Effect of combined tobacco use and type 2 diabetes mellitus on prevalent fibrosis in patients with MASLD.

BACKGROUND: Several studies have investigated the independent effect of cigarette smoking or type 2 diabetes mellitus (T2DM) on MASLD. However, the interaction effect between tobacco consumption and T2DM on MASLD severity remains underexplored. In this study, we assessed the combined effect of tobacco use and T2DM on hepatic fibrosis in MASLD. METHODS: We conducted a single-center retrospective cross-sectional analysis of eligible participants from the Mass General Brigham Fibroscan© database. The participants were divided into 3 groups: those with T2DM and a history of tobacco use (primary exposure group), those with T2DM but no history of tobacco use (secondary exposure group), and those without T2DM and no history of tobacco use (reference group). An additional model was developed, which included a fourth group, participants with a history of tobacco use but no T2DM. The likelihood of fibrosis was determined using a defined fibrosis-4 index cutoff value of 1.3. In addition, we computed the estimated marginal means for liver stiffness measurement and compared the values among the exposure groups. Bivariable and multivariable logistic regression models were used to explore the associations between the exposure groups and the risk for hepatic fibrosis. RESULTS: Overall, 598 individuals were enrolled in the study. The bivariable logistic regression model revealed a significant independent association between T2DM, combined smoking and T2DM, and the outcome of interest, fibrosis. Age, sex, metabolic syndrome, aspirin use, statin use, hemoglobin A1C (A1C), and total bilirubin level were also significantly associated with fibrosis. In the adjusted fibrosis-4 multivariable model (comparing exposure groups to controls), cigarette smoking and T2DM interaction had higher odds of prevalent fibrosis (aOR, 3.04; 95% CI, 1.62-5.76), compared to those with T2DM alone (aOR 2.28; 95% CI, 1.37-3.85). The continuous liver stiffness measurement comparison across the exposure group showed an estimated marginal means of 6.26 (95% CL: 5.58-6.94), 7.54 (95% CL: 6.78-8.30), and 7.88 (6.78-8.99) for the reference group, T2DM only group, and tobacco-T2DM group, respectively. The diabetes-only group and the combined tobacco-T2DM group had statistically significant associations with liver stiffness measurement (p values: 0.013 and 0.014, respectively). CONCLUSION: Although diabetes is independently associated with hepatic fibrosis in patients with MASLD, the combination of tobacco consumption and diabetes is associated with a higher prevalence of fibrosis. Therefore, lifestyle change through tobacco use cessation in patients with diabetes could be beneficial in reducing the incidence of liver fibrosis among individuals with MASLD.

Risk of Cardiovascular Disease in Individuals With Nonobese Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is independently associated with obesity and cardiovascular disease (CVD). CVD is the primary cause of mortality in the predominantly obese population of adults with NAFLD. NAFLD is increasingly seen in individuals who are lean and overweight (i.e., nonobese), but it is unclear whether their risk of CVD is comparable to those with NAFLD and obesity. Using a prospective cohort of patients with NAFLD, we compared the prevalence and incidence of CVD in individuals with and without obesity. NAFLD was diagnosed by biopsy or imaging after excluding other chronic liver disease etiologies. Logistic regression was used to compare the odds of baseline CVD by obesity status. Cox proportional hazards regression was used to evaluate obesity as a predictor of incident CVD and to identify predictors of CVD in subjects with and without obesity. At baseline, adults with obesity had a higher prevalence of CVD compared to those without obesity (12.0% vs. 5.0%, P = 0.02). During follow-up, however, obesity did not predict incident CVD (hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.69-2.22) or other metabolic diseases. Findings were consistent when considering body mass index as a continuous variable and after excluding subjects who were overweight. Age (adjusted HR [aHR], 1.05; 95% CI, 1.03-1.08), smoking (aHR, 4.61; 95% CI, 1.89-11.22), and decreased low-density lipoprotein levels (aHR, 0.98; 95% CI, 0.96-1.00) independently predicted incident CVD in the entire cohort, in subjects with obesity, and in those without obesity, respectively. Conclusion: Individuals with overweight or lean NAFLD are not protected from incident CVD compared to those with NAFLD and obesity, although CVD predictors appear to vary between these groups. Patients without obesity also should undergo rigorous risk stratification and treatment.

The assessment of sarcopenia using psoas muscle thickness per height is not predictive of post-operative complications in IBD.

BACKGROUND: Sarcopenia is associated with postoperative complications in inflammatory bowel disease. It has most commonly been defined using the skeletal muscle index, computed after analysis of cross-sectional muscle area at L3. Psoas muscle thickness normalized to height (PMTH), which is easier to derive, is a potential surrogate of SMI and sarcopenia in patients with cirrhosis and chronic pancreatitis. We investigate whether sarcopenia defined by PMTH has utility in predicting post-operative outcomes in patients with inflammatory bowel disease. METHODS: We performed a retrospective study of adults undergoing IBD-related surgery from 2009 to 2019 at two hospitals. Sarcopenia was defined by sex-specific PMTH at the umbilicus on cross-sectional imaging using a 50th percentile median cutoff. Predictive models were created using variables (BMI, age, sex, smoking status, albumin, INR, platelets, hemoglobin, hypertension, diabetes, CAD, medications) that may be associated with complications (mortality, reoperation, readmission, transfusions, ICU admission, infection, DVT/PE), and sarcopenia for comparison. RESULTS: 85 patients with IBD were included. Lower albumin level (OR = 0.52, p = 0.039) and biologic use (OR = 5.92, p = 0.006) were associated with postoperative complications. There was no significant difference using PMTH compared to a model incorporating hypoalbuminemia and biologic use in predicting complications. Sarcopenia on univariate analysis was associated with a lower 30 day rate of reoperation (p = 0.04). CONCLUSIONS: A low status of PMTH was not associated with increased postoperative complications, however hypoalbuminemia and biologic use were. PMTH as a surrogate for sarcopenia requires further study, ideally with prospective studies comparing PMTH with accepted radiographic surrogates for sarcopenia, to determine its role in clinical decision making.

Thiazolidinediones, alpha-glucosidase inhibitors, meglitinides, sulfonylureas, and hepatocellular carcinoma risk: A meta-analysis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide. Effects of second-line oral antidiabetic medications on incident HCC risk in individuals with type 2 diabetes mellitus remain unclear. This study evaluated associations between sulfonylureas, thiazolidinediones, meglitinides and alpha-glucosidase inhibitors, and incident HCC risk. METHODS: We systematically reviewed all studies on PubMed, Embase and Web of Science databases. Studies were included if they documented: (1) exposure to oral antidiabetic medication classes; (2) HCC incidence; (3) relative risks/odds ratios (OR) for HCC incidence. Eight eligible observational studies were identified. We performed random-effects meta-analyses to calculate pooled adjusted ORs (aORs) and 95% confidence intervals (CI). RESULTS: Thiazolidinedione use (7 studies, 280,567 participants, 19,242 HCC cases) was associated with reduced HCC risk (aOR = 0.92, 95% CI = 0.86-0.97, I2 = 43%), including among Asian subjects (aOR = 0.90, 95% CI = 0.83-0.97), but not Western subjects (aOR = 0.95, 95% CI = 0.87-1.04). Alpha-glucosidase inhibitor use (3 studies, 56,791 participants, 11,069 HCC cases) was associated with increased HCC incidence (aOR = 1.08; 95% CI = 1.02-1.14, I2 = 21%). Sulfonylurea use (8 studies, 281,180 participants, 19,466 HCC cases) was associated with increased HCC risk in studies including patients with established liver disease (aOR = 1.06, 95% CI = 1.02-1.11, I2 = 75%). Meglitinide use (4 studies, 58,237 participants, 11,310 HCC cases) was not associated with HCC incidence (aOR = 1.19; 95% CI = 0.89-1.60, I2 = 72%). CONCLUSIONS: Thiazolidinedione use was associated with reduced HCC incidence in Asian individuals with diabetes. Alpha-glucosidase inhibitor or sulfonylurea use was associated with modestly increased HCC risk; future research should determine whether those agents should be avoided in patients with chronic liver disease.

Aspirin Use Is Associated with a Reduced Incidence of Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

Hepatocellular carcinoma (HCC) is the third-leading cause of cancer-related death worldwide, with a growing incidence and poor prognosis. While some recent studies suggest an inverse association between aspirin use and reduced HCC incidence, other data are conflicting. To date, the precise magnitude of risk reduction-and whether there are dose-dependent and duration-dependent associations-remains unclear. To provide an updated and comprehensive assessment of the association between aspirin use and incident HCC risk, we conducted a systematic review and meta-analysis of all observational studies published through September 2020. Using random-effects meta-analysis, we calculated the pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between aspirin use and incident HCC risk. Where data were available, we evaluated HCC risk according to the defined daily dose of aspirin use. Among 2,389,019 participants, and 20,479 cases of incident HCC, aspirin use was associated with significantly lower HCC risk (adjusted RR, 0.61; 95% CI, 0.51-0.73; P ≤ 0.001; I2 = 90.4%). In subgroup analyses, the magnitude of benefit associated with aspirin was significantly stronger in studies that adjusted for concurrent statin and/or metformin use (RR, 0.45; 95% CI, 0.28-0.64) versus those that did not (P heterogeneity = 0.02), studies that accounted for cirrhosis (RR, 0.49; 95% CI, 0.45-0.52) versus those that did not (P heterogeneity = 0.02), and studies that confirmed HCC through imaging/biopsy (RR, 0.30; 95% CI, 0.15-0.58) compared with billing codes (P heterogeneity < 0.001). In four studies, each defined daily dose was associated with significantly lower HCC risk (RR, 0.98; 95% CI, 0.97-0.98), corresponding to an 8.4% risk reduction per year of aspirin use. Conclusion: In this comprehensive systematic review and meta-analysis, aspirin use was associated with a significant reduction in HCC risk. These benefits appeared to increase with increasing dose and duration of aspirin use.

Pituitary Apoplexy Case Series: Outcomes After Endoscopic Endonasal Transsphenoidal Surgery at a Single Tertiary Center.

BACKGROUND: The management of pituitary apoplexy, caused by acute hemorrhage and/or infarction of a pituitary adenoma, is debated. OBJECTIVE: To analyze clinical characteristics of patients undergoing endoscopic endonasal approaches (EEAs) for pituitary apoplexy. METHODS: A retrospective review of patients at our institution from 2012 to 2018 undergoing EEA for pituitary apoplexy diagnosed clinically and with imaging/pathologic findings. Analysis included demographics, symptoms, neuroendocrine deficits, neuroimaging, complications, symptom resolution, and follow-up details. RESULTS: Fifty patients (mean age, 53 years) were included. Preoperative symptoms included headache (86%), vision loss (62%), and cranial nerve paresis (40%). Mean tumor diameter was 2.7 cm and extrasellar extension was observed in 96% of tumors. Twenty-eight tumors were hemorrhagic (76%), 24 were necrotic (65%), and 13 (35%) had both features. Magnetic resonance imaging showed gross total resection in 58% of patients. Headache and vision loss improved in 87% and 86% of presenting patients. Cranial nerve paresis resolved in 72% of patients, partially improved in 11%, and remained unchanged in 17%. There were no deaths or carotid artery injuries. Surgical complications included postoperative cerebrospinal fluid leak (n = 4, 8%), epistaxis (n = 2, 4%), postoperative abscess (n = 1, 2%), and transient postoperative vision loss requiring reoperation (n = 1, 4%). Endocrinopathies improved in 21% of patients and panhypopituitarism persisted in 48% and developed in 6% of patients. Mean follow-up time was 26 months; 2 patients experienced recurrence. CONCLUSIONS: EEA for pituitary apoplexy is effective in rapidly improving headache and visual symptoms. Although neuro-ophthalmic deficits often improve over time, panhypopituitarism persists in most patients after surgical resection.

Culinary medicine and community partnership: hands-on culinary skills training to empower medical students to provide patient-centered nutrition education.

Given the economic burden and numerous morbidities associated with obesity and poor dietary choices, it is increasingly important for medical students to receive education on nutrition and preventive medicine so that they are equipped to advise patients about healthy lifestyle choices. Currently, 71% of US medical schools do not reach the minimum benchmark of 25 hours of nutrition education set by the National Academy of Sciences. In order to improve the quality and quantity of nutrition education at the Keck School of Medicine of USC (KSOM), medical students and faculty have partnered with LA Kitchen (LAK), a local teaching kitchen, and the Wellness Center at LA County Medical Center (LAC+USC). They developed a hands-on preclinical culinary and nutrition course that aims to teach students practical skills and knowledge that they will be able to apply to their own lives and pass onto patients. Following the completion of the first three years of the course (2016-2018), analysis suggests that the class was well-received and has improved students' nutrition knowledge, confidence in lifestyle counseling, and personal culinary skills. Given these highly encouraging observations, the project is currently aimed at incorporating nutrition education more broadly into the required preclinical curriculum at KSOM.

Outcomes Following Transsphenoidal Pituitary Surgery in the Elderly: A Retrospective Single-Center Review.

BACKGROUND: Transsphenoidal surgery (TSS) for pituitary adenomas (PAs) is performed on elderly patients with increasing frequency. More research is necessary to assess the risk factors that are associated with TSS in an aging population. OBJECTIVE: To perform a retrospective study on postoperative safety outcomes following TSS in the elderly population stratified by decade of life. METHODS: A retrospective chart review of the USC Pituitary Database was conducted to identify patients ≥70 yr, who underwent TSS for PAs between 1995 and 2017. Surgical outcomes were analyzed in elderly (≥70 yr) vs nonelderly (<70 yr) patients. Elderly patients were additionally stratified according to age 70 to 79 vs ≥80 yr. RESULTS: The cohorts included 115 elderly patients (70-79 yr: 94 patients; ≥80 yr: 21 patients) and 770 nonelderly patients. Elderly patients presented with more vision loss (62% vs 38%, P < .0001), dizziness (17% vs 6%, P = .0001) and altered mental status (7.3% vs 3%, P = .0451). Overall rates of surgical, medical, and endocrine complications were similar; however, elderly patients had significantly higher rates of postoperative hyponatremia (9.3% vs 4.7%, P = .0401) and lower rates of transient diabetes insipidus (0.9% vs 7.9%, P = .0038). Patients ≥ 80 yr had significantly more surgical complications (26.3%) compared to the 70 to 79 group (7.87%; P = .021) and <70 group (12.5%; P = .04). CONCLUSION: Patients >70 yr are appropriate surgical candidates for TSS given the similar safety outcomes as younger patients. Given the higher propensity for surgical complications; however, a higher level of operative selectivity should be maintained in octogenarian patients.

Variability and Lack of Prognostic Value Associated With Atypical Pituitary Adenoma Diagnosis: A Systematic Review and Critical Assessment of the Diagnostic Criteria.

BACKGROUND: Atypical pituitary adenomas (APAs) are a subset of pituitary adenomas (PAs) characterized by the 2004 World Health Organization (WHO) guidelines to have higher risk histopathological features than typical PAs. In July 2017, the WHO published an update to their classification of pituitary tumors and abandoned the APA terminology. OBJECTIVE: To assess the prevalence and outcomes of patients diagnosed with APA through a literature review. Focus was placed on variation in the application of the previous WHO criteria and on rates of recurrence. METHODS: A systematic review of PubMed (2004-July 2017) was performed to identify studies reporting prevalence and clinical characteristics/outcomes of APA. Eight studies were analyzed for prevalence. Six studies reporting histopathological details were analyzed in depth. RESULTS: Of the 7105 included patients, 373 (5.2%) met criteria for APA (prevalence range: 3%-15%). Only 2 of 8 studies utilized identical grading criteria, demonstrating a lack of standardized application. Most APAs (84%) were macroadenomas, with 52% invasive on magnetic resonance imaging. Nonfunctional PAs were most common (37%), followed by prolactinomas (23%) and Growth Hormone adenomas (21%). Recurrence/progression occurred in 21% of APA patients (follow-up range 37-75 mo). Only 2 of 8 studies reported an association between APA diagnosis and recurrence/progression. CONCLUSION: Based on diagnostic variability and lack of association with clinical outcomes, refinement of criteria for APA was necessary. The WHO update eliminates the ambiguity in APA diagnosis in favor of criteria that emphasize clinical behavior (invasion, recurrence, and resistance to treatment) and molecular markers. Our review supports abandonment of the previous APA designation due to limited prognostic utility.