γδ T Cells Support Pancreatic Oncogenesis by Restraining αß T Cell Activation.

Inflammation is paramount in pancreatic oncogenesis. We identified a uniquely activated γδT cell population, which constituted ∼40% of tumor-infiltrating T cells in human pancreatic ductal adenocarcinoma (PDA). Recruitment and activation of γδT cells was contingent on diverse chemokine signals. Deletion, depletion, or blockade of γδT cell recruitment was protective against PDA and resulted in increased infiltration, activation, and Th1 polarization of αßT cells. Although αßT cells were dispensable to outcome in PDA, they became indispensable mediators of tumor protection upon γδT cell ablation. PDA-infiltrating γδT cells expressed high levels of exhaustion ligands and thereby negated adaptive anti-tumor immunity. Blockade of PD-L1 in γδT cells enhanced CD4(+) and CD8(+) T cell infiltration and immunogenicity and induced tumor protection suggesting that γδT cells are critical sources of immune-suppressive checkpoint ligands in PDA. We describe γδT cells as central regulators of effector T cell activation in cancer via novel cross-talk.

Shifting Perspectives: Equal Blunt Cerebrovascular Risk in Low-Versus High-Energy Cervical Fracture.

INTRODUCTION: Clinical implications of screening for blunt cerebrovascular injury (BCVI) after low-energy mechanisms of injury (LEMI) remain unclear. We assessed BCVI incidence and outcomes in LEMI versus high-energy mechanisms of injury (HEMI) patients. METHODS: In this retrospective cohort study, blunt trauma adults admitted between July 2015 and June 2021 with cervical spine fractures, excluding single spinous process, osteophyte, and chronic fractures were included. Demographics, comorbidities, injuries, screening and treatment data, iatrogenic complications, and mortality were collected. Our primary end point was to compare BCVI rates between LEMI and HEMI patients. RESULTS: Eight hundred sixty patients (78%) were screened for BCVI; 120 were positive for BCVI. LEMI and HEMI groups presented similar BCVI rates (12.6% versus 14.4%; P = 0.640). Compared to HEMI patients (n = 95), LEMI patients (n = 25) were significantly older (79 ± 14.9 versus 54.3 ± 17.4, P < 0.001), more likely to be on anticoagulants before admission (64% versus 23.2%, P < 0.001), and less severely injured (LEMI injury severity score 10.9 ± 6.6 versus HEMI injury severity score 18.7 ± 11.4, P = 0.001). All but one LEMI and 90.5% of the HEMI patients had vertebral artery injuries with no significant difference in BCVI grades. One HEMI patient developed acute kidney injury because of BCVI screening. Eleven HEMI patients developed BCVI-related stroke with two related mortalities. One LEMI patient died of a BCVI-related stroke. CONCLUSIONS: BCVI rates were similar between HEMI and LEMI groups when screening based on cervical spine fractures. The LEMI group exhibited no screening or treatment complications, suggesting that benefits may outweigh the risks of screening and potential bleeding complications from treatment.

Symptomatic, clinical and biomarker associations for mortality in hospitalized COVID-19 patients enriched for African Americans.

BACKGROUND AND AIMS: Initial reports on US COVID-19 showed different outcomes in different races. In this study we use a diverse large cohort of hospitalized COVID-19 patients to determine predictors of mortality. METHODS: We analyzed data from hospitalized COVID-19 patients (n = 5852) between March 2020- August 2020 from 8 hospitals across the US. Demographics, comorbidities, symptoms and laboratory data were collected. RESULTS: The cohort contained 3,662 (61.7%) African Americans (AA), 286 (5%) American Latinx (LAT), 1,407 (23.9%), European Americans (EA), and 93 (1.5%) American Asians (AS). Survivors and non-survivors mean ages in years were 58 and 68 for AA, 58 and 77 for EA, 44 and 61 for LAT, and 51 and 63 for AS. Mortality rates for AA, LAT, EA and AS were 14.8, 7.3, 16.3 and 2.2%. Mortality increased among patients with the following characteristics: age, male gender, New York region, cardiac disease, COPD, diabetes mellitus, hypertension, history of cancer, immunosuppression, elevated lymphocytes, CRP, ferritin, D-Dimer, creatinine, troponin, and procalcitonin. Use of mechanical ventilation (p = 0.001), shortness of breath (SOB) (p < 0.01), fatigue (p = 0.04), diarrhea (p = 0.02), and increased AST (p < 0.01), significantly correlated with death in multivariate analysis. Male sex and EA and AA race/ethnicity had higher frequency of death. Diarrhea was among the most common GI symptom amongst AAs (6.8%). When adjusting for comorbidities, significant variables among the demographics of study population were age (over 45 years old), male sex, EA, and patients hospitalized in New York. When adjusting for disease severity, significant variables were age over 65 years old, male sex, EA as well as having SOB, elevated CRP and D-dimer. Glucocorticoid usage was associated with an increased risk of COVID-19 death in our cohort. CONCLUSION: Among this large cohort of hospitalized COVID-19 patients enriched for African Americans, our study findings may reflect the extent of systemic organ involvement by SARS-CoV-2 and subsequent progression to multi-system organ failure. High mortality in AA in comparison with LAT is likely related to high frequency of comorbidities and older age among AA. Glucocorticoids should be used carefully considering the poor outcomes associated with it. Special focus in treating patients with elevated liver enzymes and other inflammatory biomarkers such as CRP, troponin, ferritin, procalcitonin, and D-dimer are required to prevent poor outcomes.

The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.

Neoplastic pancreatic epithelial cells are believed to die through caspase 8-dependent apoptotic cell death, and chemotherapy is thought to promote tumour apoptosis. Conversely, cancer cells often disrupt apoptosis to survive. Another type of programmed cell death is necroptosis (programmed necrosis), but its role in pancreatic ductal adenocarcinoma (PDA) is unclear. There are many potential inducers of necroptosis in PDA, including ligation of tumour necrosis factor receptor 1 (TNFR1), CD95, TNF-related apoptosis-inducing ligand (TRAIL) receptors, Toll-like receptors, reactive oxygen species, and chemotherapeutic drugs. Here we report that the principal components of the necrosome, receptor-interacting protein (RIP)1 and RIP3, are highly expressed in PDA and are further upregulated by the chemotherapy drug gemcitabine. Blockade of the necrosome in vitro promoted cancer cell proliferation and induced an aggressive oncogenic phenotype. By contrast, in vivo deletion of RIP3 or inhibition of RIP1 protected against oncogenic progression in mice and was associated with the development of a highly immunogenic myeloid and T cell infiltrate. The immune-suppressive tumour microenvironment associated with intact RIP1/RIP3 signalling depended in part on necroptosis-induced expression of the chemokine attractant CXCL1, and CXCL1 blockade protected against PDA. Moreover, cytoplasmic SAP130 (a subunit of the histone deacetylase complex) was expressed in PDA in a RIP1/RIP3-dependent manner, and Mincle--its cognate receptor--was upregulated in tumour-infiltrating myeloid cells. Ligation of Mincle by SAP130 promoted oncogenesis, whereas deletion of Mincle protected against oncogenesis and phenocopied the immunogenic reprogramming of the tumour microenvironment that was induced by RIP3 deletion. Cellular depletion suggested that whereas inhibitory macrophages promote tumorigenesis in PDA, they lose their immune-suppressive effects when RIP3 or Mincle is deleted. Accordingly, T cells, which are not protective against PDA progression in mice with intact RIP3 or Mincle signalling, are reprogrammed into indispensable mediators of anti-tumour immunity in the absence of RIP3 or Mincle. Our work describes parallel networks of necroptosis-induced CXCL1 and Mincle signalling that promote macrophage-induced adaptive immune suppression and thereby enable PDA progression.

Team IHMC at the 2020 Cybathlon: a user-centered approach towards personal mobility exoskeletons.

BACKGROUND: The past few decades have seen rapid advancements in exoskeleton technology, with a considerable shift towards applications involving users with gait pathologies. Commercial devices from ReWalk, Ekso Bionics, and Indego, mainly designed for rehabilitation purposes, have inspired the development of many research platforms aimed at extending capabilities for use as safe and effective personal mobility devices. The 2016 Cybathlon featured an impressive demonstration of exoskeletons designed to enable mobility for individuals with spinal cord injury, however, not a single team completed every task and only two completed the stairs. Major improvements were showcased at the 2020 Cybathlon, with seven of the nine teams completing a similar set of tasks. Team IHMC built upon its silver-medal success from 2016 with an upgraded device, Quix. METHODS: Quix features several notable improvements including an additional powered degree of freedom for hip ab/adduction to laterally shift the device and reduce user effort while walking, custom-tailored cuffs and soft goods based on 3D body scans to optimize user comfort, and a streamlined testing pipeline for online tuning of gait parameters. RESULTS: Team IHMC finished in fourth place behind the teams from EPFL and Angel Robotics. Although we suffered from a considerably slower flat-ground walking speed, our pilot reported marked improvements in overall effort, comfort, and ease-of-use compared to our previous device. CONCLUSIONS: Clear progress in exoskeleton development has been exhibited since the inaugural Cybathlon, with tasks involving rough terrain, stairs, and ramps now posing little threat to most of the competitors. As a result, the layout of the powered exoskeleton course will likely undergo significant modifications to further push the devices towards suitability for personal everyday use. The current tasks do not address the issue of donning and doffing, nor do they simulate a scenario similar to maneuvering a kitchen to prepare a meal, for example. An additional limitation that may be more difficult to test in a competition setting is the required upper-body effort to manipulate the device in an effective manner.

New York Inner City Hospital COVID-19 Experience and Current Data: Retrospective Analysis at the Epicenter of the American Coronavirus Outbreak.

BACKGROUND: In the midst of the coronavirus disease pandemic, emerging clinical data across the world has equipped frontline health care workers, policy makers, and researchers to better understand and combat the illness. OBJECTIVE: The aim of this study is to report the correlation of clinical and laboratory parameters with patients requiring mechanical ventilation and the mortality in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We did a review of patients with SARS-CoV-2 confirmed infection admitted and managed by our institution during the last month. Patients were grouped into intubated and nonintubated, and subgrouped to alive and deceased. A comprehensive analysis using the following parameters were performed: age, sex, ethnicity, BMI, comorbidities, inflammatory markers, laboratory values, cardiac and renal function, electrocardiogram (EKG), chest x-ray findings, temperature, treatment groups, and hospital-acquired patients with SARS-CoV-2. RESULTS: A total of 184 patients were included in our study with ages ranging from 28-97 years (mean 64.72 years) and including 73 females (39.67%) and 111 males (60.33%) with a mean BMI of 29.10. We had 114 African Americans (61.96%), 58 Hispanics (31.52%), 11 Asians (5.98%), and 1 Caucasian (0.54%), with a mean of 1.70 comorbidities. Overall, the mortality rate was 17.39% (n=32), 16.30% (n=30) of our patients required mechanical ventilation, and 11.41% (n=21) had hospital-acquired SARS-CoV-2 infection. Pertinent and statistically significant results were found in the intubated versus nonintubated patients with confirmed SARS-CoV-2 for the following parameters: age (P=.01), BMI (P=.07), African American ethnicity (P<.001), Hispanic ethnicity (P=.02), diabetes mellitus (P=.001), creatinine (P=.29), blood urea nitrogen (BUN; P=.001), procalcitonin (P=.03), C-reactive protein (CRP; P=.007), lactate dehydrogenase (LDH; P=.001), glucose (P=.01), temperature (P=.004), bilateral pulmonary infiltrates in chest x-rays (P<.001), and bilateral patchy opacity (P=.02). The results between the living and deceased subgroups of patients with confirmed SARS-CoV-2 (linking to or against mortality) were BMI (P=.04), length of stay (P<.001), hypertension (P=.02), multiple comorbidity (P=.045), BUN (P=.04), and EKG findings with arrhythmias or blocks (P=.02). CONCLUSIONS: We arrived at the following conclusions based on a comprehensive review of our study group, data collection, and statistical analysis. Parameters that were strongly correlated with the need for mechanical ventilation were younger age group, overweight, Hispanic ethnicity, higher core body temperature, EKG findings with sinus tachycardia, and bilateral diffuse pulmonary infiltrates on the chest x-rays. Those intubated exhibited increased disease severity with significantly elevated levels of serum procalcitonin, CRP, LDH, mean glucose, creatinine, and BUN. Mortality was strongly correlated with BMI, African American ethnicity, hypertension, presence of multiple comorbidities (with a mean of 2.32), worsening renal function with acute kidney injury or acute chronic kidney injury, and EKG findings of arrhythmias and heart blocks.

Mincle Signaling Promotes Con A Hepatitis.

Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPß and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κß-related signaling intermediates C/EBPß and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPß and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

BACKGROUND & AIMS: The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. METHODS: We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. RESULTS: Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. CONCLUSIONS: Radiation treatment causes macrophages murine PDA to acquire an immune-suppressive phenotype and disabled T-cell-mediated anti-tumor responses. MCSF blockade negates this effect, allowing radiation to have increased efficacy in slowing tumor growth.

Hidden Obligatory Fluid Intake in Critical Care Patients.

INTRODUCTION: In addition to the fluid intake in the form of intravenous maintenance or boluses in intensive care unit (ICU) patients, there are sources of fluids that may remain unrecognized but contribute significantly to the overall fluid balance. We hypothesized that fluids not ordered as boluses or maintenance infusions-"hidden obligatory fluids"-may contribute more than a liter to the fluid intake of a patient during any random 24 hours of critical care admission. METHODS: Patients admitted to the Harlem Hospital ICU for at least 24 hours were included in this study (N = 98). Medical records and nursing charts were reviewed to determine the sources and volumes of various fluids for the study patients. RESULTS: The mean hidden obligatory volume for an ICU patient was calculated to be 978 mL (standard deviation [SD]: 904, median: 645) and 1571 mL (SD: 1023, median: 1505), with enteral feeds compared to the discretionary volume of 2821 mL (SD: 2367, median: 2595); this obligatory fluid volume was affected by a patient's need for pressor support and renal replacement therapy. CONCLUSION: Hidden obligatory fluids constitute a major source of the fluid intake among patients in a critical care unit. Up to 1.5 L should be taken into account during daily decision making to effectively regulate their volumes.

African Americans Possessed High Prevalence of Comorbidities and Frequent Abdominal Symptoms, and Comprised A Disproportionate Share of Covid-19 Mortality among 9,873 Us- Hospitalized Patients Early in the Pandemic.

Background and aim: Identifying clinical characteristics and outcomes of different ethnicities in the US may inform treatment for hospitalized COVID-19 patients. Aim of this study is to identify predictors of mortality among US races/ethnicities. Design Setting and participants: We retrospectively analyzed de-identified data from 9,873 COVID-19 patients who were hospitalized at 15 US hospital centers in 11 states (March 2020-November 2020). Main Outcomes and Measures: The primary outcome was to identify predictors of mortality in hospitalized COVID-19 patients. Results: Among the 9,873 patients, there were 64.1% African Americans (AA), 19.8% Caucasians, 10.4% Hispanics, and 5.7% Asians, with 50.7% female. Males showed higher in-hospital mortality (20.9% vs. 15.3%, p=0.001). Non- survivors were significantly older (67 vs. 61 years) than survivors. Patients in New York had the highest in-hospital mortality (OR=3.54 (3.03 - 4.14)). AA patients possessed higher prevalence of comorbidities, had longer hospital stay, higher ICU admission rates, increased requirement for mechanical ventilation and higher in-hospital mortality compared to other races/ethnicities. Gastrointestinal symptoms (GI), particularly diarrhea, were more common among minority patients. Among GI symptoms and laboratory findings, abdominal pain (5.3%, p=0.03), elevated AST (n=2653, 50.2%, p=<0.001, OR=2.18), bilirubin (n=577, 12.9%, p=0.01) and low albumin levels (n=361, 19.1%, p=0.03) were associated with mortality. Multivariate analysis (adjusted for age, sex, race, geographic location) indicates that patients with asthma, COPD, cardiac disease, hypertension, diabetes mellitus, immunocompromised status, shortness of breath and cough possess higher odds of in-hospital mortality. Among laboratory parameters, patients with lymphocytopenia (OR2=2.50), lymphocytosis (OR2=1.41), and elevations of serum CRP (OR2=4.19), CPK (OR2=1.43), LDH (OR2=2.10), troponin (OR2=2.91), ferritin (OR2=1.88), AST (OR2=2.18), D-dimer (OR2=2.75) are more prone to death. Patients on glucocorticoids (OR2=1.49) and mechanical ventilation (OR2=9.78) have higher in-hospital mortality. Conclusion: These findings suggest that older age, male sex, AA race, and hospitalization in New York were associated with higher in-hospital mortality rates from COVID-19 in early pandemic stages. Other predictors of mortality included the presence of comorbidities, shortness of breath, cough elevated serum inflammatory markers, altered lymphocyte count, elevated AST, and low serum albumin. AA patients comprised a disproportionate share of COVID-19 death in the US during 2020 relative to other races/ethnicities.

New perspectives on robotic pancreaticoduodenectomy: An analysis of the National Cancer Database.

BACKGROUND: Pancreatic ductal adenocarcinoma is a common malignancy. Despite all advancements, the prognosis remains, poor with an overall 5-year survival of only 10.8%. Recently, a robotic platform has become an attractive tool for treating pancreatic cancer (PC). While recent studies indicated improved lymph node (LN) harvest during robotic pancreaticoduodenectomy (PD), data on long-term outcomes are insufficient. AIM: To evaluate absolute LN harvest during PD. Secondary outcomes included evaluating the association between LN harvest and short- and long-term oncological outcomes for three different surgical approaches. METHODS: We conducted an analysis of the National Cancer Database, including patients diagnosed with PC who underwent open, laparoscopic, or robotic PD in 2010-2018. One-way analysis of variance was used to compare continuous variables, chi-square test - for categorical. Overall survival was defined as the time between surgery and death. Median survival time was estimated with the Kaplan-Meier method, and groups were compared with the Wilcoxon test. A Cox proportional hazards model was used to assess the association of covariates with survival after controlling for patient characteristics and procedure type. RESULTS: 17169 patients were included, 8859 (52%) males; mean age 65; 14509 (85%) white. 13816 (80.5%) patients had an open PD, 2677 (15.6%) and 676 (3.9%) - laparoscopic and robotic PD respectively. Mean comorbidity index (Charlson-Deyo Score) 0.50. On average, 18.84 LNs were harvested. Mean LN harvest during open, laparoscopic and robotic PD was 18.59, 19.65 and 20.70 respectively (P < 0.001). On average 2.49 LNs were positive for cancer and did not differ by the procedure type (P = 0.26). Vascular invasion was noted in 42.6% of LNs and did differ by the approach: 42.1% for open, 44.0% for laparoscopic and 47.2% for robotic PD (P = 0.015). Median survival for open PD was 26.1 mo, laparoscopic - 27.2 mo, robotic - 29.1 mo (P = 0.064). Survival was associated with higher LN harvest, while higher number of positive LNs was associated with higher mortality. CONCLUSION: Our study suggests that robotic PD is associated with increased intraoperative LN harvest and has comparable short-term oncological outcomes and survival compared to open and laparoscopic approaches.

Traumatic injuries to the trachea and bronchi: a narrative review.

Objective: In this narrative review, we aim to provide a definition of traumatic tracheo-bronchial injuries as well as an approach to their diagnosis and management, including operative and non-operative strategies. Background: Traumatic tracheo-bronchial injuries are relatively uncommon, but are associated with a high mortality, both at the scene and among patients who survive to hospital. Management often requires an emergency airway, usually intubation over a flexible bronchoscope, followed by definitive repair. Methods: The published literature on the diagnosis and management of traumatic airway injuries was searched through PubMed. Additional references were identified from the bibliography of relevant publications identified. The evidence was then summarized in a narrative fashion, incorporating the authors' knowledge, experience, and perspective on the topic. Conclusions: Definitive diagnosis of traumatic tracheo-bronchial injuries usually involves direct visualization through liberal use of bronchoscopy in addition to cross-sectional imaging to evaluate for associated injuries, notably to the great vessels and esophagus. Important considerations for management include concerns for airway obstruction, uncontrolled air leak, and mediastinitis. Early repair of injuries recognized acutely is favored in attempts to prevent the development of airway stenosis. Key operative principles include exposure, conservative debridement to preserve length when possible, creation of a tension-free anastomosis, preservation of the blood supply, and creation of a tracheostomy, particularly in polytrauma patients. An interposition muscle flap is also required, specifically in the setting of combined esophageal and airway injuries. Patients with penetrating injuries tend to have more favorable outcomes, possibly on account of fewer concomitant injuries. Selective non-operative management is also an option in the subset of patients with iatrogenic injuries to the posterior membranous wall of the trachea, and includes broad-spectrum antibiotics and surveillance bronchoscopy.

Gastrointestinal manifestations in American minority population with COVID-19.

BACKGROUND: The spectrum of gastrointestinal (GI) injuries by the SARS-CoV-2 remain largely unknown. Ethnicity data is missing or unspecified. We analyzed GI involvement in American minority patients with COVID-19 infection. METHODS: Retrospective study of hospitalized patients with confirmed COVID-19 in March-April 2020. RESULTS: 183 patients included: 114 (62.30%) African-Americans, 58 (31.69%) Hispanics and 11 (6.01%) Asians. 73 females, 110 males; mean age 64.77, mean BMI 29.03 (50.82%); GI manifestations upon presentation: anorexia (29.51%), diarrhea (22.40%), nausea/vomiting (18.03%), abdominal pain (9.84%). No difference observed between three ethnical groups for GI symptoms and liver function tests. C Reactive Protein (CPR) (P=0.008), Lactate (P=0.03) and Prothrombin Time (PT) (P=0.03) were significantly elevated in patients without GI symptoms. No difference was observed for other laboratory tests. Patients with severe disease course/intubated had higher levels of Aspartate Transaminase (AST) (109.17 vs 53.97, P=0.018), Alanine Transaminase (ALT) (79.53 vs 40.03, P=0.02) and total bilirubin (0.82 vs 0.60, P=0.03) vs non-intubated patents as well as body temperature (101.38 vs 100.70, p=0.0006), CRP (24.06 v 15.96, P=0.019) and lactate (3.28 vs 2.13, P=0.009). There was no correlation between severity of the disease and GI symptoms, PT, platelets and albumin. However, CRP and lactate were markedly elevated in deceased vs survived patients: (27.09 vs 16.39, P=0.008) and (3.33 vs 2.10 P=0.005) respectively. CONCLUSIONS: ~ 50% of patients presented with GI symptoms and they had lower levels of inflammatory markers, better liver synthetic function, indicating less overall inflammatory response and direct viral damage. Our results suggest that SARS-CoV-2 virus targets GI tract along with the lung tissue, and the degree of hepatocyte damage correlated well with more severe disease.

Does C reactive protein/Albumin ratio have prognostic value in patients with COVID-19.

INTRODUCTION: There is paucity of data regarding C reactive protein/Albumin (CRP/Alb) ratio in patients with SARS-CoV-2 infection. We aimed to evaluate the significance of CRP/Alb ratio in COVID-19 patients. METHODOLOGY: Patients hospitalized between March - April 2020 with COVID-19, who had CRP and Albumin levels documented within 24 hours from admission were retrospectively analyzed. Unpaired Student's t-test was used for continuous and Pearson Chi-square (χ²) test for categorical variables. Univariate and multivariate logistic regression models were developed to assess the relationship between CRP/Alb and mortality. Nonparametric correlations were calculated using Spearman's Rho correlation coefficient. RESULTS: 75 patients were included. Mean age was 62.92, 26 females (34.67%) and 49 males (65.33%), mean Body Mass Index (BMI) 29.86, mean body temperature 101.3 and mean length of stay (LOS) was 14.80 days. 24 (32%) patients required invasive mechanical ventilation and 51 (68%) did not, mean CRP/Alb ratio was 6.89 and 4.7 respectively (p = 0.036). 15 (20%) patients died, 60 (80%) survived and the mean CRP/Alb difference between these groups was also statistically significant (7.74 vs 4.83, p = 0.02). LOS (OR 0.71, 95% CI 0.57.-0.88, p < 0.001) and BUN (OR 1.04, 95% CI 1.01.-1.07, p = 0.006) were independent predictors of mortality by multivariate logistic regression, whereas CRP/Alb (OR 1.21, 95% CI 0.96.-1.51, p = 0.06) was not. CONCLUSIONS: CRP/Alb ratio could be useful as a prognostic indicator of disease severity in COVID-19, but we could not corroborate its potential to predict mortality. The work was conducted at Columbia University College of Physicians and Surgeons at Harlem Hospital.

Role of neutrophil-to-lymphocyte, lymphocyte-to-monocyte and platelet-to-lymphocyte ratios as predictors of disease severity in COVID-19 patients.

Direct viral damage and uncontrolled inflammation contribute to disease severity in SARS-CoV-2 infection. The aim of this study was to investigate the prognostic significance of neutrophil-to-lymphocyte [NLR], lymphocyte-to-monocyte [LMR] and platelet-to-lymphocyte [PLR] ratios in COVID-19 patients. All 184 COVID-19 patients hospitalized in our institution between March - April 2020 were retrospectively analyzed. The patients were grouped into intubated and non-intubated, and subgrouped into survived and deceased. An unpaired Student's t-test was used for continuous variables, and the Pearson Chi-square (χ2) test for categorical. Univariate and multivariate logistic regression models were developed to assess the independent relationship between NLR, LMR and PLR and unfavorable outcomes. Non-parametric correlations were calculated using Spearman's Rho correlation coefficient. The mean age of the patients was 64.7; mean BMI was 29.10; 73 (39.67%) were female and 111 male (60.33%). No statistical difference between groups was identified with regard to NLR (mean 8.29, standard deviation [SD] 7.86). On multivariate regression analysis, only PLR and LMR were shown to influence the ratio and it was positively correlated with PLR, lactate and C-reactive protein [CRP]. LMR for non-intubated survived [NI-S] (mean 2.29, SD 1.31) and non-intubated deceased [NI-D] (mean 1.79, SD 0.81) groups were statistically significant (p=0.03). LMR was influenced only by NLR on regression analysis. A positive correlation of LMR with body mass index [BMI] was ascertained. No statistical significance was found between groups for PLR (mean 269.85, SD 207.98) and the ratio was influenced by age and NLR on regression analysis, and positively correlated with NLR. To conclude, previously reported findings of a prognostic role of NLR, LMR and PLR in COVID-19 were not validated in our cohort and we would caution against using the ratios in question as independent markers for disease severity.

Transgender surgery - Knowledge gap among physicians impacting patient care.

Transgender surgeries are increasingly performed across the globe and in the United States. Although comprehensive centers exist, which are well equipped to cater and tailor to the needs of this population subset, quite often their resultant complications are handled at a different institution owing to the acuity of the condition. However, interestingly the psychosocial needs, medical pathophysiology, available surgical procedures, and their resultant complications are still not a part of the regular medical curriculum. This translates into inadequate care when physicians from vast majority of institutions that do not routinely perform transgender surgery encounter these patients with complications from gender-affirming surgeries. We present a case of a patient who underwent complex multiple gender-affirming surgeries, presenting to our emergency department with an acute abdomen; this resulted in a diagnostic and management dilemma and review of brief pertinent literature. We recommend that transgender medicine and its basics needs should be exposed to currently practicing physicians by continuing medical education, trainees and medical students alike via incorporation into their curriculum, to decrease health disparities among the lesbian, gay, bisexual, transgender, and queer community.

Assessing the effect of human dental pulp mesenchymal stem cell secretome on human oral, breast, and melanoma cancer cell lines.

BACKGROUND: The secretome of the dental pulp mesenchymal stem cells (DPMSCS-S) have an array of regenerative potential and could aid in the rehabilitation of cancer patients post-therapeutic interventions, although caution is required as DPMSC-S have shown to augment prostate cancer cells. Thus, it is vital to assess if these pro-carcinogenic effects extend to other cancer types. OBJECTIVE: To assess if DPMSC-S has any pro-carcinogenic effect on oral cancer, breast cancer, and melanoma cell lines. MATERIALS AND METHODS: Conditioned media obtained from the isolated and characterized DPMSC (DPMSC-CM) were profiled using bead-based multiplex assay. AW13515 (oral cancer), MDA-MB-231 (breast cancer), and A-375 (melanoma) cell lines were exposed to 20%, 50%, and 100% DPMSC-CM for 24, 48, and 72 h. DPMSC-CM effect on the cancer cell properties and secretome were assessed. RESULTS: DPMSC-CM augmented invasion, adhesion, multi-drug resistance, DNA repair, and mitochondrial repair in AW13516 through upregulation of growth factors Ang-2, EGF, M-CSF, PDGF-AA, PDGF-BB, pro-inflammatory cytokines TNF-α, IL-2, downregulation of anti-inflammatory cytokine TGF-ß1, and pro-inflammatory cytokine IL-4. In MDA-MB-231, invasion, and multi-drug resistance were augmented through upregulation of growth factors EGF, EPO, G-CSF, HGF, M-CSF, PDGF-AA, and pro-inflammatory cytokine TNF-α, CXCL10, IL-12p70. EMT, invasion, migration, and adhesion were augmented in A-375 through upregulation of growth factors Ang-2, EGF, PDGF-BB, TGF-α, pro-inflammatory cytokines TNF-α, and IL-17A. CONCLUSION: DPMSC-CM can augment the carcinogenic properties of oral cancer, breast cancer, and melanoma cells, further animal model studies are required to validate our in-vitro findings.