The Use of Noninvasive Scores in Predicting NAFLD Progression After Bariatric Surgery.

BACKGROUND: Bariatric surgery has been postulated to impact liver function resulting in favorable effects on nonalcoholic fatty liver disease (NAFLD). We aimed to analyze the long-term impact of bariatric surgery on noninvasive scores predicting the progression of liver fibrosis in a bariatric population. METHODS: We retrospectively reviewed the records of patients without pre-existing liver disease who underwent sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) at our center between 2010 and 2018. Four predictive scores for liver fibrosis (AST/ALT, APRI, Fib-4, and BARD) were calculated preoperatively, 6 months post-operatively, and annually up to 5 years. Correlations were analyzed with Pearson R. Subgroup and sensitivity analyses were performed to identify populations at increased risk. RESULTS: A total of 2769 patients were included. The mean age was 40 years, and the majority was females (88.5%) and of Hispanic ethnicity (59.2%). There was a steady post-operative increase in the percentage of patients at increased risk of progression of liver fibrosis. The Fib-4 score showed the largest increase in the population at risk for liver fibrosis (11.3% preoperatively to 28.9% at 5 years). Patients with diabetes and those who underwent a sleeve gastrectomy continued to display a higher risk for liver fibrosis than did patients without diabetes and those who underwent RYGB, respectively. CONCLUSION: There was an overall trend to increased liver fibrosis scores over the 5-year post-operative follow-up, but this increase remained lower than that reported in previous literature. Bariatric surgery offers NAFLD risk reduction in a high-risk population.

Comparative outcomes of bariatric surgery in patients with ESRD on dialysis in the modern era of renal transplantation: analysis using the 2015-2020 MBSAQIP database.

BACKGROUND: Severe obesity is a relative contraindication for renal transplantation, therefore bariatric surgery is an important option as a pre-kidney transplant weight loss strategy. However, comparative data regarding postoperative outcomes of laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) in patients with or without ESRD on dialysis are scarce. METHODS: Patients between 18- and 80-year-old who underwent LSG and RYGB were included. To determine the outcomes of patient who underwent bariatric surgery with ESRD on dialysis, a 1:4 PSM was performed between the patients with ESRD on dialysis and those without renal disease. The PSM analyses in both groups were performed using 20 preoperative characteristics. Then 30-day postoperative outcomes were assessed. RESULTS: The operative time and postoperative-LOS were significantly longer in ESRD patients on dialysis compared to those with no renal disease either for LSG (82.37 ± 40.42 vs. 73.62 ± 38.65; P < 0.001, 2.22 ± 3.01 vs. 1.67 ± 1.90; P < 0.001) or for LRYGB (129.13 ± 63.20 vs. 118.72 ± 54.16; P = 0.002, 2.53 ± 1.74 vs. 2.00 ± 1.68; P < 0.001). In the LSG cohort (2137 vs. 8495 matched cases), patients with ESRD on dialysis showed significant increase in mortality (0.7% vs 0.3%; P = 0.019), unplanned ICU admission (3.1% vs 1.3%; P < 0.001), blood transfusions (2.3% vs 0.8%; P 0.001), readmissions (9.1% vs. 4.0%; P < 0.001), reoperations (3.4% vs. 1.2%; P < 0.001), interventions (2.3% vs. 1.0%; P = 0.006). In the LRYGB group (443 vs. 1769 matched cases), patients with ESRD on dialysis showed a significantly higher need for unplanned ICU admission (3.8% vs. 1.4%; P = 0.027), readmissions (12.4% vs. 6.6%; P = 0.011), and interventions (5.2% vs. 2.0%; P = 0.050). CONCLUSION: Bariatric surgery is a safe procedure for patients with ESRD on dialysis to help them get a kidney transplant. Even though this group experienced a higher incidence of postoperative complications compared to those without kidney disease, the absolute complication rates are low and not associated with bariatric-specific complications. Therefore, ESRD should not be perceived as contraindications to bariatric surgery.

Factors Predictive of Mortality among Geriatric Patients Sustaining Low-Energy Blunt Trauma.

Background: In geriatric trauma patients, higher mortality rate is observed compared to younger patients. A significant portion of trauma sustained by this age group comes from low-energy mechanisms (fall from standing or sitting). We sought to investigate the outcome of these patients and identify factors associated with mortality. Methods: A retrospective review of 1285 geriatric trauma patients who came to our level 1 trauma center for trauma activation (hospital alert to mobilize surgical trauma service, emergency department trauma team, nursing, and ancillary staff for highest level of critical care) after sustaining low-energy blunt trauma over a 1-year period. IRB approval was obtained, data collected included demographics, vital signs, laboratory data, injuries sustained, length of stay and outcomes. Patients were divided into three age categories: 65−74, 75−84 and >85. Comorbidities collected included a history of chronic renal failure, COPD, Hypertension and Myocardial Infarction. Results: 1285 geriatric patients (age > 65 years) presented to our level 1 trauma center for trauma activation with a low-energy blunt trauma during the study period; 34.8% of the patients were men, 20.5% had at least one comorbidity, and 89.6% were white. Median LOS was 5 days; 37 (2.9%) patients died. Age of 85 and over (OR 3.44 with 95% CI 1.01−11.7 and 2.85 with 95% CI 1.0−6.76, when compared to 65−74 and 75−84, respectively), injury severity score (ISS) (OR 1.08, 95% CI 1.02 to 1.15) and the presence of more than one comorbidity (OR 2.68, 95% CI 1.26 to 5.68) were independently predictive of death on multi-variable logistic regression analysis. Conclusion: Age more than 85 years, higher injury severity score and the presence of more than one comorbidity are independent predictors of mortality among geriatric patients presenting with low-energy blunt trauma.

Weight Loss Outcomes following Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in an Ethnically Diverse Bariatric Population: Which Is More Effective?

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) have comparable weight loss outcomes in a general bariatric population. OBJECTIVES: This study aimed to investigate whether similar outcomes can be observed in Hispanic and African American population. Settings. Community Hospital in New York, New York, United States. METHODS: The 5-year prospective data of patients who underwent LRYGB and LSG at a single center were retrospectively reviewed. The long-term weight loss outcomes between patients who had LRYGB and LSG were compared after adjusting for age, sex, race, diabetes mellitus, and hypertension with the linear mixed-effects or logistic regression model. RESULTS: Most patients were Hispanic (59.2%) and African American (22.7%). The mean% total weight loss (%TWL) values of patients with BMI <45 kg/m2 who underwent LRYGB and LSG were 73% and 62% after 1 year, 69% and 56% after 2 years, and 71% and 54% after 5 years, respectively. In patients with a BMI of 45-50 kg/m2 who underwent LRYGB and LSG, the mean %TWL values were 69% and 56% after 1 year, 75% and 58% after 2 years, and 57% and 45% after 5 years, respectively. Meanwhile, the %TWL values of patients with BMI >50 kg/m2 who had LRYGB and LSG were 53% and 42% after 1 year, 53% and 45% after 2 years, and 49% and 36% after 5 years, respectively. All results were statistically significant (p < 0.0001) and remained valid after adjusting for cofactors. CONCLUSION: Thus, LRYGB had consistent and sustained long-term weight loss outcomes compared with LSG in a predominantly ethnically diverse patient population with different BMI. Our study had several limitations in that it is retrospective in nature and some patients were lost to follow-up during the study period.

Bariatric Surgery Improves Renal Function: a Large Inner-City Population Outcome Study.

BACKGROUND: Bariatric surgery is associated with improved renal dysfunction in general population studies. The study examined the effects of bariatric surgery on renal function in a predominantly Hispanic and African American population at a community hospital in New York, USA. METHODS: This retrospective study analyzed prospectively collected bariatric surgical data from 2247 patients (89% female) who underwent bariatric surgery at a single center. Changes in glomerular filtration rate (eGFR), urine albumin-creatinine ratio (UACR), micro- and macroalbuminuria, and hyperfiltration, which were measured preoperatively and then yearly for 3 years postoperatively, were evaluated with t tests and logistic regression analysis, after adjusting for confounding variables. The mean age of the patients at surgery was 37.1 years; the mean preoperative body mass index was 45 ± 7 kg/m2. RESULTS: The results obtained 3 years postoperatively showed the following significant improvements compared with the preoperative values: mean UACR decreased from 40.3 to 11.1 mg/g, mean eGFR improved from 79.4 to 87.3 mL/min, the prevalence of microalbuminuria decreased from 13.7 to 6.2%, the prevalence of macroalbuminuria decreased from 2.5 to 0%, and the prevalence of hyperfiltration decreased from 4.4 to 2.7% (all P < .0001). In adjusted multivariate regression analysis, these results remained significant after adjusting for age, sex, race, type of surgery, and presence of diabetes mellitus or hypertension. CONCLUSION: In this large study at an inner-city hospital, bariatric surgery was associated with significant improvements in renal dysfunction parameters. These results could assist with informed decisions regarding indications for bariatric surgery.

Improvement in glycated hemoglobin A1C after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy in an ethnically diverse population with diabetes.

BACKGROUND: Obesity is a well-known risk factor for the development of type 2 diabetes. The efficacy of bariatric surgery in reducing weight with resulting improvement in type 2 diabetes has been reliably demonstrated. OBJECTIVES: We investigated and compared the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) on glycated hemoglobin (HbA1C) levels in a predominantly Hispanic and black population. SETTINGS: Community Hospital in New York, New York, United States. METHODS: This is a retrospective review of a 5-year data from a single center where patients with diabetes who underwent LRYGB or LSG were included. HbA1C levels and body mass index were analyzed preoperatively and then annually postoperatively for up to 5 years. Improvements in HbA1C were compared between the 2 groups after adjusting for age, sex, race, and hypertension with linear mixed-effects or logistic regression models. RESULTS: Of the 676 included patients, 84.8% were females and the mean age was 47 years. HbA1C levels decreased significantly (P < .05) in the entire group at 1 (21%), 2 (20%), 3 (20%), 4 (18%), and 5 (14%) years. Compared with LSG, LRYGB patients displayed greater improvement in HbA1C levels at 1 year (25% versus 17%, P = .001). The differences in the reduction of HbA1C between LRYGB and LSG for the other time intervals were not significant (P > .05), 24% versus 17% (2 yr), 22% versus 16% (3 yr), 22% versus 13% (4 yr), and 17% versus 10% (5 yr). Changes in body mass index were not correlated to changes in HbA1C at various study points. CONCLUSION: Both LRYGB and LSG resulted in significant decreases in HbA1C levels and are correlated with changes in body mass index. LRYGB had the greatest effect at 1 year postoperatively. There was no significant difference in HbA1C reduction for LRYGB and LSG after 1 year postoperatively in this predominantly Hispanic and black cohort.

Phlegmonous Gastritis in a Bariatric Patient After Sleeve Gastrectomy.

Phlegmonous gastritis is a rare and progressive fatal condition that affects the mucosa and submucosa of the gastric wall. It can be localized or diffuse, affecting the entire stomach. It usually presents with upper gastrointestinal symptoms, such as nausea, vomiting, and hematemesis, along with systemic symptoms, including fever, chills, and fatigue. Risk factors include mucosal injury, surgery, hypoacidity, and immunosuppression that can be seen in human immunodeficiency virus (HIV)-positive or alcoholic patients. We present a case of phlegmonous gastritis which developed after a laparoscopic sleeve gastrectomy. The patient presented with epigastric pain, nausea, and chills two months post-sleeve gastrectomy. The diagnosis was made with computed tomography (CT) scan of the abdomen. She was managed successfully with CT-guided drainage and antibiotics.

Warfarin induced mesenteric and intestinal hematoma requiring surgical resection to relieve small bowel obstruction: A case report.

INTRODUCTION: Mesenteric and Intramural Hematoma leading to small bowel obstruction is a rare, but a fatal complication of anticoagulant therapy. PRESENTATION OF CASE: We present this unique case of 61 year old male with non traumatic mesenteric and intramural hematoma secondary to warfarin leading to small bowel obstruction requiring surgical resection. DISCUSSION: Although there have been few cases reported in literature about intramural small bowel hematoma, however, associated with small bowel obstruction secondary to warfarin therapy are less frequently seen. Diagnosis of intramural hematoma can be made with Computed Tomography (CT) of abdomen. The most effective treatment approach is conservative management after excluding any signs of small bowel obstructions, peritonitis and bowel necrosis. CONCLUSION: Therefore, early diagnosis is vitally essential to avoid morbidity in patients with these symptoms. Physician should have a higher index of suspicion to recognize and diagnose this complication is essential for early treatment intervention to prevent morbidity.

Paraplegia Following Spinal Cord Contusion from an Indirect Gunshot Injury.

Spinal cord injuries are debilitating and life threatening. Paraplegia due to direct traumatic gunshot injury to the spinal cord is common. The most common cause of spinal cord injury is road traffic accidents. This is followed by spinal cord injury due to a fall from a height. Most of the spinal cord injuries due to gunshot wounds occur as a result of direct traumatic effects. We present a rare case of a 49-year-old male with trauma. He developed paraplegia after a gunshot wound injury to the neck and contusion to the spinal cord, with no direct trauma. Paraplegia due to direct gunshot injury can have many different outcomes. In our case, the patient was managed conservatively, and the outcome was favorable.

Giant Mucinous Carcinoma of the Breast.

We report a case of giant mucinous carcinoma of the breast in a 55-year-old female who presented with left breast lump for two years. The patient did not seek any medical attention for two years. On exam, the lump measured 12 x 14 cm. Core needle biopsy showed invasive mucinous adenocarcinoma without ductal component. The patient underwent neo-adjuvant chemotherapy without any response. She underwent left modified radical mastectomy. All lymph nodes were negative. This was followed by adjuvant chemotherapy. Mucinous carcinoma is a rare type of breast cancer that carries a good prognosis compared to other types of breast cancers. In this report, we presented a giant mucinous carcinoma measuring 14 cm.

Tracheostomy Exchange Resulting in Rare Combination of Pneumomediastinum, Pneumothorax, Massive Pneumoperitoneum, and Subcutaneous Emphysema.

Tracheostomy tube change is a relatively common and simple procedure once a tract is formed between the skin and the trachea. Regular tracheostomy tube changes decrease the risk of postoperative pulmonary infection and granulation tissue formation. However, serious complications, such as loss of airway, subcutaneous emphysema, and mediastinitis, can occur if the tube exchange is performed inappropriately. We present a rare association of subcutaneous emphysema, tension pneumothorax, pneumomediastinum, and pneumoperitoneum following a tracheostomy tube exchange in a 56-year-old patient who had his tracheotomy placed a month ago. The patient was successfully managed conservatively by chest tube and supportive care.

Successful laparoscopic repair of gastro-gastric fistula following Roux-en-Y gastric bypass at Harlem Community Hospital.

Gastro-gastric fistula is a communication between the gastric remnant and gastric pouch. It is a rare complication of Roux-en-Y gastric bypass. It is caused by anastomotic leak, marginal ulcers, distal obstruction or erosion from foreign body. In this case report, we are presenting a successful laparoscopic repair of gastro-gastric fistula in a patient who presented with weight gain after initial loss.

A rare case of listeriosis, acute cholecystitis and multiple myeloma.

Listeria monocytogenes (LM) is an aerobic, motile, intracellular gram-positive bacterium. Most invasive systemic infections caused by LM are commonly seen in patients at both extremes of age, during pregnancy or in immunocompromised hosts. Common clinical manifestations of LM infection in immunocompromised adults are bacteremia, infections of central nervous system, such as meningitis, and self-limiting febrile gastroenteritis. Focal infections of listeria are rare, especially cholecystitis, with only few cases reported in the last 33 years. A 62-year-old man presented with multiple myeloma, cholecystitis and LM bacteremia. Due to prompt surgical treatment and antibiotics (amoxicillin plus clavulanic acid and gentamycin), this high-risk patient recovered without any complications.

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.

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.

Dectin-1 Regulates Hepatic Fibrosis and Hepatocarcinogenesis by Suppressing TLR4 Signaling Pathways.

Dectin-1 is a C-type lectin receptor critical in anti-fungal immunity, but Dectin-1 has not been linked to regulation of sterile inflammation or oncogenesis. We found that Dectin-1 expression is upregulated in hepatic fibrosis and liver cancer. However, Dectin-1 deletion exacerbates liver fibro-inflammatory disease and accelerates hepatocarcinogenesis. Mechanistically, we found that Dectin-1 protects against chronic liver disease by suppressing TLR4 signaling in hepatic inflammatory and stellate cells. Accordingly, Dectin-1(-/-) mice exhibited augmented cytokine production and reduced survival in lipopolysaccharide (LPS)-mediated sepsis, whereas Dectin-1 activation was protective. We showed that Dectin-1 inhibits TLR4 signaling by mitigating TLR4 and CD14 expression, which are regulated by Dectin-1-dependent macrophage colony stimulating factor (M-CSF) expression. Our study suggests that Dectin-1 is an attractive target for experimental therapeutics in hepatic fibrosis and neoplastic transformation. More broadly, our work deciphers critical cross-talk between pattern recognition receptors and implicates a role for Dectin-1 in suppression of sterile inflammation, inflammation-induced oncogenesis, and LPS-mediated sepsis.

TGF-ß Blockade Reduces Mortality and Metabolic Changes in a Validated Murine Model of Pancreatic Cancer Cachexia.

Cancer cachexia is a debilitating condition characterized by a combination of anorexia, muscle wasting, weight loss, and malnutrition. This condition affects an overwhelming majority of patients with pancreatic cancer and is a primary cause of cancer-related death. However, few, if any, effective therapies exist for both treatment and prevention of this syndrome. In order to develop novel therapeutic strategies for pancreatic cancer cachexia, appropriate animal models are necessary. In this study, we developed and validated a syngeneic, metastatic, murine model of pancreatic cancer cachexia. Using our model, we investigated the ability of transforming growth factor beta (TGF-ß) blockade to mitigate the metabolic changes associated with cachexia. We found that TGF-ß inhibition using the anti-TGF-ß antibody 1D11.16.8 significantly improved overall mortality, weight loss, fat mass, lean body mass, bone mineral density, and skeletal muscle proteolysis in mice harboring advanced pancreatic cancer. Other immunotherapeutic strategies we employed were not effective. Collectively, we validated a simplified but useful model of pancreatic cancer cachexia to investigate immunologic treatment strategies. In addition, we showed that TGF-ß inhibition can decrease the metabolic changes associated with cancer cachexia and improve overall survival.