Human Neutrophil α-Defensins 1-3 Are Upregulated in the Microenvironment of Fibrotic Liver.

Background and Objectives: Neutrophil infiltration is an established signature of Non-Alcoholic Fatty Liver Disease (NAFLD) and Steatohepatitis (NASH). The most abundant neutrophilic peptide, alpha-defensin, is considered a new evolving risk factor in the inflammatory milieu, intimately involved in lipid mobilization. Our objective is to assess for potential association between alpha-defensin immunostains and NAFLD severity. Materials and Methods: We retrospectively investigated the liver biopsies of NAFLD/NASH patients, obtained at Hillel Yaffe Medical center between the years 2012 and 2016. Patients' characteristics were recorded, including relevant blood tests at the time of biopsy. Each biopsy was semi-quantitatively scored using NAFLD Activity Score (NAS) and NASH fibrosis stage. The biopsies were immunostained for alpha-defensin. The precipitation of alpha-defensin was correlated to NAS and fibrosis. Results: A total of 80 biopsies were evaluated: male ratio 53.2%, mean age 44.9 ± 13.2 years, 54 had fibrosis grades 0-2, and 26 were grade 3-4. Conventional metabolic risk factors were more frequent in the high-grade fibrosis group. Immunostaining for alpha-defensin disclosed higher intensity (a.u.) in grade 3-4 fibrosis relative to grades 0-2, 25% vs. 6.5%, p < 0.05, respectively. Moreover, alpha-defensin staining was nicely co-localized with fibrosis. Conclusions: In our group of NASH/NAFLD patients, higher metabolic risk profile was associated with higher fibrosis grade. Immunostaining for alpha-defensin showed patchy intense staining concordant with high fibrosis, nicely co-localized with histological fibrosis. Whether alpha-defensin is a profibrotic risk factor or merely risk marker for fibrosis must be clarified in future studies.

Ethnic disparities in colorectal cancer outcomes: a population study from Israel.

Objectives: Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide. Clear ethnic disparities in the incidence of CRC and its outcomes have been observed globally, but only few research efforts have been invested so far in the unique ethnic scene of Israeli population. This study aims to compare the clinico-pathologic features, tumor's characteristics and prognosis between Arab and Jewish CRC patients as well as among Jewish subgroups living within the same central coastal region in Israel.Methods: In this retrospective, single center study, a total of 401 patients with pathologically confirmed CRCs diagnosed during the years 2008-2015 were included. These were divided into Jewish (n = 334) and Arab (n = 67) groups. Data collected included demographics, country of birth, clinical presentation and family history. Tumor stage, location, histologic grade and mortality rate were compared retrospectively between both groups and within Jewish sub-populations.Results: Arabs were significantly younger at diagnosis (62.7 ± 12.9 vs. 69.3 ± 13.01; P < 0.01), presented more frequently with rectal bleeding, and were less likely to be diagnosed due to positive fecal occult blood test (9% vs. 22.6%; P = 0.012). Tumor distribution through the colon was comparable between both groups and characterized by a distal predominance. Arabs had a significantly higher rate of advanced stage at diagnosis (58% vs. 50.5%, OR = 2.454, 95%CI = 1.201-5.013; P = 0.02) when compared to Jews. Mortality rates were comparable between both groups. In the Jewish subpopulation analysis, we found that immigrants, especially those born in the former USSR, presented with significantly advanced tumor stages when compared to native Israelis (55% vs. 37.5%; P = 0.02).Conclusion: CRC in two major ethnic populations in Israel, Arabs and Jews, varied in terms of age at diagnosis, clinical presentation and stage at diagnosis. Similar findings were documented within a non-native Jewish subpopulation, raising the possibility of a low utilization of screening programs in these groups.

Predictors of Clinical Course and Outcomes of Acute Diverticulitis: The Role of Age and Ethnicity.

Background and Objectives: Acute diverticulitis (AD) is the leading and most burdensome complication of colonic diverticulosis. However, risk factors for its development and predictors of its course are still poorly defined. In this regard, the association of a young age with a complicated course and worse outcome are still controversial. Moreover, little research has addressed the effect of ethnicity on the course of AD. The current study aimed to evaluate the impact of these variables on AD's course and outcome in the diverse and unique ethnic landscape of Israel. Materials and Methods: We performed a retrospective review of the charts of patients with a radiologically confirmed diagnosis of AD. Patients' outcomes and disease course, including hospitalization duration, complications, and recurrent episodes, were documented and compared among different age and ethnic groups. Multivariate analysis was performed to identify predictors of complicated AD. Results: Overall, 637 patients with AD were included, the majority (95%) had distal colon AD, and almost one quarter of them were aged less than 50 years. The majority of patients in the young age (<50) group were males (69.7%). Nonetheless, the rate of recurrent episodes (35.3% vs. 37.3%, p = 0.19), hospitalization duration (5 ± 4.7 vs. 6 ± 3.2, p = 0.09) and complications rate (17.3% vs. 13.7%; p = 0.16) were similar for both age groups. In the ethnicity group analysis, Arab minority patients had a first episode of AD at a significantly younger age compared to their Jewish counterparts (51.8 vs. 59.4 years, p < 0.001). However, factors such as a complicated course (16% vs. 15%; p = 0.08) and relapsing episode rates (33% vs. 38%; p = 0.36) did not differ significantly between groups. None of the variables, including young age and ethnic group, were predictors of complicated AD course in the multivariate analysis. Conclusion: AD is increasingly encountered in young patients, especially in ethnic minority groups, but neither ethnicity nor young age was associated with worse outcomes.

The Yield of Colonoscopy in the Evaluation of Constipation: An Age-Based Analysis of Outcome.

Background: Chronic constipation, a prevalent gastrointestinal complaint, exhibits rising incidence and diverse clinical implications, especially among the aging population. This study aims to assess colonoscopy performance in chronic constipation across age groups, comprehensively evaluating diagnostic yield and comparing results with average-risk controls. Methods: A retrospective analysis was conducted on 50,578 colonoscopy procedures performed over 12 years, including 5478 constipated patients. An average-risk control group (n = 4100) was included. Data extracted from electronic medical records covered demographics, operational aspects, and colonoscopy findings. The primary outcome measures included the diagnosis rate of colorectal cancer (CRC), polyp detection rate (PDR), and inflammatory bowel disease (IBD) diagnoses in constipated patients versus controls, with age-based and multivariate analyses. Results: Constipated patients exhibiting lower rates of adequate bowel preparation (92.7% vs. 85.3%; p < 0.001) and a lower cecal intubation rate. No significant variances between CRC and PDR were observed between constipated and controls, except for a potential of a slightly elevated CRC risk in constipated patients older than 80 (2.50% vs. 0% in controls; p = 0.07). Multivariate analysis demonstrated, across all age groups, that constipation did not confer an increased risk for CRC or polyp detection. Younger constipated patients exhibited a higher rate of IBD diagnoses (1.7% vs. 0.1% in controls; p < 0.001). Conclusions: Constipation did not confer an increased risk for CRC or polyps, among any age groups, except for a potential signal of elevated CRC risk in patients older than 80; additionally, it was associated with higher rates of IBD in younger patients.

Hepatitis B virus infection and risk of colorectal cancer: a large, population-based cohort study from Israel.

BACKGROUND: Recent population-based studies have suggested a possible link between hepatitis B (HBV) infection and extra-hepatic malignancies. We aimed to evaluate the association between HBV and colorectal cancer (CRC) using a large, population-based cohort study utilizing data from a large health maintenance organization (HMO). METHODS: The study included patients with non-cirrhotic HBV based on relevant ICD-9-CM codes and supportive serology identified from the HMO's database. Age-, sex-, ethnicity-, and BMI-matched non-HBV patients in a 1:10 ratio were included in the control group. We assessed the overall diagnosis rate of CRC and hepatocellular carcinoma (HCC) during the study period and calculated the diagnosis rate of CRC in each age category (≤50, 51-70, and ≥70) in both groups. RESULTS: A total of 3430 HBV patients and 34,300 controls were included in the study. The mean age, sex, BMI, and ethnic composition were similar, and the rates of family history of CRC did not differ between both groups. The overall follow-up period was 134±16 months. The diagnosis rate of HCC (1.6% vs. 0.1%; P<0.0001) was significantly higher in the HBV patients. However, the proportion of CRC was comparable for both groups (0.6% vs. 0.8%, P=0.404), which was evident in all age subgroups. CONCLUSIONS: Our findings suggest that HBV infection is associated with an increased risk of HCC diagnosis but is not linked to an elevated risk of CRC. These findings may inform future clinical practice and research regarding the relationship between HBV and extrahepatic malignancies.

Chronic hepatitis B infection and diabetes mellitus: a double liver trouble?

BACKGROUND: Concomitant Diabetes mellitus (DM) is commonly recognized in patients with chronic hepatitis B (CHB) infection, although its impact on liver-related outcomes remains controversial. We aimed to evaluate the effect of DM on the course, management and outcome of patients with CHB. METHODS: We performed a large retrospective cohort study utilizing the Leumit-Health-Service (LHS) database. We reviewed electronic reports of 692106 LHS members from different ethnicities and districts in Israel from 2000-2019 and included patients with CHB diagnosis based on ICD-9-CM codes and supportive serology results. These were divided into two cohorts of patients with CHB and DM (CHD-DM) (N.=252) and those with CHB without DM (N.=964). Clinical parameters, treatment figures and patients' outcomes were compared and multiple regression models and Cox regression analysis were performed to investigate the association between DM and cirrhosis/HCC risk in CHB patients. RESULTS: CHD-DM patients were significantly older (49.2±10.9 vs. 37.9±14, P<0.001), and had higher rates of obesity (BMI>30) and NAFLD (47.2% vs. 23.1%, and 27% vs. 12.6%, P<0.001, respectively). Both groups had a predominance of inactive carrier (HBeAg negative infection) state, but the HBeAg seroconversion rate was significantly lower in the CHB-DM group (25% vs. 45.7%; P<0.01). Multivariable Cox regression analysis showed that DM was independently associated with increased cirrhosis risk (HR 2.63; P=0.002). Older age, advanced fibrosis and DM were associated with HCC, but DM did not reach significance (HR 1.4; P=0.12) possibly due to the small number of HCC cases. CONCLUSIONS: Concomitant DM in CHB patients was significantly and independently associated with cirrhosis and possibly with increased risk of HCC.

Clinical and endoscopic predictors of gastric precancerous conditions: a large population case control study.

BACKGROUND: Atrophic gastritis (AG) and gastric intestinal metaplasia (GIM) are well defined intermediate precancerous conditions (PCCs) in the gastric cancer cascade. The diagnosis of PCCs may be suspected based on endoscopic findings but is established by histology. Estimates of the global prevalence of PCCs vary widely but simple clinical or endoscopic predictors of their diagnosis are ill defined. We aimed to evaluate the prevalence of gastric PCCs in our practice and to identify predictors for its diagnosis. METHODS: We analyzed electronic reports of patients referred for gastroscopy procedures over a 5-year period and included those for whom gastric biopsies were performed. We investigated demographic, clinical, and endoscopic findings to identify possible association with histologic detection of gastric PCCs and performed multivariate analysis to identify predictors of its diagnosis. RESULTS: A total of 4930 patients with full endoscopic and histologic data were included for the final analysis. Of these, 806 (16.3%) patients had a histologic diagnosis of gastric PCCs. Demographic and clinical variables including male sex (51.4% vs. 45.7%; P=0.003), age over 60 (69.8% vs. 45.2%; P<0.001), and anemia indication for gastroscopy (17.6% vs. 14.8%; P=0.04) were significantly associated with gastric PCCs diagnosis. Likewise, endoscopic findings of Barret's esophagus (2.6% vs. 1.3%; P=0.006), atrophic gastritis according to endoscopist's judgment (12.9% vs. 3.5%; P<0.01) and corpus predominant gastritis (22.5% vs. 14.7%; P=0.02) were significantly associated with gastric PCCs. In multivariate analysis, age>60 (please explain all acronyms HR 2.51, 95% CI 2.12-2.96), male sex (HR 1.235, 95% CI 1.05-1.44), corpus predominant (HR 1.284, 95% CI 1.04-1.57), and atrophic gastritis (HR 4, 95% CI 3.07-5.21) were independent predictors for PCCs diagnosis. CONCLUSIONS: Not uncommonly encountered in our practice, a judicious performance of gastric biopsies to detect gastric PCCs should be adopted especially in older, male patients with endoscopic findings of corpus predominant and/or gastric atrophy.

Pulmonary embolism risk in hospitalized patients with nonalcoholic fatty liver disease: A case-control study.

Abundant research has associated nonalcoholic fatty liver disease (NAFLD) with atherosclerosis, but very few reports have evaluated the association between NAFLD and venous thromboembolism. We aimed to investigate the association between NAFLD and pulmonary embolism (PE) in hospitalized patients. In this retrospective case-control study, we included consecutive patients from 2 university-affiliated hospitals who were referred for CT pulmonary angiograms for a suspected PE. Patients with a history of excessive alcohol consumption, chronic liver diseases or cirrhosis were excluded. The imaging studies of the entire cohort were reviewed by 2 expert radiologists who confirmed the diagnosis of PE and examined the liver to detect and grade hepatic steatosis. Accordingly, patients were categorized into NAFLD patients and non-NAFLD controls. Patient demographics, medical history, hospitalization details as well as patients' outcomes were documented. Multivariate analysis was performed to identify predictors for developing PE and hazard ratios with corresponding 95% confidence intervals were estimated. A total of 377 patients (101 with NAFLD and 276 controls) were included. NAFLD patients had significantly higher BMI values (33.16 ±â€…6.78 vs 26.81 ±â€…5.6; P < .001) and prevalence of diabetes (41 (40%) vs 85 (30.8%); P = .03). The prevalence of PE was significantly higher in the NAFLD group (80 (79.2%) vs 147 (53.3%), P < .001). In a multivariate analysis, older age, recent surgery or trauma, active malignancy, smoking, and NAFLD (HR ratio = 4.339, P < .0001 and 95% CI = 2.196-8.572) were independently associated with PE development. Patients with NAFLD were associated with an increased risk of developing PE independent of other classical risk factors for PE.

Acute complicated diverticulitis is associated with an increased advanced neoplasia diagnosis rate: A retrospective study on 1852 patients.

ABSTRACT: Recent reports have documented an unchanged rate of occurrence of colorectal cancer (CRC) and have publicised doubts regarding the benefit of prompt colonoscopy procedures after an episode of acute diverticulitis (AD). These reports mandate further evaluation of colonoscopy yield and timing in this regard. The current study aims to determine whether the rate of advanced colonic neoplasia after AD differs from that of average-risk patients, and to identify risk factors that are associated with their development.In this retrospective study, we included all patients who had been hospitalized to the surgery ward in the years 2008 to 2016 with radiographically confirmed AD, and had completed colonoscopies within one year of index hospitalization. Patients who were referred for screening colonoscopies during the same years were included as a control group. We compared the rates of diagnosis of CRC and advanced polyps for both groups before and after adjustment for multiple confounders. Moreover, we investigated risk factors that were associated with increased rate of advanced neoplasia diagnosis.A total of 350 patients were included in the AD group and 1502 patients in the screening colonoscopy control group. The CRC diagnosis rates (1.7% vs 0.3%; P = .09) and overall diagnosis rates of advanced neoplasia (12.3% vs 9.6%; P = .19) were not significantly different when findings were compared between the AD and control groups, respectively. Cases of complicated diverticulitis, however, were associated with increased risk of advanced neoplasia diagnosis (odds ratio (OR) 3.729, 95% confidence interval (CI) 1.803-7.713; P = .01).The diagnosis rate for advanced neoplasia after AD was not significantly different from that of average-risk populations. A course of complicated AD, however, was a potential risk factor.

Obstructive colon cancers at endoscopy are associated with advanced tumor stage and poor patient outcome. A retrospective study on 398 patients.

BACKGROUND: The detection of obstructive colorectal cancer (CRC) masses during endoscopic examination hindering the passage of endoscope and precluding complete examination is not uncommon. The significance and implications of this finding on patients' prognosis and outcomes were not fully investigated and will be addressed in this study. METHODS: In this retrospective cohort study, we reviewed endoscopy, surgery, pathology and oncology reports of patients diagnosed with CRC over a 10-year period (2007-2016). We compared surgical stages, histologic grades and overall survival between patients with subclinical obstructive tumors at endoscopy to those with nonobstructive tumors. We performed multivariate analysis to identify independent risk factors associated with advanced CRC stage at diagnosis. RESULTS: A total of 144 patients had obstructive colonic tumors while 254 had nonobstructive tumors and constituted the control group. Obstructive CRC group was significantly associated with advanced tumor stage at diagnosis (69 vs. 42%, OR = 3.018, 95% CI, 1.951-4.670; P < 0.01) and had prominently higher rates of moderate to poorly differentiated tumors (64.5 vs. 38.4%; P < 0.001) when compared to non-obstructive controls. Patients with obstructive tumors were significantly associated with decreased five years overall survival (53.4 vs. 67.3% vs.; P < 0.01). Increased overall mortality was observed in survival curves of patients with obstructive tumors along all follow-up periods. CONCLUSION: Even in the absence of clinical sequela, obstructive CRC at endoscopic level may be associated with higher stage at diagnosis and reduced overall survival. Further prospective studies are warranted to confirm these findings and address their implication on patients' management.

A rare case of adult colocolonic intussusception of the descending colon.

A 28-year-old woman approached the emergency department because of recent diffuse abdominal pain and diarrhoea. Peritoneal signs on physical exam led to abdominal CT scan which demonstrated colonic obstruction, resulting from colocolonic intussusception of the descending colon. An exploratory laparotomy confirmed the diagnosis as well as the aetiology of a 4 cm intraluminal polyp. Left hemicolectomy with primary anastomosis was performed. The final pathology revealed a tubulovillous adenoma with multiple foci of high-grade dysplasia. Intussusception is a rare cause for colonic obstruction, and ~90% of cases in adults are secondary to an anatomical or pathological condition. Therefore, we recommend oncological resection of the affected part.