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Retinopathy of prematurity (ROP), a preventable cause of childhood blindness, is a severe complication of preterm (PT) birth treatment.The purpose of this study is to analyse the risk factors (RF) associated with the development and progression of ROP. Particular focus is on the contribution of anaemia towards the development and progression of ROP.This study is a prospective observational study done in the Department of Paediatrics at Meenakshi Mission HospitalResearch Centre, Madurai, over 12 months from May 2013 to April 2014. The study included all consecutively admitted neonates born in and out of the hospital with gestational age (GA) less than or equal to 35 weeks or birth weight (BW) less than or equal to 2 kg and assessed for the gestational, perinatal, and postnatal RF. In addition, at the time of ROP screening, haemoglobin (Hb) and haematocrit (Hct) were checked. The statistical analysis was performed by Stata 11.1 (StataCorp LLC, College Station, TX).The incidence of ROP in our study (46.7%) is higher than previously reported in India. In our study, GA and weight of the neonate at birth have a significant association with ROP incidence. Anaemia in our study is significantly associated with ROP incidence but not as an independent RF. The outcome of various stages of ROP is statistically significant, showing early stages 1 and 2 have more chances of spontaneous regression, and stages 3 and 4 are more likely to need treatment. Two cases in our study with stage 4 ROP had no complications, and none had stage 5 disease.Anaemia should be avoided or corrected in PT newborns as it is a potential and avoidable RF for ROP development. The limitation of our study is the small sample size, and probably more extensive randomized trials will help make this association clear. We recommend ROP screening for PT babies with GA less than 35 weeks and BW less than 2 kg who have the RF amounting to screening and done as per protocol.

Patient morbidity and mortality decrease when injured patients meeting CDC Field Triage Criteria (FTC) are transported by emergency medical services (EMS) directly to designated trauma centers (TCs). This study aimed to identify potential disparities in the transport of critically injured patients to TCs by EMS.We identified all patients in the National EMS Information System (NEMSIS) database in the National Association of EMS State Officials East region from January 1, 2018, to December 31, 2019, with a final prehospital acuity of critical or emergent by EMS. The cohort was stratified into patients transported to TCs or non-TCs. Analyses consisted of descriptive epidemiology, comparisons, and multivariable logistic regression analysis to measure the association of demographic features, vital signs, and CDC FTC designation by EMS with transport to a TC.A total of 670,264 patients were identified as sustaining an injury, of which 94,250 (14%) were critically injured. Of those 94,250 critically injured, 56.0% (52,747) were transported to TCs. Among all critically injured women (n = 41,522), 50.4% were transported to TCs compared with 60.4% of critically injured men (n = 52,728, p0.001). In a multivariable logistic regression model, critically injured women were 19% less likely to be taken to a TC compared with critically injured men (OR 0.81, 95% CI 0.71-0.93, p = 0.003).Critically injured female patients are less likely to be transported to TCs when compared with their male counterparts. Performance improvement processes that assess EMS compliance with field triage guidelines should explicitly evaluate for sex-based disparities. Further studies are warranted.

To evaluate the incidence and clinical indications for which eyes were treated for retinopathy of prematurity (ROP) outside the guidelines set by International Classification of ROP (ICROP). Medical records of the patients treated at a single tertiary care ophthalmology hospital for ROP from January 2016 to December 2019 were retrospectively analysed to evaluate the indications for which they were treated. Out of 241 eyes, 33 eyes (13.7%) were treated outside the guidelines. The reasons for the treatment outside the guidelines were structural changes (n = 24, 72.7%), persistent stage 3 ROP that did not show any sign of regression for 6 weeks (n = 7, 21.2%) and active ROP with fellow eye being treated (n = 2, 6.1%). The recorded specific structural changes were tangential traction with temporal vessel straightening concerning for macular distortion and ectopia (n = 5, 15.2%), and stage 3 neovascularisation or ridge with anteroposterior traction with risk of progression to stage 4 disease (n = 19, 57.6%). Pre-plus disease was present in 11 eyes (33.3%).After the treatment, ROP stages regressed and retinal vessels grew either until the ora or at least into zone III in all the treated eyes. None of the eyes showed worsening of structural changes after treatment. The mean follow-up of the patients was 12.4 ± 11.7 months. Experts occasionally recommend treatment in eyes with disease milder than type 1 ROP. This study may help paediatric retinal practitioners in decision-making in borderline cases.

This study evaluated the safety of early anti-factor Xa assay–guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay–guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.

Urine neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL- 18) have shown promise for predicting renal graft recovery. However, urinary flow rate variations may cause variable biomarker dilution. Plasma NGAL and IL-18 may form a biomarker panel that may help predict delayed graft function and slow graft function (SGF) in renal transplant recipients within the first two postoperative days earlier than serum creatinine. There are only a few studies in the literature using plasma NGAL for predicting renal graft recovery. Hence, we planned this study. This observational single-center, prospective cohort study was conducted in renal transplant recipients above 18 years of age. In 22 consecutive renal transplant recipients, we collected ethylenediaminetetraacetic acid-plasma samples 1 h before surgery and subsequently at 6 h, 24 h, and 48 h after surgery for NGAL and IL-18 by sandwich enzyme-linked immuno-sorbent assay technique. Serum creatinine was measured as a part of routine transplant protocol. In renal transplant recipients, neither serum levels of NGAL and IL-18 nor their trends could reliably predict SGF. The only significant correlation existed between serum creatinine at day 2 and IL-18 at day 2 with P = 0.023. Serum NGAL did not correlate with serum creatinine in this setting of renal transplantation. Patients with immediate graft function had a greater percentage decrease of creatinine at day 1 and day 2 (P = 0.002 and 0.001) The percentage change in IL-18 at 24 h and 48 h after transplant from baseline could predict the occurrence of early graft loss (EGL) (P = 0.05, 0.04). The cutoffs were -4.12% at day 1 and +3.39% at day 2 with area under receiver operator characteristics of 0.82 and 0.83, respectively. The percentage change in IL-18 may be a useful marker of EGL in renal transplant recipients. Serum NGAL and creatinine were not able to predict EGL.

Simple Summary Bone metastasis is a leading cause of breast cancer-related deaths. The interaction between metastatic cancer cells and bone-resident cells promotes tumor growth and bone loss. Metastatic tumors within the bone can contribute to complications including pathological fracture, hypercalcemia, spinal cord compression, and pain. The underlying molecular mechanisms that regulate these interactions in the bone microenvironment are not completely understood. Multiple cell signaling pathways, transcription factors, miRNAs, and secretory factors have been shown to promote bone metastasis. Here, we review the mechanisms by which tumor-derived and tumor-microenvironment-derived factors contribute to bone metastasis. We discuss recent findings highlighting the role of cell signaling and the autophagy pathway in bone metastasis. Furthermore, we discuss the clinical management, treatment options, current challenges, and potential novel targeting strategies of metastatic bone disease. Abstract Bone metastasis is a frequent complication of breast cancer with nearly 70% of metastatic breast cancer patients developing bone metastasis during the course of their disease. The bone represents a dynamic microenvironment which provides a fertile soil for disseminated tumor cells, however, the mechanisms which regulate the interactions between a metastatic tumor and the bone microenvironment remain poorly understood. Recent studies indicate that during the metastatic process a bidirectional relationship between metastatic tumor cells and the bone microenvironment begins to develop. Metastatic cells display aberrant expression of genes typically reserved for skeletal development and alter the activity of resident cells within the bone microenvironment to promote tumor development, resulting in the severe bone loss. While transcriptional regulation of the metastatic process has been well established, recent findings from our and other research groups highlight the role of the autophagy and secretory pathways in interactions between resident and tumor cells during bone metastatic tumor growth. These reports show high levels of autophagy-related markers, regulatory factors of the autophagy pathway, and autophagy-mediated secretion of matrix metalloproteinases (MMP’s), receptor activator of nuclear factor kappa B ligand (RANKL), parathyroid hormone related protein (PTHrP), as well as WNT5A in bone metastatic breast cancer cells. In this review, we discuss the recently elucidated mechanisms and their crosstalk with signaling pathways, and potential therapeutic targets for bone metastatic disease.

Venous thromboembolism (VTE) is a common morbidity in trauma patients. Standard VTE chemoprophylaxis is often inadequate. We hypothesized that weight-based dosing would result in appropriate prophylaxis more reliably than fixed dosing. All patients admitted to a Level 1 trauma center over a 6-month period were included unless contra-indications for VTE prophylaxis existed. A prospective adjusted-dosing group was compared to a retrospective uniform-dosing group. The adjusted-dosing approach consisted of initial weight-based dosing of 0.5 mg/kg subcutaneously (subQ) every 12 h (q12h). Peak anti-factor Xa was measured. Patients outside of the prophylactic range had their dose adjusted by ± 10 mg. The uniform-dosing group received 30 mg subQ q12h, without adjustments. Eighty-four patients were included: 44 in the retrospective control cohort and 40 in the prospective experimental cohort. More patients were sub-prophylactically dosed in the uniform-dosing group relative to the adjusted-dosing group (25% vs 5%, p = 0.03). There was no difference in overall prophylactic range targeting, because the supra-prophylactically dosed patients in the adjusted-dosing group eliminated the effect (p = 0.173). However, after a single dose adjustment, zero patients were outside of prophylactic range (25% versus 0%, RR = infinite, p = 0.003). In the uniform-dosing group, anti-Xa level correlated with body surface area (BSA; R2 = 0.33, p

BACKGROUNDA federal assault weapons ban has been proposed as a way to reduce mass shootings in the United States. The Federal Assault Weapons Ban of 1994 made the manufacture and civilian use of a defined set of automatic and semiautomatic weapons and large capacity magazines illegal. The ban expire

Background: There is high prevalence of diabetes mellitus in patients of end stage liver disease and it has been implicated for complications in post-transplant patients. Glycated hemoglobin is now targeted as a modifiable preoperative risk factors for postoperative complications. Data describing the course and severity of postoperative liver transplant complication and their relation with pre-operative glycated hemoglobin level is sparse. In this study, we looked for co-relation between the preoperative HbA1c level and post-operative mortality and morbidity in patients scheduled for liver transplant. Materials and Methods: Retrospective data in 400 adult patients operated for liver transplant were retrieved. After exclusion, data were analyzed for 224 patients. Patients were divided into two groups on the basis of glycated hemoglobin levels (Group 1 (HbA1C ≥6.5) and Group 2 (HbA1C

The COVID-19 pandemic created an unprecedented strain on hospitals in New York City. Although practitioners focused on the pulmonary devastation, resources for the provision of dialysis proved to be more constrained. To deal with these shortfalls, NYC Health and Hospitals/Bellevue, NYU Brooklyn, NYU Medical Center and the New York Harbor VA Healthcare System, put together a plan to offset the anticipated increased needs for kidney replacement therapy.Prior to the pandemic, peritoneal dialysis was not used for acute kidney injury at Bellevue Hospital. We were able to rapidly establish an acute peritoneal dialysis program at Bellevue Hospital for acute kidney injury patients in the intensive care unit. A dedicated surgery team was assembled to work with the nephrologists for bedside placement of the peritoneal dialysis catheters. A multi-disciplinary team was trained by the lead nephrologist to deliver peritoneal dialysis in the intensive care unit. Between April 8, 2020 and May 8, 2020, 39 peritoneal dialysis catheters were placed at Bellevue Hospital. 38 patients were successfully started on peritoneal dialysis. As of June 10, 2020, 16 patients recovered renal function. One end stage kidney disease patient was converted to peritoneal dialysis and was discharged. One catheter was poorly functioning, and the patient was changed to hemodialysis before recovering renal function. There were no episodes of peritonitis and nine incidents of minor leaking, which resolved. Some patients received successful peritoneal dialysis while being ventilated in the prone position.In summary, despite severe shortages of staff, supplies and dialysis machines during the COVID-19 pandemic, we were able to rapidly implement a de novo peritoneal dialysis program which enabled provision of adequate kidney replacement therapy to all admitted patients who needed it. Our experience is a model for the use of acute peritoneal dialysis in crisis situations.

Background Breast cancer is the most commonly diagnosed cancer among women and its metastases results in poor survival rates in patients. The ability to alter metabolism is a key attribute cancer cells use to survive within different metastatic microenvironments and cause organ failure. We hypothesized that evaluation of metabolic alterations within tumor cells could provide a better understanding of cancer metastasis. Therefore, to investigate underlying metabolic alterations during metastases, we utilized human MDA-MB-231 and mouse 4T1 models that closely mimic human breast cancer metastasis. Methods The glycolysis and glutamine pathway-related changes were examined in bone metastatic cells by XF-24 extracellular flux analyzer and western blotting. The expression levels of genes related to metabolism were examined by PCR arrays. Results The MDA-MB-231 cells isolated after bone metastases showed reduced glucose uptake and glycolysis compared to parental cells, suggesting that these cells could alter metabolic requirements for survival. To understand these metabolic changes, we investigated glutamine, a common and naturally occurring non-essential amino acid. Interestingly, in reduced glucose conditions both cell lines showed dependence on glutamine for cell survival, and with glutamine withdrawal significantly increasing apoptotic cell death. Glutamine was also critical for normal cell proliferation even in the presence of high glucose concentrations. To further understand this metabolic switch in metastatic cells, we examined the genes related to metabolism and identified a more than seven-fold downregulation of protein kinase C zeta (PKC-ζ) expression levels in bone-derived MDA-MB-231 cells compared to the parental population. The PKC-ζ levels were also significantly reduced in metastatic 4T1 cells compared to non-metastatic MT1A2 cells. Since PKC-ζ deficiency promotes glutamine utilization via the serine biosynthesis pathway, we examined glutamine metabolism. The ectopic expression of PKC-ζ inhibited glutamine conversion to glutamate, while mutant PKC-ζ reversed this effect. Furthermore, the gene expression levels of enzymes involved in serine biosynthesis, phosphoserine phosphatase (PSPH), phosphoserine aminotransferase (PSAT1), and phosphoglycerate dehydrogenase (PHGDH) showed upregulation following glucose deprivation with PKC-ζ deficiency. The PHGDH upregulation was inhibited by ectopically expressing wild type but not mutated PKC-ζ in glucose-deprived conditions. Conclusions Our results support the upregulation of serine biosynthesis pathway genes and downregulation of PKC-ζ as potential metabolic alterations for bone metastatic breast cancer cells.

Health-care disparities based on race and socioeconomic status among trauma patients are well-documented. However, the influence of these factors on the management of rib fractures following thoracic trauma is unknown. The aim of this study is to describe the association of race and insurance status on management and outcomes in patients who sustain rib fractures.The Trauma Quality Improvement Program database was used to identify adult patients who presented with rib fractures between 2015 and 2016. Patient demographics, injury severity, procedures performed, and outcomes were evaluated. Multivariate logistic regression analysis was used to determine the effect of race and insurance status on mortality and the likelihood of rib fixation surgery and epidural analgesia for pain management.A total of 95,227 patients were identified. Of these, 2923 (3.1%) underwent rib fixation. Compared to White patients, Asians (AOR: 0.57, P = 0.001), Blacks or African-Americans (AA) (AOR: 0.70, P 0.001), and Hispanics/Latinos (HL) (AOR: 0.78, P 0.001) were less likely to undergo rib fixation surgery. AA patients (AOR: 0.67, P = 0.004), other non-Whites (ONW) (AOR: 0.61, P = 0.001), and HL (AOR 0.65, P = 0.006) were less likely to receive epidural analgesia. Compared to privately insured patients, mortality was higher in uninsured patients (AOR: 1.72, P 0.001), Medicare patients (AOR: 1.80, P 0.001), and patients with other non-private insurance (AOR: 1.23, P 0.001).Non-White race is associated with a decreased likelihood of rib fixation and/or epidural placement, while underinsurance is associated with higher mortality in patients with thoracic trauma. Prospective efforts to examine the socioeconomic disparities within this population are warranted.

Background: While mass-casualty incidents (MCIs) may have competing absolute definitions, a universally accepted criterion is one that strains locally available resources. In the fall of 2017, a MCI occurred in New York and Bellevue Hospital received multiple injured patients within minutes; lessons learned included the need for a formalized, efficient patient and injury tracking system. Our objective was to create an organized MCI clinical tracking form for civilian trauma centers.Methods: After the MCI, the notes of the surgeon responsible for directing patient triage were analyzed. A succinct, organized template was created that allows MCI directors to track demographics, injuries, interventions, and other important information for hmultiple patients in a real-time fashion. This tool was piloted during a subsequent MCI.Results: In late 2018, the hospital received six patients following another MCI. They arrived within a 4-minute window, with 5 patients being critically injured. Two emergent surgeries and angioembolizations were performed. The tool was used by the MCI director to prioritize and expedite care. All physicians agreed that the tool assisted in organizing diagnostic and therapeutic triage. Conclusions: During MCIs, a streamlined patient tracking template assists with information recall and communication between providers and may allow for expedited care.

This study evaluated the safety of early anti-factor Xa assay-guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay-guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.

BACKGROUND Malnutrition affects 40%-90% of patients with cirrhosis of the liver. L3 skeletal muscle index (L3SMI) is presently accepted as the most objective and quantitative measure available for sarcopenia, a surrogate marker of malnutrition. L3SMI application is, however, limited by non-availability of computed tomography scanning in remote areas, cost, need for extensive training, and the risk of exposure to radiation. Therefore, an alternative dependable measure with wider availability is needed. Malnutrition causes sarcopenia not only in skeletal muscles but also in other muscular structures such as the psoas muscle, diaphragm and tongue. We therefore hypothesised that the tongue, being easily accessible for inspection and for measurement of thickness using ultrasonography, may be used to document sarcopenia. AIM To measure and compare tongue thickness in healthy individuals and in patients with cirrhosis of the liver and to study its correlation with conventional prognostic scores for patients with cirrhosis of the liver. METHODS Tongue thickness was measured using ultrasonography. One hundred twenty subjects of either gender aged 18 to 65 years were studied, with 30 subjects in each group. The tongue thickness was compared between groups based on "Child Turcotte Pugh" (CTP) scores. The correlations between measured tongue thickness and "Model for end stage liver disease" (MELD) score and between age and measured tongue thickness were also assessed. RESULTS Mean tongue thickness (mean ± SD) in patients with CTP class A, B and C was 4.39 ± 0.39 cm, 4.19 ± 0.53 cm, and 3.87 ± 0.42, respectively, and was 4.33 ± 0.49 cm in normal healthy individuals. Significant differences were seen in tongue thickness between patients with CTP class C and those with CTP class A and B (P < 0.05). Patients with CTP class C also had a significantly reduced tongue thickness than normal individuals (P < 0.05). However, no significant difference was seen in tongue thickness between patients with CTP class A and B and normal individuals. A statistically significant, negative correlation was found between MELD score and tongue thickness (r = -0.331) (P < 0.001). No correlation was observed between L3SMI and MELD score (r = 0.074, P = 0.424). L3SMI (mean ± SD) in healthy subjects was 39.66 ± 6.8 and was 38.26 ± 8.88 in patients with CTP class C, and the difference was not significant. No significant correlation was found between age of the patients and tongue thickness. Intra-class correlation coefficient was used to determine the reliability of the tongue thickness measurements. The intra-class correlation coefficient was 0.984 (95%CI: 0.979-0.989) and was indicative of good reliability. CONCLUSION Tongue thickness measured by ultrasonography, correlates significantly with the severity of liver disease, as assessed by CTP and MELD scores. The patients with a CTP score ≥ 10 have significantly reduced tongue thickness as compared to normal individuals and those with less severe liver disease and CTP scores of 5-9. No significant difference in tongue thickness was found between healthy individuals and CTP class A and B patients.

Purpose To evaluate the safety and efficacy of a deferred laser treatment after intravitreal bevacizumab (IVB) monotherapy in cases of severe retinopathy of prematurity (ROP) infants. Design Retrospective study. Participants Infants diagnosed with severe ROP, i.e., aggressive posterior ROP (APROP) and ROP in zone 1 and zone 2 posterior with plus disease. Methods Infants diagnosed with severe ROP received immediate IVB. Laser photocoagulation was done, at which time anterior growth of the vessels was arrested. This was seen clinically either with the formation of a demarcation line or when no growth of vessels was seen subjectively on 2 subsequent clinical examinations over a period of 2 weeks. Main Outcome Measures Primary outcome measures were the ability to prevent ROP recurrence and the anatomic outcome at the last follow-up visit. Results Of the 3792 patients screened, 14 patients (28 eyes) were diagnosed with APROP and 15 patients (30 eyes) were diagnosed with ROP in zone 1 and zone 2 posterior with plus disease. Neovascularization of the iris was noted in 4 eyes of 3 patients. The mean postmenstrual age at which IVB was given was 35.0±2.4 weeks (range, 28–40 weeks). ROP along with neovascularization of the iris regressed in all eyes at the next follow-up at 2 weeks. Recurrence of ROP was noted in 4 eyes of 2 patients (6.8%). Both patients had APROP initially. The adjusted age at which recurrence occurred was 35.0±2.8 weeks (range, 33–37 weeks) and laser treatment was done at the adjusted age of 44.0±4.2 weeks. The mean duration between IVB and laser was 9.0±7.1 weeks (range, 4–14 weeks). The mean follow-up was 13.1±1.5 months (range, 12–18 months). None of the eyes developed recurrence after laser treatment in the 1-year follow-up period. None of the patients developed an unfavorable anatomic outcome. Conclusions In our small series, using our treatment protocol, devastating complications and associated blindness related to reactivation of the disease were not seen. Our proposed protocol of IVB monotherapy with deferred laser treatment can be used in severe ROP patients with poor compliance.

Background and Objectives: The present study was designed to explore the utility of ultrasound-guided diaphragmatic thickness in the preoperative period in healthy controls scheduled for live-related donor hepatectomy and patients suffering from chronic liver disease scheduled for liver transplantation (LT) and its use as a predictor of postoperative weaning failure. Materials and Methods: This prospective observational study was conducted in a tertiary health care center and 65 adult (18–70 years) participants (30 healthy liver donors and 35 liver transplant recipients) were enrolled for this study. Right diaphragmatic thickness of both donors and recipients was measured by B-mode ultrasound using a 10 MHz linear array transducer in the supine position in the operation theater just before induction of anesthesia. For subgroup analysis of the recipients, we further divided them into two groups – Group 1 (diaphragmatic thickness < 2 mm) and Group 2 (diaphragmatic thickness > 2 mm), and comparison was done for duration of mechanical ventilation. Intergroup comparison was made for duration of mechanical ventilation and various other parameters. Results: The sonographic measurement of diaphragm revealed that its thickness is decreased in patients with chronic liver disease patients (2.12 ± 0.54 mm) as compared to healthy donors (3.70 ± 0. 58 mm). On multiple logistic regression, higher duration of mechanical ventilation was associated with diaphragmatic thickness < 2 mm (Group 1 of recipients) (adjusted odds ratio 0.86; 95% confidence interval: 0.75–0.99; P = 0.013) after adjusting for age, gender, and body mass index. Conclusions: Diaphragmatic thickness is decreased in patients with chronic liver disease as compared to healthy liver donors. Preoperative measurement of ultrasound-guided right hemidiaphragm thickness can be used to predict weaning failure in patients undergoing LT. Other studies are needed to confirm these finding on different group of patients.

Heart failure (HF) following liver transplant (LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, echocardiography at rest and on stress, reasonably prognosticates the risk. In patients of chronic liver disease, cirrhotic cardiomyopathy, alcoholic cardiomyopathy, and stress induced cardiomyopathy have each been implicated as a cause for HF after LT. However distinguishing one etiology from another not only is difficult, several etiologies may possibly coexist in a given patient. Diagnostic dilemma is further compounded by the fact that presentation and management of HF irrespective of the possible underlying cause, remains the same. In this case series, 6 cases are presented and in the light of existing literature modification in the preoperative workup are suggested.

Lung cancer is the leading cause of cancer-related mortality worldwide. The five-year survival rate is very low in lung cancer patients due to diagnosis at late stages, tumor recurrence, and drug resistance. Recent studies suggest that cancer cells with self-renewal capacity contribute to tumor growth. Identification of reliable markers for cancer stem cell populations and mechanistic understanding of associated signaling pathways and regulatory factors are critically needed to improve long-term survival. Several studies have established the expression of stem cell markers (aldehyde dehydrogenase ALDH1, glycoprotein CD44 and CD133) in lung cancer cell lines and clinical samples. Association of these stem cell markers with lung cancer and the signaling pathways (Wnt, Notch, and Hedgehog) maintaining stem cell characteristics are briefly reviewed here. Interestingly, epigenetic mechanisms and regulatory roles of transcription factors such as Sox2 and Runx family members have been shown to contribute to stem cell properties and lung cancer. Understanding mechanisms regulating “stemness” and differentiation of lung epithelial cells will lead to novel therapies for successful targeting of cancer stem cells.

In the United States in 2013, nearly 500,000 bicyclists were injured and required emergency department care. The objectives of this study were to describe the types of injuries which urban bicyclists sustain, to analyze the number and type of surgeries required, and to better delineate the services providing care. This is an observational study of injured bicyclists presenting to a Level I trauma center between February 2012 and August 2014. Most data were collected within 24 hours of injury and included demographics, narrative description of the incident, results of initial imaging studies, Injury Severity Score, admission status, length of stay, surgical procedure, and admitting and discharging service. A total of 706 injured bicyclists were included in the study, and 187 bicyclists (26.4%) required hospital admission. Of those admitted, 69 (36.8%) required surgery. There was no difference in gender between those who required surgery and those who did not (P = 0.781). Those who required surgery were older (mean age 39.1 vs 34.1, P = 0.003). Patients requiring surgery had higher Abbreviated Injury Scores for head (P ≤ 0.001), face (P ≤ 0.001), abdomen (P = 0.012), and extremity (P ≤ 0.001) and higher mean Injury Severity Scores (12.6 vs 3.7, P < 0.001). Sixty-nine patients required surgery and were brought to the operating room 82 times for 89 distinct procedures. Lower extremity injuries were the reason for 43 (48.3%) procedures, upper extremity injuries for 14 (15.7%), and facial injuries for 15 (16.9%). Orthopedic surgery performed 50 (56.2%) procedures, followed by plastic surgery (15 procedures; 16.8%). Trauma surgeons performed five (5.6%) procedures in four patients. The majority of admitted patients were admitted and discharged by the trauma service (70.1%, 56.7%, respectively) followed by the orthopedics service (13.9%, 19.8%, respectively). Injured bicyclists represent a unique subset of trauma patients. Orthopedic surgeons are most commonly involved in their operative management and rarely are the operative skills of a general traumatologist required. From a resource perspective, it is more efficient to direct the inpatient care of bicyclists with single-system trauma to the appropriate surgical subspecialty service soon after appropriate initial evaluation and treatment by the trauma service.

Background & objectives: Coagulation and haemostasis are dynamic processes. The haemostatic changes in liver disease affect all aspects of coagulation. The prothrombin time (PT)/ international normalized ratio (INR) was developed to monitor oral anticoagulant therapy and the activated partial thromboplastin time to investigate inheritable single factor deficiencies. Viscoelastic tests such as thromboelastogram (TEG) give information about dynamics of clot formation (coagulation factor and anticoagulant activity), clot strength (platelets and fibrinogen) and clot stability (finbrinolysis and factor XIII). Administration of blood products before invasive procedures is still guided by INR and platelet count in patients of liver disease. This study was aimed to evaluate the validity of TEG to predict post-procedural bleed after central venous cannulation in patients with cirrhosis. Methods: Ninety patients aged 20-70 yr diagnosed with liver cirrhosis requiring elective central venous catheter (CVC) insertion were studied. Platelet count, INR, serum creatinine, TEG and Child-Turcotte-Pugh (CTP) score were recorded before the procedure. Right-sided internal jugular vein was cannulated. On the basis of presence or absence of post-procedural bleed, patients were divided into bleeding and non-bleeding groups. The CTP score, component of TEG (R - reaction time, K - coagulation time, MA - maximum amplitude and α - angle) and laboratory parameters of both the groups were compared. Results: Bleeding was seen more when CTP scores were ≥10 (P=0.05). The K time of 3.05 min or more on thromboelastograph was a significant predictor of bleeding [area under the curve (AUC) 0.694, P=0.047]. MA of 48.8 mm or more was a significant predictor of non-bleeding. INR ≥2.6 was a significant predictor of bleeding (AUC 0.765, P=0.005). K time had a low-positive predictive value of 20 per cent and the positive and negative likelihood ratios of 1.87 and 0.48, respectively. Interpretation & conclusions: Our results show that the cut-off value for INR ≥2.6 and K time ≥3.05 min predict bleeding and MA ≥48.8 mm predicts non-bleeding in patients with cirrhosis undergoing central venous pressure catheter cannulation.

Thromboelastography provides a holistic picture of blood coagulation including fibrin formation, cross, linking and fibrinolysis. Coagulaopathy in end stage renal disease (ESRD) is multifactorial. The present evaluated the thromboelastographic profile of ESRD patients and compared it to conventional tests of coagulation.In this observational case control study, fifty ESRD patients and 50 controls were recruited. Venous samples were withdrawn and platelet count, International Normalization Ratio and fibrinogen levels were measure. Simultaneously a thromboelastography (TEG) was performed. All samples were drawn prior to initiation of dialysis.The fibrinogen concentration was higher in the ESRD group compared to control (455.51±83.39 vs. 233.84±71.71 mg/dl, P0.05). The maximum amplitude in ESRD group was 76.94 ± 15.11 mm, which was significantly higher than control group 65.10±10.31 mm (P0.05).Out of 50 ESRD patients,39 had maximum amplitude (MA)73mm, 3 had MA55 mm while 8 patients had normal MA. Further, it was seen that in four out if the five patients whose INR was greater than 1.5. TEG was hypercoaguable. Also, three patients whose platelet count was less than x105/dl had normal thromboelastographs. Two patients with normal platelet count, fibrinogen and INR had hypercoaguable thromboelastographs. Thromboelastography could detect fibrinolysis in 5 patients of end stage renal disease.The present study demonstrated that INR, platelet count and fibrinogen levels do not reflect the actual coagulation status in patients of ESRD. Thromboelastography is a better tool to detect coagulopathy in this group of patients.

Venous thromboembolism (VTE) is a common morbidity in trauma patients. Standard VTE chemoprophylaxis is often inadequate. We hypothesized that weight-based dosing would result in appropriate prophylaxis more reliably than fixed dosing.All patients admitted to a Level 1 trauma center over a 6-month period were included unless contra-indications for VTE prophylaxis existed. A prospective adjusted-dosing group was compared to a retrospective uniform-dosing group. The adjusted-dosing approach consisted of initial weight-based dosing of 0.5 mg/kg subcutaneously (subQ) every 12 h (q12h). Peak anti-factor Xa was measured. Patients outside of the prophylactic range had their dose adjusted by ± 10 mg. The uniform-dosing group received 30 mg subQ q12h, without adjustments.Eighty-four patients were included: 44 in the retrospective control cohort and 40 in the prospective experimental cohort. More patients were sub-prophylactically dosed in the uniform-dosing group relative to the adjusted-dosing group (25% vs 5%, p = 0.03). There was no difference in overall prophylactic range targeting, because the supra-prophylactically dosed patients in the adjusted-dosing group eliminated the effect (p = 0.173). However, after a single dose adjustment, zero patients were outside of prophylactic range (25% versus 0%, RR = infinite, p = 0.003). In the uniform-dosing group, anti-Xa level correlated with body surface area (BSA; RWeight-based VTE prophylaxis with anti-Xa-based dose adjustment improves prophylactic range targeting relative to uniform dosing and eliminates variances secondary to BSA and weight in trauma patients.

Hepatoid adenocarcinoma (HA) is a rare malignant tumor of extrahepatic origin that morphologically and immunophenotypically resembles hepatocellular carcinoma. We report a case of rectal HA with hepatic metastasis arising in a 38-year-old male with a history of ulcerative colitis. Despite elevated alpha-fetoprotein, contrast enhancement of the hepatic mass was not consistent with hepatocellular carcinoma. Immunohistochemistry revealed the diagnosis, and the patient was started on palliative chemotherapy. Colorectal HA should be considered when evaluating malignant lesions in the setting of inflammatory bowel disease and can be distinguished from other tumors based on alpha-fetoprotein, imaging, and immunostaining.

The mechanisms underlying reprogramming of growth factor signaling and metabolic pathways during bone metastasis of breast cancer are not clear. The Runt-related transcription factor (Runx2) regulates cell signaling during mammary epithelial morphogenesis and promotes invasion; therefore, we investigated its role in cell growth and metabolic signaling in bone-seeking breast cancer cells. We performed systemic inoculation of control or Runx2 knockdown invasive MDA-MB-231 cells in NOD/SCID mice, and compared parental and bone-derived variants for phenotypic and molecular alterations. The Runx2 knockdown showed early (0-2 weeks) inhibition of metastatic spread but late (4-6 weeks) outgrowth, suggesting Runx2-dependent bi-phasic response and reprogramming of metastatic cells. The late-stage tumor outgrowth of bone-derived Runx2 knockdown cells was associated with increased insulin-like growth factor- 1Rβ (IGF-1Rβ) levels. Interestingly, glucose uptake and glycolysis were reduced in the bone-derived Runx2 knockdown cells that could be further reduced by extracellular-regulated protein kinase (Erk1/2) inhibition. Furthermore, the Runx2 knockdown cells displayed activation of AMP-activated protein kinase (AMPKα), the sensor of cellular metabolism. Importantly, the Runx2 knockdown in bone-derived cells resulted in increased sensitivity to both Erk1/2 inhibition and AMPKα activation by PD184161 and metformin, respectively, despite increased IGF-1Rβ and AMPKα levels. Our results reveal that Runx2 promotes metastatic spread of mammary tumor cells. The growth of late-stage tumor cells can be targeted by Runx2 knockdown in combination with Mek-Erk1/2 inhibition and metformin treatment.

Background and Aims: De novo hypertension (HTN) in liver transplantation recipients is a known entity. We investigated haemodynamic behaviour after a liver transplant to see if it can predict survival to discharge from the hospital. Methods: electronic records of Haemodynamic parameters and laboratory investigations of 95 patients of living donor liver transplant (LDLT) were retrospectively analysed. Results: Twenty-three patients were operated for acute liver failure (ALF) and 72 patients for chronic liver disease (CLD). Eight patients of CLD and four of ALF did not survive. CLD patients had statistically significant rise in systolic blood pressure from the post-operative day (POD) 1 to POD 4 and diastolic blood pressure (DBP) from POD 3 to POD 6. Heart rate (HR) significantly decreased from POD 3 to POD 5. Haemodynamic parameters returned to baseline values within 20 days. Diastolic HTN had a positive predictive value of 100% for survival with 100% sensitivity and specificity. Systolic HTN had a positive predictive value of 100% for survival (sensitivity-89%, specificity-100%). ALF patients had a significant decrease in HR from POD 2 to POD 10. Bradycardia (HR ≤60/min) had a positive predictive value of 100% for survival with a sensitivity of 45% and 58% in CLD and ALF, respectively, with a specificity of 100% in both the groups. Non-survivors had no significant change in haemodynamics. In CLD group, International Normalised Ratio had statistically significant, strong negative correlation with DBP. Conclusion: Haemodynamic pattern of recovery may be used for predicting survival to discharge after LDLT.

Bone metastasis of breast cancer causes significant patient mortality. During metastasis, breast cancer cells induce autophagy to survive metabolic stress. Although the core components of the autophagy pathway have been characterized, the regulatory mechanism of autophagy in bone metastatic cancer cells is still unknown. To examine autophagy during bone metastasis, we used a bone metastatic isogenic variant of breast cancer MDA-MB-231 cells isolated from a xenograft tumor mouse model of metastasis. Previously, we and others have shown that Runt-related transcription factor-2 (Runx2) promotes cell survival, cell invasion, and metastatic tumor growth associated osteolysis. Therefore, we examined the regulatory mechanisms of Runx2-mediated autophagy for increased cell survival in the bone microenvironment. Our results show that Runx2 promotes microtubule (MTs) stability to enhance autophagy flux. We show that Runx2 silencing significantly decreases acetylated α-Tubulin (Ac-α-Tub) levels. Ac-α-Tub is a marker of stable MTs, which promotes trafficking of autophagosomes. Ac-α-Tub also increases during cellular stress, such as glucose starvation. We found that Runx2 knockdown cells are able to induce Ac-α-Tub upon glucose starvation but are unable to maintain acetylated polymer mass of MTs upon removal of stress. Furthermore, expression of wild type or transcriptionally inactive Runx2 can restore Ac-polymer of MTs in Runx2 knockdown cells, while C-terminal deletion mutant failed to rescue MT polymer mass. Previous studies have shown that the C-terminal of Runx2 serves a scaffolding function by interacting with MTs and multiple proteins including HDAC6, the deacetylase of α-Tubulin. Interestingly, the expression levels of HDAC6 and αTAT1 (α-tubulin acetyltransferase-1) were not altered with Runx2 silencing, suggesting a transcriptionally independent function for Runx2 for maintaining the MTs stability. As MT targeting agents are often used as chemotherapeutics, we found that treatment with vinblastine, a MT disrupting agent, decreases Ac-polymer MTs with Runx2 silencing or expression of C-terminal mutant Runx2, while WT and transcriptionally inactive Runx2 expressing cells exhibit resistance to the treatment. Conversely, treatment with Docetaxel, a MT stabilizing agent, enhances Ac-α-Tub and polymer MTs. Recent reports have also linked high levels of Ac-α-Tub with aggressive breast cancer. We performed immunohistochemistry for Ac-α-Tub levels in bone metastatic patient samples and found significantly strong Ac-α-Tub positive cells in matched and unmatched bone metastatic tumors compared to the primary tumors. Our findings indicate that inhibition of Runx2 may sensitize metastatic tumors to MT targeting agents, and Runx2 and Ac-α-Tub levels may serve as markers for metastatic tumors to help stratify patients for optimal treatment for bone metastatic tumors. Citation Format: Ahmad Othman, Marcus Winogradzki, Manish Tandon, Jitesh Pratap. Runx2 promotes microtubule stability for survival of breast cancer bone metastatic cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1240.

Background and Aims: Patients with cirrhosis of the liver have high mortality after surgery. We investigated the mortality in patients with cirrhosis of the liver who underwent surgery other than liver transplant and applied the Mayo clinic model to predict mortality and compare with the observed mortality. We also studied the association of the observed mortality with the Child-Turcotte-Pugh (CTP) class and the model for end-stage liver disease (MELD) and model for end-stage liver disease-sodium (MELD-Na) scores. Methods: The electronic records database of our hospital was accessed to analyze the data of 133 cirrhotic patients who underwent various surgeries under general anesthesia from October 2009 to June 2017. The Mayo risk score was applied to each and used to calculate predicted mortality; the MELD and MELD-Na scores were also calculated. Telephonic interview was performed with the patients and or their relative to ascertain survival or time of death after surgery, when the information was not available from the hospital records. Results: The all-cause observed mortality rates at postoperative days 30 and 90 and at 1 year were 12%, 20.3% and 26.3% respectively. The area under the receiver operating characteristic curve values for the Mayo model as a predictor of 30-day, 90-day and 1-year mortality were 0.836, 0.828 and 0.744 respectively. Good correlation was seen for observed mortality with CTP class and with MELD and MELD-Na scores. Conclusions: The Mayo model for predicting postoperative mortality in patients with cirrhosis of the liver demonstrated good correlation in this study. The strength of prediction of mortality by Mayo risk score calculation was similar at postoperative days 30 and 90 but decreased at 1-year after the surgery. Good correlation was seen for the observed mortality with MELD, MELD-Na and CTP scores.