Background and Aims The recruitment and activation of inflammatory cells in the liver delineates the transition from hepatic steatosis to steatohepatitis (SH). Approach and Results We found that in SH, γδT cells are recruited to the liver by C‐C chemokine receptor (CCR) 2, CCR5, and nucleotide‐binding oligomerization domain‐containing protein 2 signaling and are skewed toward an interleukin (IL)‐17A+ phenotype in an inducible costimulator (ICOS)/ICOS ligand–dependent manner. γδT cells exhibit a distinct Vγ4+, PD1+, Ly6C+CD44+ phenotype in SH. Moreover, γδT cells up‐regulate both CD1d, which is necessary for lipid‐based antigens presentation, and the free fatty acid receptor, CD36. γδT cells are stimulated to express IL‐17A by palmitic acid and CD1d ligation. Deletion, depletion, and targeted interruption of γδT cell recruitment protects against diet‐induced SH and accelerates disease resolution. Conclusions We demonstrate that hepatic γδT cells exacerbate SH, independent of IL‐17 expression, by mitigating conventional CD4+ T‐cell expansion and modulating their inflammatory program by CD1d‐dependent vascular endothelial growth factor expression.
Acute gastrointestinal obstruction can have a varied spectrum of clinical presentation and etiologies. It has been studied in detail and the management criteria have been well defined for the most part in our era. The etiologies are usually well defined. However, acute small bowel obstruction (SBO) due to intussusception caused by an inverted Meckel's diverticulum is a rare phenomenon that is often times missed on initial presentation and/or consequently until resected and visualized on pathological examination. We present a case of a 34-year-old presenting with symptoms and signs of acute intestinal obstruction and radiographic exam showing ileo-ileal intussusception. The patient failed to improve initially following conservative management and was taken to the operating room for small bowel resection which then revealed an inverted Meckel’s diverticulum.
Concanavalin-A (Con-A) hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor (CLR) that is critical in the immune response to mycobacteria and fungi, but does not have a well-defined role in pre-clinical models of non-pathogen mediated inflammation. Since 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/EBPβ and 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 CLRs did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ related signaling intermediates, C/EBPβ 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/EBPβ and HIF1-α 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.
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.
BACKGROUND: Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy. OBJECTIVE: This study aimed to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait. DESIGN: This study is a retrospective analysis of data from prospectively maintained databases. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included. INTERVENTION: Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision. MAIN OUTCOMES AND MEASURES: Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group. RESULTS: A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group. LIMITATIONS: Generalizability, sample size, and follow-up duration were limitations of this study. CONCLUSIONS: Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team. See Video Abstract at http://links.lww.com/DCR/B688. CONSERVACIÓN DE ÓRGANOS EN PACIENTES CON CÁNCER DE RECTO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL ANTECEDENTES: Estudios retrospectivos sugieren que observar y esperar es una alternativa segura a la escisión mesorrectal total en pacientes seleccionados con una respuesta clínica completa después de la quimiorradioterapia. OBJETIVO: Determinar la proporción de pacientes con cáncer de recto que pueden beneficiarse de observar y esperar. DISEÑO: Análisis retrospectivo de datos de bases de datos mantenidas de forma prospectiva. ESCENARIO: Centro Oncológico Integral. PACIENTES: Pacientes consecutivos con adenocarcinoma de recto en estadio II o III tratados con TNT utilizando quimioterapia de inducción entre 2012 y 2019 bajo el cuidado del mismo cirujano. INTERVENCIÓN: La terapia neoadyuvante total de tipo inducción consistió en ocho ciclos de leucovorín-fluorouracilo-oxaliplatino o cinco ciclos de capecitabina-oxaliplatino antes de la quimiorradioterapia. A los pacientes con una respuesta clínica completa se les ofreció observar y esperar, y a los pacientes con tumor residual se les ofreció la escisión mesorrectal total. PRINCIPALES RESULTADOS Y MEDIDAS: La respuesta del tumor se evaluó con un tacto rectal, endoscopia y resonancia magnética. Se compararon las características de los pacientes y la supervivencia libre de recurrencia entre el grupo de observación y espera y el grupo de escisión mesorrectal total. RESULTADOS: Se incluyó en el análisis a un total de 88 pacientes. Uno (1%) murió durante la terapia neoadyuvante. Cincuenta y cinco pacientes (62.5%) tuvieron una respuesta clínica incompleta y se sometieron a cirugía; 10 (18%) de los 55 desarrollaron metástasis a distancia y 3 (5%) desarrollaron recidiva local. Los 32 pacientes restantes (36.3%) tuvieron una cCR (respuesta clínica completa) y se sometieron a observar y esperar. En promedio, los pacientes del grupo de observación y espera eran mayores y tenían tumores más pequeños y distales en comparación con el grupo de cirugía. La dosis mediana de radiación, el número de ciclos de quimioterapia, la tasa de eventos adversos y la duración del seguimiento no difirieron sustancialmente entre el grupo de escisión mesorrectal total y el grupo de observación y espera. En el grupo de observación y espera, 2 (6%) pacientes desarrollaron recrecimiento del tumor y uno de ellos tuvo metástasis a distancia. La supervivencia libre de recurrencia fue significativamente mayor en el grupo de observación y espera. LIMITACIONES: Generalizabilidad, tamaño de la muestra, duración del seguimiento. CONCLUSIONES: Aproximadamente un tercio de los pacientes con cáncer de recto en estadio II o III pueden beneficiarse de un abordaje de observación y espera con el objetivo de preservar el recto si se tratan con terapia neoadyuvante total de tipo inducción y son seguidos por un equipo multidisciplinario experimentado. Consulte Video Resumen en http://links.lww.com/DCR/B688.
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.
This case describes an intraoperative incidental finding and surgical removal of ectopic liver tissue attached to the gallbladder during a standard laparoscopic cholecystectomy for acute cholecystitis. These anomalies are rare, with interesting associations and possible clinically relevant complications. The details of the case, along with a brief literature review of embryology, common ectopic sites, and associations/complications, are presented in this paper. Since laparoscopic cholecystectomy is a very common procedure, it is important to increase vigilance of ectopic liver tissues during surgeries to minimize complications and provide optimal management.
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