominal structures makes a total resection with nerve and

Gut lymphocytes and the microbiota establish a reciprocal relationship that impacts the host immune response. Class I–restricted T cell–associated molecule (CRTAM) is a cell adhesion molecule expressed by intraepithelial T cells and is required for their retention in the gut. In this study, we show that CRTAM expression affects gut microbiota composition under homeostatic conditions. Moreover, Crtam−/− mice infected with the intestinal pathogen Salmonella exhibit reduced Th17 responses, lower levels of inflammation, and reduced Salmonella burden, which is accompanied by expansion of other microbial taxa. Thus, CRTAM enhances susceptibility to Salmonella, likely by promoting the inflammatory response that promotes the pathogen’s growth. We also found that the gut microbiota from wild-type mice, but not from Crtam−/− mice, induces CRTAM expression and Th17 responses in ex–germ-free mice during Salmonella infection. Our study demonstrates a reciprocal relationship between CRTAM expression and the gut microbiota, which ultimately impacts the host response to enteric pathogens.

Background Sentinel lymph node biopsy (SLNB) is routinely performed during surgery for malignant melanoma, using double mapping. Still, in some cases, a sentinel lymph node identified pre-operatively by lymphoscintigraphy is not identified during surgery. We hypothesized that disease specific survival would not be significantly impacted by intra-operative lymph node mapping (IOLM) failure. Methods The patient population study included 1300 malignant melanomas operated on by a single surgical oncologist (H.G.) after sentinel lymph node scintigraphy. Patients were included in the analysis if intra-operative lymph node (IOLM) mapping failed. Results Among 1300 patients who underwent surgery for malignant melanoma during the study period and after median follow up of >10 years, 33/36 lymphatic drainage basins with failed sentinel node identification were free of disease. Disease specific survival for the entire group of 33 patients with IOLM failure was 91.0%, which is comparable to previously published disease specific survival for all melanoma patients. Conclusion We conclude that failure to identify a pre-operatively marked sentinel lymph node by an experienced melanoma surgeon has, generally, no impact on disease specific survival, as demonstrated in this review of a series of surgical melanoma patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is a global health threat with the potential to cause severe disease manifestations in the lungs. Although COVID-19 has been extensively characterized clinically, the factors distinguishing SARS-CoV-2 from other respiratory viruses are unknown. Here, we compared the clinical, histopathological, and immunological characteristics of patients with COVID-19 and pandemic influenza A(H1N1). We observed a higher frequency of respiratory symptoms, increased tissue injury markers, and a histological pattern of alveolar pneumonia in pandemic influenza A(H1N1) patients. Conversely, dry cough, gastrointestinal symptoms and interstitial lung pathology were observed in COVID-19 cases. Pandemic influenza A(H1N1) was characterized by higher levels of IL-1RA, TNF-α, CCL3, G-CSF, APRIL, sTNF-R1, sTNF-R2, sCD30, and sCD163. Meanwhile, COVID-19 displayed an immune profile distinguished by increased Th1 (IL-12, IFN-γ) and Th2 (IL-4, IL-5, IL-10, IL-13) cytokine levels, along with IL-1β, IL-6, CCL11, VEGF, TWEAK, TSLP, MMP-1, and MMP-3. Our data suggest that SARS-CoV-2 induces a dysbalanced polyfunctional inflammatory response that is different from the immune response against pandemic influenza A(H1N1). Furthermore, we demonstrated the diagnostic potential of some clinical and immune factors to differentiate both diseases. These findings might be relevant for the ongoing and future influenza seasons in the Northern Hemisphere, which are historically unique due to their convergence with the COVID-19 pandemic.

Breast cancer subtypes have not shown significant response to current immunomodulatory therapies. Although most subtypes are treatable, triple negative breast cancer (TNBC), an aggressive highly metastatic cancer, comprising 10–20% of breast cancers, remains an unmet medical need. New strategies are needed in order to overcome flaws in the responsiveness to current TNBC therapies. Our aims were: first, to determine the efficacy of a novel immunomodulatory peptide, C24D, on TNBC and second, to elucidate the molecular mechanism by which C24D induces immune-modulating tumor killing. Using mass spectrometry analysis, we identified CD45 as the C24D binding receptor. In vitro and in vivo TNBC models were used to assess the efficacy of C24D in reversing TNBC-induced immunosuppression and in triggering immune-modulated tumor cell killing. The CD45 signal transduction pathway was evaluated by western blot and FACS analyses. We revealed that addition of PBMCs from healthy female donors to TNBC cells results in a cascade of suppressive CD45 intracellular signals. On binding to CD45’s extra-cellular domain on TNBC-suppressed leukocytes, the C24D peptide re-activates the Src family of tyrosine kinases, resulting in specific tumor immune response. In vitro, immune reactivation by C24D results in an increase of CD69+ T and CD69+ NK cells, triggering specific killing of TNBC cells. In vivo, C24D induced CD8+ and activated CD56+ tumor infiltrated cells, resulting in tumor apoptosis. Our results should renew interest in molecules targeting CD45, such as the C24D peptide, as a novel strategy for TNBC immunotherapy.

The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

A major mechanism through which neutrophils have been suggested to modulate tumor progression involves the interaction and subsequent modulation of other infiltrating immune cells. B cells have been found to infiltrate various cancer types and play a role in tumor immunity, offering new immunotherapy opportunities. Nevertheless, the specific impact of tumor-associated neutrophils (TAN) on B cells has largely been overlooked. In the current study, we aimed to characterize the role of TANs in the recruitment and modulation of B cells in the tumor microenvironment (TME). We showed that TANs actively participate in the recruitment of B cells to the TME and identified TNFα as the major cytokine mediating B-cell chemotaxis by TANs. The recruitment of CD45+B220+CD138− splenic B cells by TANs in vitro resulted in B-cell phenotypic modulation, with 68.6% ± 2.1% of the total migrated B cells displaying a CD45−B220+CD138+ phenotype, which is typical for plasma cells. This phenotype mirrored the large proportion (54.0% ± 6.1%) of CD45−B220+CD138+ intratumoral B cells (i.e., plasma cells) in Lewis lung carcinoma tumors. We next confirmed that the differentiation of CD45+B220+CD138− B cells to functionally active CD45−B220+CD138+ plasma cells required contact with TANs, was independent of T cells, and resulted in IgG production. We further identified membranal B-cell activating factor (BAFF) on TANs as a potential contact mechanism mediating B-cell differentiation, as blocking BAFF-receptor (BAFF-R) significantly reduced IgG production by 20%. Our study, therefore, demonstrates that TANs drive the recruitment and modulation of B cells into plasma cells in the TME, hence opening new avenues in the targeting of the immune system in cancer.

Purpose According to most guidelines, medical protocol for carotid stenting includes the administration of oral Aspirin and Clopidogrel at least four days before the procedure, with intraprocedural intravenous (IV) heparin. Some publications have also reported the safety of adding glycoprotein 2b/3a inhibitors to the protocol. In this retrospective study, we evaluate the safety of a new medication protocol that includes IV aspirin and intra-arterial Eptifibatide (glycoprotein 2b/3a inhibitor) during carotid stenting. All patients who underwent carotid stenting at Soroka University Medical Center between January 2015 and May 2020 were included (emergent cases were excluded). We divided patients into two groups—patients treated under the standard protocol, and patients treated under the new protocol. In the latter, patients received both the standard protocol regimen, as well as 150 mg IV aspirin immediately before stenting, and a slow intra-arterial injection of 2–3 mg Eptifibatide (glycoprotein 2b/3a antagonist) immediately after stenting. Forty-four patients were treated according to the standard protocol (group 1), and 41 patients were treated according to the new protocol (group 2). In group 1, six patients had complications, while in group 2, no complications of any kind were noted (p = 0.027). The safety and possible efficacy of this novel protocol was preliminarily demonstrated in the present study. Future studies are needed to prove the safety and efficacy of a specific drug regimen that will further reduce the complication rates of carotid stenting.

Background Symptomatic carotid stenosis is responsible for 10% of all strokes. Currently, CT angiography (CTA) is the main diagnostic tool for carotid stenosis. It is frequently the only diagnostic test preceding recommendations for carotid angioplasty and stenting (CAS) or carotid endarterectomy (CEA). However, the specificity of CTA, especially in patients with 50–70% stenosis, was previously reported to be relatively low. Most studies testing the diagnostic accuracy of CTA were published more than a decade ago. Therefore, we aimed to test the diagnostic accuracy of CTA, performed with current available technology, compared with digital subtraction angiography (DSA) in patients with carotid stenosis. This study aims to characterize patients who were candidates for CAS/CEA based on CTA, but may not require it based on DSA. Methods Consecutive candidates for carotid interventions (CAS or CEA) following CTA were identified from prospectively maintained stroke center registries at two large academic centers. As part of our institutional practice all patients had a routine pre-procedural diagnostic DSA. In each patient, degree of carotid stenosis was compared between CTA and DSA. Patients with concordant degree of stenosis on DSA and CTA (true positive group) were compared to patients with a discordant degree of stenosis with less than 50% on DSA (false positive group). Results Out of 90 patients with significant stenosis on CTA, only 70 (78%) were found to have a significant stenosis on DSA. Severe plaque calcification was significantly more common in the false-positive group. In those patients whose CTA reported stenosis of ≥90%, we found a strong agreement between CTA and DSA (positive predictive value [PPV] – 0.9) for a significant stenosis (≥50%). Conversely, the correlation between CTA and DSA in patients with CTA reported 50–70% stenosis was poor (PPV – 0.29) (p Conclusions Our results suggest that despite ongoing radiological progress, the specificity of CTA in accurately assessing carotid stenosis remains relatively low in patients with both moderate stenosis and heavily calcified plaques. Consequently, patients could possibly be referred for unnecessary CEA surgery and may become exposed to associated potential complications.

Background Ischemic stroke is one of the leading causes of mortality and morbidity. The currently available non-invasive therapeutic options are not sufficiently efficacious. Post-ischemic brain is characterized by a prominent inflammatory response. Little is known about the involvement of cyclooxygenase (COX)-1 in the pathophysiology of ischemic stroke. Objective This study was undertaken to examine the effects of a highly selective COX-1 inhibitor – mofezolac – on clinical outcomes and brain inflammatory markers in post-stroke rats. Methods Stroke was induced by subjecting rats to permanent middle cerebral artery occlusion (MCAO). Control rats underwent a sham surgery. Rats were treated with mofezolac (50 mg/kg, intraperitoneally [ip]) once daily for 14 days. Control animals were treated with vehicle. Body temperature (BT), neurological score (NS) and cumulative mortality were monitored at different time points. At the end of the experiment, rats were euthanized and three brain regions (hypothalamus, hippocampus and frontal cortex) were extracted. Levels of interleukin (IL)-6, prostaglandin (PG)E2 and tumor necrosis factor (TNF)-α in these brain regions were determined by ELISA kits. Results BT, NS and cumulative mortality were all significantly higher in post-MCAO rats than in sham-operated rats, irrespective of the treatment given. BT, NS and mortality rate did not differ significantly between mofezolac-treated and vehicle-treated sham-operated animals. BT was significantly lower in mofezolac-treated as compared to vehicle-treated post-MCAO rats. Mofezolac did not significantly alter NS in post-MCAO rats at any time-point. Cumulative 14-day mortality was non-significantly higher in mofezolac-treated as compared to vehicle-treated post-MCAO rats (48 % vs. 21 %, respectively; P = 0.184). Mostly, IL-6 and TNF-α levels did not differ between post-MCAO and sham-operated rats and were not affected by mofezolac treatment. In contrast, mofezolac significantly decreased PGE2 levels in post-MCAO rats’ brains. Conclusion Overall, these results suggest that chronic treatment with the selective COX-1 inhibitor mofezolac did not reduce morbidity or mortality in post-stroke rats.

People with Parkinson's disease have been shown to have difficulty switching between movement plans. In the great majority of studies, the need to switch between tasks was made explicitly. Here, we tested whether people with Parkinson's disease, taking their normal medication, have difficulty switching between implicitly specified tasks. We further examined whether this switch is performed predictively or reactively. Twenty five people with Parkinson's disease continuously increased or decreased the frequency of their arm movements, inducing an abrupt-but unaware-switch between rhythmic movements (at high frequencies) and discrete movements (at low frequencies). We tested whether that precipitous change was performed reactively or predictively. We found that 56% of participants predictively switched between the two movement types. The ability of people with Parkinson's disease, taking their regular medication, to predictively control their movements on implicit tasks is thus preserved.

Background: The symptoms of patients with Parkinson’s disease (PD) have been shown to improve when they perform fast-paced rhythmic cycling movements with their lower limbs. Objective: Our goal in this pilot experiment was to test the feasibility and the benefits of a short exercise program involving fast-paced rhythmic movements of the upper limb for patients with PD. Methods: We used an experimental procedure that elicits large, fast-paced movements by the participants without the direct instructions to do so by the experimenter. Ten participants with PD (71.0±6.5 years old) performed a 50-min fast-paced rhythmic exercise of the upper limb after withdrawal from PD medication for at least 12 hours. Results: Participants improved their kinematic performance, in terms of accuracy and combined speed and amplitude (p

Objectives To assess the economic impact of introducing the soluble FMS-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in two Brazilian hospitals. Methods An economic model estimating the incremental value of the information from a Brazilian public and private healthcare payer perspective generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. A cohort of 1000 pregnant women between 24 weeks and 36 + 6 weeks of gestation were managed in either a ‘test’ scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a ‘no-test’ scenario. Information on the costs associated with diagnosis, prediction and management were derived from the cost database of Hospital M'Boi Mirim (public) and Hospital Einstein (private). The probabilities used in the decision tree were derived from PROGNOSIS. The main outcome measure from the model was the cost per patient per episode of care (from first suspicion of pre-eclampsia to birth). Results Introduction of the sFlt-1/PlGF ratio test resulted in cost savings in both settings (M’Boi Mirim: R$185.06 and Einstein: R$635.84 per patient) compared with a ‘no-test’ scenario. Savings are generated primarily through an improvement in diagnostic accuracy and a reduction in unnecessary hospitalization. Conclusions The sFlt-1/PlGF ratio test has the potential to improve clinical decision-making and allocation of scarce resources by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia, and ensuring that women at higher risk are identified and managed appropriately.

Studies have characterised relationships between cognitive status and a variety of clinical epilepsy factors. The aim of this study was to describe a new approach for assessing executive functions in everyday life and its unique expression in adolescents with Genetic Generalised Epilepsies (GGEs) compared with typical peers. Twenty adolescents with a diagnosis of GGEs and 20 typical healthy peers, matched by age and gender, were studied. Assessment of everyday executive function was carried out using: (1) the Weekly Calendar Planning Activity (WCPA), a direct performance based and outcome measure of strategy use and cognitive performance; and (2) Behavior Rating Inventory of Executive Function (BRIEF) parental report. Adolescents with GGEs demonstrated significantly less accuracy, less efficiency and fewer strategies used, as measured by the WCPA. Parents of adolescents with GGEs rated their child's daily performance as less efficient compared with typical peers. Better ratings of executive function (low BRIEF score) were associated with greater WCPA accuracy in the entered appointments. The WCPA provides a useful evaluation of cognitive performance for adolescents with GGEs and a functionally relevant information on task efficiency, self-monitoring and effective strategy use. Direct observation of performance supplements parental ratings and has strong potential to guide intervention and measure outcomes.

Social work education plays a critical role in preparing social workers to lead efforts that improve health. Because of the dynamic health care landscape, schools of social work must educate students to facilitate health care system improvements, enhance population health, and reduce medical costs. We reviewed the existing contributions of social work education and provided recommendations for improving the education of social workers in 6 key areas: aging, behavioral health, community health, global health, health reform, and health policy. We argue for systemic improvement in the curriculum at every level of education, including substantive increases in content in health, health care, health care ethics, and evaluating practice outcomes in health settings. Schools of social work can further increase the impact of the profession by enhancing the curricular focus on broad content areas such as prevention, health equity, population and community health, and health advocacy.

OBJECTIVE: To evaluate the effects of early treatment with CPAP on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants. STUDY DESIGN: EPT infants (24–0/7 to 27–6/7 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks’ postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks’ PMA and follow-up outcomes at 18–22 months’ corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed. RESULTS: 810 of 1316 infants enrolled in SUPPORT (414 in intervention group, 396 in control group) had growth data analyzed. Median gestational age was 26 weeks and mean birthweight was 839 grams. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between groups. In a regression model, growth rates between birth and 36 weeks’ PMA as well as growth rates during multiple intervals from birth to day 7, day 7 to14, day 14 to 21, day 21 to 28, day 28 to 32 weeks’ PMA, and 32 weeks’ PMA to 36 weeks’ PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of Bayley III cognitive score

Objective We aimed to determine whether fecal microbiota transplant (FMT) is safe and possibly efficacious in treating constipation, motor, and non-motor symptoms in Parkinson's disease (PD) patients. Methods Patients with PD, constipation and an indication for screening colonoscopy were treated with FMT. The study was conducted from December 2017 to November 2019, and clinical outcomes assessing motor, non-motor and constipation symptoms were compared at baseline (week 0) and at 2, 4, 8, 12, 16, 20, and 24 weeks after the FMT. Results Six patients (3 men, age range 47–73, median age 52) were treated with FMT. Four weeks following the FMT, motor, non-motor and constipation scores were improved in 5 of 6 patients. At week 24, compared to before the FMT, the changes in motor scores ranged from − 13–7 points, in non-motor scores from − 2 to − 45 points, and in constipation scores from − 12–1 point. One patient had a serious adverse event requiring admission for observation only, and no adverse events were observed in all other patients. Conclusions In this preliminary uncontrolled case series of 6 PD patients, a treatment with donor FMT infused via colonoscopy, was safe and resulted in improvement of PD motor and non-motor symptoms, including constipation, at 6 months. Further research is needed to assess longer-term maintenance of efficacy and safety, including in large scale randomized controlled trials. Trial registration ClinicalTrials.gov – NCT03876327

Background:Inadvertent hyperthermia during anaesthesia is a rare but life-threatening complication. We have encountered several cases of severe hyperthermia in paediatric patients undergoing anaesthesia for cochlear implantation.Methods:This study aimed to describe the clinical characteristics of children who developed hyperthermia while undergoing cochlear implantation, and to explore possible mechanisms and predisposing factors. The anaesthetic charts of all patients aged under 18 years who underwent cochlear implantation, or mastoid or ophthalmic surgery, between 1 January 2006 and 31 December 2009, at Soroka Medical Center in Beer Sheva, Israel, were reviewed. Patients undergoing mastoid and ophthalmic surgical procedures were used as controls.Results:A larger percentage of patients who underwent cochlear implant surgery (10 per cent) developed hyperthermia compared to controls (0.7 per cent, p < 0.05). In five of the seven cases, hyperthermia appeared in combination with tachycardia and hypercapnia, adhering to the clinical triad of malignant hyperthermia.Conclusion:Patients undergoing cochlear implantation are susceptible to developing intra-operative hyperthermia. This article describes the hyperthermic events that occur during paediatric cochlear implantation, and attempts to identify potential triggers of hyperthermia.

Serious complications in obstetric anesthesia are a rare occurrence. High neuraxial block, respiratory arrest in labor and delivery, and an unrecognized spinal catheter are among the most frequently reported serious complications. A serious complication occurs in approximately 1:3000 obstetric patients. Neuraxial hematoma after obstetric epidural analgesia or anesthesia is extremely rare. We present a case of a puerperal spinal epidural hematoma following epidural labor analgesia. The patient presented with foot drop, which resolved after conservative treatment. We reviewed the epidemiology, clinical manifestations and treatment options for this rare complication.

Objective To analyze the pregestational body mass index and weight gain during pregnancy, and to associate data to perinatal outcomes of pregnant women from a Prenatal Care Program. Methods A retrospective study was carried out with 151 patients seen at the Healthy Gestation Program of Hospital Israelita Albert Einstein . Data were collected from a medical chart review of the patients seen between March 2015 and March 2016. Results The chance of developing gestational diabetes for obese patients in early gestation was estimated at 7.5-fold as compared to patients with low or normal body mass index. Conclusion There was a significant association between obesity in early pregnancy and the occurrence of gestational diabetes mellitus in this population.

Background To compare covert closed-circuit television (CCTV) monitoring to standard overt observation in assessing the hand hygiene (HH) conduct of health care workers (HCWs) caring for patients infected with multidrug-resistant organisms (MDROs). This was a cross-sectional study in a general intensive care unit of a 1,000-bed university hospital. Methods Forty-six general intensive care unit HCWs (staff physicians, registered nurses, and auxiliary workers) caring for contact isolation MDRO-infected patients. The study incorporated the following 3 phases: phase 1, establishment of interrater reliability between 2 simultaneous observers using the overt observation method; phase 2, establishment of interrater reliability between 2 simultaneous observers using the CCTV method; and phase 3, simultaneous monitoring of HH by both methods to evaluate the suitability of CCTV as an alternative to direct observation of the HH conduct of HCWs caring for MDRO-infected patients. Results Overall, 1,104 opportunities to perform HH were documented during 49 observation sessions. The compliance rate observed by the overt method (37.3%) was significantly higher than that observed when only the covert method was used (26.5%). However, simultaneous overt-covert observations were found to have intraclass correlation coefficients of >0.85. Conclusions Covert CCTV observation of HCW HH compliance appears to provide a truer and more realistic picture than overt observation, probably because of its ability to neutralize the Hawthorne effect of overt observation. The high intraclass correlation coefficients between covert observation and overt observation supports this conclusion.

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores’ limited discriminative capacity.

Objective To evaluate the prevalence of group B Streptococci in pregnant women of a corporate health program, as well as the epidemiological correlations. Methods This retrospective study used medical records of patients who participated of the prenatal care program at a private hospital in the city of São Paulo (SP), Brazil, from 2015 to 2016. Those who abandoned the program or had incomplete data in their medical records were excluded. Quantitative variables were described by means, standard deviations, median, minimal and maximal values. Parity and socioeconomic status were described by absolute frequency and percentages. We used logistic regression models in the software (SPSS) to analyze correlations of variables according to vaginal-rectal culture, considering a 95%CI and p-values. Variables were age, number of pregnancies, weight gain in pregnancy and gestational age at delivery. Results A total of 347 medical records were included, and after applying the exclusion criteria, 287 medical records composed the final sample. Patients’ age ranged between 17 and 44 years. Mean age was 30.6 years, 67 patients had positive result for group B Streptococcus (prevalence of 23.3%; 95%CI: 18.7-28.5). Conclusion Considering the high prevalence of group B Streptococcus in our service, the antibiotic prophylaxis strategy based on rectovaginal culture screening approach seems to be cost-effective. RESUMO Objetivo Identificar a prevalência de estreptococo do grupo B entre gestantes que frequentaram um programa de saúde corporativa, bem como as correlações com a colonização positiva. Métodos Estudo retrospectivo dos prontuários do pré-natal de um hospital privado em São Paulo, no período de 2015 a 2016. Foram excluídas as mulheres que abandonaram o programa ou apresentavam dados incompletos nos prontuários. As variáveis quantitativas foram descritas por média, desvios padrão, mediana, valores mínimos e máximos. A paridade e a condição socioeconômica foram descritos por frequência absoluta e percentagens. Utilizamos modelos de regressão logística no programa (SPSS) para analisar as correlações de variáveis de acordo com a cultura retovaginal, considerando IC95% e valores de p. As variáveis foram idade, número de gestações, peso ganho na gestação e idade gestacional no parto. Resultados Foram incluídos 347 prontuários e, após a aplicação dos critérios de exclusão, 287 prontuários compuseram a amostra final. A idade dos pacientes variou entre 17 e 44 anos. A média de idade foi de 30,6 anos, e 67 pacientes tiveram resultado positivo para o estreptococo do grupo B (prevalência de 23,3%; IC95%: 18,7-28,5). Conclusão Considerando a alta prevalência de estreptococos do grupo B em nosso serviço, existem evidências de que a estratégia de antibiótico profilaxia baseada na cultura retovaginal é custo-efetiva.

Maternal-deprivation of rodent pups is a relevant model of extreme early-life stress that can be relevant to the understanding of long-term effects of war, migration, parental loss and displacement. Although even mild stress during infancy affects brain development and behavior, the current study focused on the effects of six hour daily maternal-separation, a model that reflects the severe distress often experienced in those circumstances. This study emphasizes the effect of maternal separation on social behavior in the context of a variety of factors that measure cognitive and emotional behavior which were subject to principle component analysis. Sprague-Dawley pups were separated from the dam for 6 h each day during the first 3-weeks of life and underwent a battery of behavioral tests at 3-months of age. We found that rodents exposed to postnatal maternal deprivation displayed submissive behavior in resident-intruder and dominant-submissive tests, as well as significantly more anxiety and anhedonia than control rats. The results of multivariate statistical analysis show that the dominant-submissive behavior correlates with depressive, anxiety and social behavior and can be predicted with an accuracy of 86.2%. The increased submissive behavior in male rats that had been subjected to severe postnatal stress suggests that exposure to stress during infancy and childhood could have long-term effects on social relationships. The mechanism of the long-term effects on depression, anxiety and submissive behavior requires further investigation.

The usage of decision support tools in emergency departments, based on predictive models, capable of estimating the probability of admission for patients in the emergency department may give nursing staff the possibility of allocating resources in advance. We present a methodology for developing and building one such system for a large specialized care hospital using a logistic regression and an artificial neural network model using nine routinely collected variables available right at the end of the triage process.A database of 255.668 triaged nonobstetric emergency department presentations from the Ramon y Cajal University Hospital of Madrid, from January 2011 to December 2012, was used to develop and test the models, with 66% of the data used for derivation and 34% for validation, with an ordered nonrandom partition. On the validation dataset areas under the receiver operating characteristic curve were 0.8568 (95% confidence interval, 0.8508-0.8583) for the logistic regression model and 0.8575 (95% confidence interval, 0.8540-0. 8610) for the artificial neural network model. χ Values for Hosmer-Lemeshow fixed "deciles of risk" were 65.32 for the logistic regression model and 17.28 for the artificial neural network model. A nomogram was generated upon the logistic regression model and an automated software decision support system with a Web interface was built based on the artificial neural network model.

Purpose: Acinetobacter baumannii is a multidrug resistant (MDR), gram-negative bacterium commonly implicated in ventilator-associated pneumonia (VAP) in critically ill patients. Patients in the intensive care unit (ICU) with VAP often subsequently develop A baumannii bacteremia, which may significantly worsen outcomes. Materials and Methods: In this study, we retrospectively reviewed the clinical and laboratory records of 129 ICU patients spanning 6 years with MDR A baumannii VAP; 46 (35%) of these patients had concomitant MDR A baumannii bacteremia. Results: The ICU mortality rate was higher in patients with VAP having A baumannii bacteremia compared to nonbacteremic patients (32.4% vs 9.6% respectively, P < .005). Age >65 years, an Acute Physiology and Chronic Health Evaluation II (APACHE-II) score higher than 20, a Sequential Organ Failure Assessment (SOFA) score higher than 7 on the day of bacteremia, and the presence of comorbid disease (chronic obstructive pulmonary disease [COPD] and chronic renal failure) were found to be independent risk factors for in-hospital mortality in this population. Multidrug resistant A baumannii was not an independent risk factor for mortality. Conclusion: Although the presence of comorbid diseases (COPD and chronic renal failure) and severity of disease (APACHE > 20 and SOFA >7) were found to be independent risk factors for ICU mortality, MDR A baumannii bacteremia was not an independent risk factor for mortality in our critically ill population.

Objective Depression guidelines discourage benzodiazepine monotherapy and limit use to short-term adjunctive therapy with antidepressants; however, patients with depression continue to receive benzodiazepine monotherapy. The prevalence and predictors of this prescribing pattern have not been described previously and are warranted to assist clinicians in identifying patients at highest risk of receiving benzodiazepine monotherapy. Methods A national, cross-sectional analysis of the National Ambulatory Medical Care Survey from 2012 to 2015 was performed for adults treated for depression. Depression was identified using a survey item specifically assessing the presence of depression. Office visits involving patients with bipolar disorder, schizoaffective disorder, or pregnancy were identified by ICD-9 code or specific survey item and were excluded. The primary endpoint was benzodiazepine monotherapy prescribing rate defined as initiation or continuation of a benzodiazepine in the absence of any antidepressant agent. A multivariate logistic regression model was created to identify variables associated with benzodiazepine monotherapy. Results In total, 9,426 unweighted visits were eligible for inclusion. Benzodiazepine monotherapy was identified in 9.3% of patients treated for depression (95% CI, 8.2%-10.6%). Predictors of benzodiazepine monotherapy included age of 45-64 years (OR = 1.39; 95% CI, 1.01-1.91), epilepsy-related office visit (OR = 5.34; 95% CI, 1.39-20.44), anxiety-related office visit (OR = 1.67; 95% CI, 1.23-2.27), underlying pulmonary disease (OR = 1.43; 95% CI, 1.09-1.87), and concomitant opiate prescribing (OR = 2.86; 95% CI, 2.01-4.06). Psychiatrists were less likely to prescribe benzodiazepine monotherapy than were other providers (OR = 0.42; 95% CI, 0.29-0.61). Conclusions Benzodiazepine monotherapy is utilized in nearly 1 in 10 patients treated for depression. Adults aged 45 to 65 years, patients prescribed opioids, patients seen by primary care providers, and those with underlying anxiety, epilepsy, or pulmonary disorders are at highest risk.

Background Mineralocorticoid receptor antagonists (MRAs) improve survival among patients with heart failure with reduced ejection fraction (HFrEF); however, studies have identified low utilization rates. No study has evaluated the prevalence and predictors of MRA prescribing in a nationally representative outpatient cohort. Study question What is the prevalence and predictors of MRA prescribing among outpatients with HFrEF in the United States? Study design A national cross-sectional secondary analysis of the National Ambulatory Medical Care Survey from 2007 to 2014 including all office visits for HFrEF in patients aged >55 years. Office visits involving patients with any history of chronic renal failure and hyperkalemia were excluded. Measures and outcomes The primary end point was the MRA prescribing rate. Multivariable logistic regression models were created to identify predictors of use. Results In total, 1259 visits were eligible for inclusion, representing more than 30 million visits when weighted. MRAs were initiated or continued in 11.1% of HFrEF visits (95% confidence interval [CI] 8.8-13.8). In the full model, predictors included diabetes mellitus (OR 2.27; 95% CI 1.12-4.61), Northeast region (OR 0.20; 95% CI 0.05-0.74), and ≥4 chronic conditions (OR 0.26; 95% CI 0.10-0.71). Among symptomatic patients, predictors included non-Hispanic black patients (OR 4.55; 95% CI 1.81-11.43), patients aged 65-74 years (OR 3.38; 95% CI 1.53-7.44), and office systolic blood pressure >130 mm Hg (OR 0.31; 95% CI 0.16-0.60). Physician specialty, visit year, patient sex, and payor type were not significant predictors of MRA utilization. Conclusions Although significant data support the use of MRA in HFrEF, utilization is lower than previously estimated.

Dynamic changes in urine output and neurological status are the recognized clinical signs of hemodynamically significant hemorrhage. In the present study, we analyzed the dynamic minute-to-minute changes in the UFR and also the changes in its minute-to-minute variability in a group of critically ill multiple trauma patients whose blood pressures were normal on admission to the ICU but who subsequently developed hypotension within the first few hours of their ICU admission. The study was retrospective and observational. Demographic and clinical data were extracted from the computerized register information systems initially; the clinical and laboratory data of 100 critically ill patients with multiple trauma who were admitted to the ICU during the study period were analyzed. Of this group, ten patients were eventually included in the study on the basis of the inclusion criteria. The minute-to-minute urine flow rate (UFR) and urine flow rate variability (UFRV) both decreased significantly during the periods of hypotension (p values 0.001 and 0.006, respectively). Notably, the decrease in UFRV preceded by at least 30 min a corresponding decline in the systolic and mean arterial blood pressures, which manifested as a flattening of UFRV amplitude which was observed prior to the occurrence of the lowest recorded systolic and mean arterial blood pressures. Statistical analysis by the Pearson method demonstrated a strong direct correlation between the decrease in UFRV and the decrease in the MAP (R = 0.9, p = 0.001), and SBP (R = 0.86, p = 0.001) and the decreasing urine output per hour (R = 0.88, p