Obesity is associated with poor surgical outcome in Crohn\u27s disease

BACKGROUND: Published data suggest a link between obesity and adverse outcomes in Crohn\u27s disease (CD). We aimed to test the hypothesis that obese CD patients would be more likely than non-obese CD patients to have poor surgical outcome when undergoing surgery for a complication of CD. METHODS: We designed a retrospective cohort study to test our hypothesis. The population comprised of adult CD patients who underwent CD related surgery at a tertiary referral center. The exposed and unexposed cohorts were represented by patients who were obese vs. non-obese at the pre-op visit respectively. Outcome was represented by successful vs. unsuccessful surgical outcome as deemed by the treating clinician. RESULTS: Ninety CD patients were eligible for inclusion into this cohort study of which 36 were obese (exposed cohort) and 54 were non-obese (unexposed cohort). Among obese CD patients, 64% had an unsuccessful surgical outcome vs. 41% with unsuccessful surgical outcome among the non-obese. Based on unadjusted bivariate analysis, potential confounders identified included age and type of surgery. Gender distribution, disease duration, ethnicity, tobacco use, steroid use, traditional and biological immune modulator use and clinical disease activity were similar between the two groups. Logistic regression adjusted for age and type of surgery revealed that obese CD patients were approximately 2.5 times more likely to have a poor surgical outcome than patients with CD who were not obese (P = 0.05 OR 2.53 95% CI 0.99 - 6.52). BMI as a continuous variable (adjusted for age and type of surgery) appeared to be associated with poor surgical outcome (P = 0.06 OR 1.07 95% CI 0.99 - 1.15). CONCLUSIONS: Obesity may be associated with poor surgical outcome in CD patients

Immune checkpoint inhibitor-induced subacute cutaneous lupus erythematosus: a case report and review of the literature

Immune checkpoint inhibitor (ICI) use has been associated with numerous autoimmune side effects, known as immune related adverse events (irAEs). Cutaneous irAEs are common and affect up to 50% of patients treated with ICIs. There have been an increasing number of cases reported in the literature regarding ICI-induced subacute cutaneous lupus erythematosus (SCLE). ICI-induced SCLE is important to recognize as it can result in a delayed and/or prolonged skin reaction despite treatment discontinuation. We describe a patient with gastro-esophageal adenocarcinoma who developed SCLE following one cycle of nivolumab treatment. A 75-year-old man presented to our clinic with a new photo-distributed rash composed of oval scaly pink papules and plaques involving his chest and arms. Despite treatment with topical corticosteroids, he presented to the emergency department 1 week later with worsening rash. Skin biopsy showed vacuolar interface pattern, along with superficial perivascular lymphocytic infiltrate, consistent with a drug eruption. The clinicopathological presentation was consistent with ICI-induced SCLE. Nivolumab treatment was discontinued due to the severity of the rash. The rash remitted with systemic corticosteroids, high potency topical steroids, and hydroxychloroquine. Unfortunately, the patient developed intraperitoneal metastatic disease, and was enrolled in hospice care. In this paper, we highlight the importance of early identification and treatment of this irAE. A review of the literature, including a discussion on the management of ICI-induced SCLE is also provided

Hypertension screening, awareness, treatment, and control in India:A nationally representative cross-sectional study among individuals aged 15 to 49 years

BACKGROUND: Evidence on where in the hypertension care process individuals are lost to care, and how this varies among states and population groups in a country as large as India, is essential for the design of targeted interventions and to monitor progress. Yet, to our knowledge, there has not yet been a nationally representative analysis of the proportion of adults who reach each step of the hypertension care process in India. This study aimed to determine (i) the proportion of adults with hypertension who have been screened, are aware of their diagnosis, take antihypertensive treatment, and have achieved control and (ii) the variation of these care indicators among states and sociodemographic groups. METHODS AND FINDINGS: We used data from a nationally representative household survey carried out from 20 January 2015 to 4 December 2016 among individuals aged 15-49 years in all states and union territories (hereafter "states") of the country. The stages of the care process-computed among those with hypertension at the time of the survey-were (i) having ever had one's blood pressure (BP) measured before the survey ("screened"), (ii) having been diagnosed ("aware"), (iii) currently taking BP-lowering medication ("treated"), and (iv) reporting being treated and not having a raised BP ("controlled"). We disaggregated these stages by state, rural-urban residence, sex, age group, body mass index, tobacco consumption, household wealth quintile, education, and marital status. In total, 731,864 participants were included in the analysis. Hypertension prevalence was 18.1% (95% CI 17.8%-18.4%). Among those with hypertension, 76.1% (95% CI 75.3%-76.8%) had ever received a BP measurement, 44.7% (95% CI 43.6%-45.8%) were aware of their diagnosis, 13.3% (95% CI 12.9%-13.8%) were treated, and 7.9% (95% CI 7.6%-8.3%) had achieved control. Male sex, rural location, lower household wealth, and not being married were associated with greater losses at each step of the care process. Between states, control among individuals with hypertension varied from 2.4% (95% CI 1.7%-3.3%) in Nagaland to 21.0% (95% CI 9.8%-39.6%) in Daman and Diu. At 38.0% (95% CI 36.3%-39.0%), 28.8% (95% CI 28.5%-29.2%), 28.4% (95% CI 27.7%-29.0%), and 28.4% (95% CI 27.8%-29.0%), respectively, Puducherry, Tamil Nadu, Sikkim, and Haryana had the highest proportion of all adults (irrespective of hypertension status) in the sampled age range who had hypertension but did not achieve control. The main limitation of this study is that its results cannot be generalized to adults aged 50 years and older-the population group in which hypertension is most common. CONCLUSIONS: Hypertension prevalence in India is high, but the proportion of adults with hypertension who are aware of their diagnosis, are treated, and achieve control is low. Even after adjusting for states' economic development, there is large variation among states in health system performance in the management of hypertension. Improvements in access to hypertension diagnosis and treatment are especially important among men, in rural areas, and in populations with lower household wealth

Variation in health system performance for managing diabetes among states in India:a cross-sectional study of individuals aged 15 to 49 years

Background: Understanding where adults with diabetes in India are lost in the diabetes care cascade is essential for the design of targeted health interventions and to monitor progress in health system performance for managing diabetes over time. This study aimed to determine (i) the proportion of adults with diabetes in India who have reached each step of the care cascade and (ii) the variation of these cascade indicators among states and socio-demographic groups. Methods: We used data from a population-based household survey carried out in 2015 and 2016 among women and men aged 15–49 years in all states of India. Diabetes was defined as a random blood glucose (RBG) ≥ 200 mg/dL or reporting to have diabetes. The care cascade—constructed among those with diabetes—consisted of the proportion who (i) reported having diabetes (“aware”), (ii) had sought treatment (“treated”), and (iii) had sought treatment and had a RBG < 200 mg/dL (“controlled”). The care cascade was disaggregated by state, rural-urban location, age, sex, household wealth quintile, education, and marital status. Results: This analysis included 729,829 participants. Among those with diabetes (19,453 participants), 52.5% (95% CI, 50.6–54.4%) were “aware”, 40.5% (95% CI, 38.6–42.3%) “treated”, and 24.8% (95% CI, 23.1–26.4%) “controlled”. Living in a rural area, male sex, less household wealth, and lower education were associated with worse care cascade indicators. Adults with untreated diabetes constituted the highest percentage of the adult population (irrespective of diabetes status) aged 15 to 49 years in Goa (4.2%; 95% CI, 3.2–5.2%) and Tamil Nadu (3.8%; 95% CI, 3.4–4.1%). The highest absolute number of adults with untreated diabetes lived in Tamil Nadu (1,670,035; 95% CI, 1,519,130–1,812,278) and Uttar Pradesh (1,506,638; 95% CI, 1,419,466–1,589,832). Conclusions: There are large losses to diabetes care at each step of the care cascade in India, with the greatest loss occurring at the awareness stage. While health system performance for managing diabetes varies greatly among India’s states, improvements are particularly needed for rural areas, those with less household wealth and education, and men. Although such improvements will likely have the greatest benefits for population health in Goa and Tamil Nadu, large states with a low diabetes prevalence but a high absolute number of adults with untreated diabetes, such as Uttar Pradesh, should not be neglected

Changing Landscape of Systemic Therapy in Biliary Tract Cancer

Biliary tract cancers (BTC) are often diagnosed at advanced stages and have a grave outcome due to limited systemic options. Gemcitabine and cisplatin combination (GC) has been the first-line standard for more than a decade. Second-line chemotherapy (CT) options are limited. Targeted therapy or TT (fibroblast growth factor 2 inhibitors or FGFR2, isocitrate dehydrogenase 1 or IDH-1, and neurotrophic tyrosine receptor kinase or NTRK gene fusions inhibitors) have had reasonable success, but <5% of total BTC patients are eligible for them. The use of immune checkpoint inhibitors (ICI) such as pembrolizumab is restricted to microsatellite instability high (MSI-H) patients in the first line. The success of the TOPAZ-1 trial (GC plus durvalumab) is promising, with numerous trials underway that might soon bring targeted therapy (pemigatinib and infrigatinib) and ICI combinations (with CT or TT in microsatellite stable cancers) in the first line. Newer targets and newer agents for established targets are being investigated, and this may change the BTC management landscape in the coming years from traditional CT to individualized therapy (TT) or ICI-centered combinations. The latter group may occupy major space in BTC management due to the paucity of targetable mutations and a greater toxicity profile

Selecting the first line treatment in non-metastatic hepatocellular carcinoma - comparing clinical practice guidelines

Primary malignancy of the liver or hepatocellular carcinoma (HCC) is unique in its presentation, disease process, and management. Unlike breast or colon cancer, the staging of HCC depends on performance status and baseline liver function along with pathological characteristics. Apart from traditional options like surgery and systemic therapy, effective management can be achieved in selected cases with liver transplant and locoregional therapy (LRT) like transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and ablation. Liver study societies and cancer groups across the globe proposed guidelines to aid the treating physicians in choosing first-line treatment for liver cancer. It is tough to compare these guidelines as they differ not only in treatment recommendations but also in risk assessment (and staging). The approach to the same patient may be different in the country he or she is managed. In clinical practice, decisions are usually taken on the consensus of multidisciplinary tumor boards and do not necessarily adhere to any guidelines. In the early (and very early) stage HCC, curative options like surgery, transplant, and ablation are recommended. In intermediate stage HCC, LRT (TACE and TARE) is preferred in the first line and systemic therapy for treatment failure or residual disease. Systemic therapy, including the atezolizumab/bevacizumab combination and tyrosine kinase inhibitors (TKI) like sorafenib and lenvatinib, is used for advanced stages. Supportive care is advised for terminal stage HCC

Is Cell-Free DNA Testing in Pancreatic Ductal Adenocarcinoma Ready for Prime Time?

Cell-free DNA (cfDNA) testing currently does not have a significant role in PDA management: it is insufficient to diagnose PDA, and its use is primarily restricted to identifying targetable mutations (if tissue is insufficient or unavailable). cfDNA testing has the potential to address critical needs in PDA management, such as pre-operative risk stratification (POR), prognostication, and predicting (and monitoring) treatment response. Prior studies have focused primarily on somatic mutations, specifically KRAS variants, and have shown limited success in addressing prognosis and POR. Recent studies have demonstrated the importance of other less prevalent mutations (ERBB2 and TP53), but no studies have provided reliable mutation panels for clinical use. Methylation aberrations in cfDNA (epigenetic markers) in PDA have been relatively less explored. However, early evidence has suggested they offer diagnostic and, to some extent, prognostic value. The inclusion of epigenetic markers of cfDNA adds another dimension to genomic testing and may open new therapeutic avenues beyond addressing critical areas of need in PDA treatment. For cfDNA to substantially influence PDA management, concerted efforts are required to include less frequent mutations and epigenetic markers. Furthermore, relying on KRAS mutations for PDA management will always be inadequate

Predictive Value of MUC5AC Signature in Pancreatic Ductal Adenocarcinoma: A Hypothesis Based on Preclinical Evidence

Mucin 5AC (MUC5AC) glycoprotein plays a crucial role in carcinogenesis and drug sensitivity in pancreatic ductal adenocarcinoma (PDAC), both individually and in combination with other mucins. Its function and localization are glycoform-specific. The immature isoform (detected by the CLH2 monoclonal antibody, or mab) is usually in the perinuclear (cytoplasmic) region, while the mature (45 M1, 2-11, Nd2) variants are in apical and extracellular regions. There is preclinical evidence suggesting that mature MUC5AC has prognostic and predictive (response to treatment) value. However, these findings were not validated in clinical studies. We propose a MUC5AC signature with three components of MUC5AC—localization, variant composition, and intensity—suggesting a reliable marker in combination of variants than with individual MUC5AC variants alone. We also postulate a theory to explain the occurrence of different MUC5AC variants in abnormal pancreatic lesions (benign, precancerous, and cancerous). We also analyzed the effect of mature MUC5AC on sensitivity to drugs often used in PDAC management, such as gemcitabine, 5-fluorouracil, oxaliplatin, irinotecan, cisplatin, and paclitaxel. We found preliminary evidence of its predictive value, but there is a need for large-scale studies to validate them

Is Cell-Free DNA Testing in Hepatocellular Carcinoma Ready for Prime Time?

Revamping the current biomarker landscape of hepatocellular carcinoma (HCC) with cell-free DNA (cfDNA) could improve overall outcomes. The use of commercially available cfDNA testing (also known as liquid biopsy) is limited by the low prevalence of targetable mutations and does not have any prognostic or predictive value. Thus, current cfDNA testing cannot be relied upon for perioperative risk stratification (POR), including early detection of recurrence, long-term surveillance, predicting outcomes, and treatment response. Prior evidence on cfDNA mutation profiling (non-specific detection or gene panel testing) suggests that it can be a reliable tool for POR and prognostication, but it still requires significant improvements. cfDNA methylation changes or epigenetic markers have not been explored extensively, but early studies have shown potential for it to be a prognostic biomarker tool. The predictive value of cfDNA (mutations and EM) to assist treatment selection (systemic therapy, immune-checkpoint inhibitor vs. tyrosine kinase inhibitor) and to monitor response to systemic and locoregional therapies should be a future area of focus. We highlighted the unmet needs in the HCC management and the current role of cfDNA testing in HCC in addressing them

Understanding the Clinical Significance of MUC5AC in Biliary Tract Cancers

Biliary tract cancers (BTC) arise from biliary epithelium and include cholangiocarcinomas or CCA (including intrahepatic (ICC) and extrahepatic (ECC)) and gallbladder cancers (GBC). They often have poor outcomes owing to limited treatment options, advanced presentations, frequent recurrence, and poor response to available systemic therapy. Mucin 5AC (MUC5AC) is rarely expressed in normal biliary epithelium, but can be upregulated in tissues of benign biliary disease, premalignant conditions (e.g., biliary intraepithelial neoplasia), and BTCs. This mucin’s numerous glycoforms can be divided into less-glycosylated immature and heavily-glycosylated mature forms. Reported MUC5AC tissue expression in BTC varies widely, with some associations based on cancer location (e.g., perihilar vs. peripheral ICC). Study methods were variable regarding cancer subtypes, expression positivity thresholds, and MUC5AC glycoforms. MUC5AC can be detected in serum of BTC patients at high concentrations. The hesitancy in developing MUC5AC into a clinically useful biomarker in BTC management is due to variable evidence on the diagnostic and prognostic value. Concrete conclusions on tissue MUC5AC are difficult, but serum detection might be relevant for diagnosis and is associated with poor prognosis. Future studies are needed to further the understanding of the potential clinical value of MUC5AC in BTC, especially regarding predictive and therapeutic value