Development of Clinical Algorithm Utilizing Vibration-Controlled Transient Elastography to Detect Advanced Hepatic Fibrosis in Liver Transplant Recipients.

INTRODUCTION: Vibration-controlled transient elastography (VCTE) based liver stiffness measurement (LSM) is an excellent 'rule-out' test for advanced hepatic fibrosis in liver transplant (LT) recipients, however, its ability to 'rule-in' the disease is suboptimal. The study aimed to improve diagnostic performance of LSM in LT recipients. METHODS: Adult LT recipients with a liver biopsy and VCTE were included (N = 150). Sequential covering analysis was performed to create rules to identify patients at low or high risk for advanced fibrosis (stage 3-4). RESULTS: Advanced hepatic fibrosis was excluded in patients with either LSM < 7.45 kPa (n = 72) or 7.45 ≤ LSM < 12.1 kPa and time from LT < 5.6 years (n = 25). Conversely, likelihood of advanced fibrosis was 95% if patients had LSM > 14.1 and controlled attenuation parameter > 279 dB/m (n = 21). Thus, 118 (79%) were correctly identified and 32 (21%) would have required a biopsy to establish the diagnosis. Compared to previously established LSM based cutoff values of 10.5 kPa (Youden index) and 13.3 kPa (maximized specificity), the false positive rates of sequential covering analysis was 1% compared to 16.5% with LSM ≥ 10.5 kPa and 8.3% with LSM ≥ 13.3 kPa. The true positive rates were comparable at 87% for sequential covering analysis, 93% for LSM ≥ 10.5 kPa and 83% for LSM ≥ 13.3 kPa. CONCLUSION: The proposed clinical sequential covering analysis allows for better risk stratification when evaluating for advanced fibrosis in LT recipients compared to LSM alone. Additional efforts are necessary to further reduce the number of patients with indeterminate results in whom a liver biopsy may be required.

Effectiveness of Tofacitinib in Ulcerative Proctitis Compared to Left Sided Colitis and Pancolitis.

BACKGROUND: Ulcerative proctitis (UP), though associated with high symptom burden and poor quality of life, is excluded from most of the randomized controlled trials in UC, including the OCTAVE trials. We aimed to analyse the effectiveness of tofacitinib in UP, and compare it to that in left sided colitis (LSC) and pancolitis (PC). METHODS: This was a prospective cohort study. Patients with either steroid-dependent or refractory ulcerative colitis, who received tofacitinib, were divided into three groups based on the disease extent [UP, LSC and PC]. The primary outcome was comparison of proportion of patients in clinical remission in the three groups, at weeks 8, 16 and 48. Safety outcomes were reported using incidence rate per patient year of exposure. RESULTS: Clinical remission was achieved in 47%(15/32), 24%(23/94), and 43%(23/54) of patients at week 8, 56%(18/32), 37%(35/94), and 56%(30/54) of patients at week 16, and 59%(19/32), 38%(36/94), and 24%(13/54) of patients at week 48 in groups UP, LSC and PC, respectively. Corticosteroid-free clinical remission rates were significantly higher in patients in groups UP at week 48. Five (15%) patients with UP were primary non-responders to tofacitinib at week 16, while three (9%) patients had secondary loss of response at week 48. The probability of sustained clinical response was highest in patients with UP. Patients with UP had the lowest incidence of adverse effects. CONCLUSION: The effectiveness of tofacitinib in inducing and maintaining clinical remission is greater in patients with UP compared to LSC and PC.

The cardio-oncology continuum: Bridging the gap between cancer and cardiovascular care.

Cancer and cardiovascular disease are two of the leading causes of death worldwide. Although cancer has historically been viewed as a condition characterized by abnormal cell growth and proliferation, it is now recognized that cancer can lead to a variety of cardiovascular diseases. This is due to the direct impact of cancer on the heart and blood vessels, which can cause myocarditis, pericarditis, and vasculitis. Additionally, cancer patients frequently experience systemic effects such as oxidative stress, inflammation, and metabolic dysregulation, which can contribute to the development of cardiovascular risk factors such as hypertension, dyslipidemia, and insulin resistance. It is important to closely monitor patients with cancer, especially those undergoing chemotherapy or radiation therapy, for cardiovascular risk factors and promptly address them. This article aims to explore the clinical implications of the underlying mechanisms connecting cancer and cardiovascular diseases. Our analysis highlights the need for improved cooperation between oncologists and cardiologists, and specialized treatment for cancer survivors.

Beyond Glycemic Control: Mechanistic Insights Into SGLT-2 Inhibitors in Heart Failure Management.

Heart failure is a common and clinically significant cardiac condition that causes significant morbidity and mortality in the United States. Diabetes and hypertension are 2 of the most common comorbidities associated with heart failure. Other risk factors for heart failure include smoking, obesity, and intrinsic cardiac diseases such as myocardial infarction and valvular pathologies. All of these conditions, to some extent, cause remodeling within the cardiomyocyte, which eventually leads to the development of congestive heart failure. Over the years, using diuretics and medications that inhibit the Renin-Angiotensin-Aldosterone System has been the traditional treatment for congestive heart failure. But in recent years studies in the diabetic population revealed that sodium-glucose cotransporter-2 inhibitors had a negative impact on the remodeling of cardiomyocytes. In this review, we discuss the numerous molecular mechanisms by which these recently developed medicines inhibit remodeling in cardiomyocytes, independent of their intended effect of decreasing blood glucose levels. Furthermore, it emphasizes the use of these drugs in diabetic as well as non-diabetic patients as a promising adjunct to ongoing heart failure treatment.

Understanding the Interplay between Iron Deficiency and Congestive Heart Failure: A comprehensive review.

Iron is an essential micronutrient for abounding physiological processes in the body, and its deficiency can be caused by various factors, such as low iron intake due to economic difficulties or loss of appetite, decreased iron absorption due to gastrointestinal issues, or increased iron loss due to hemorrhages or proteinuria. Iron deficiency is a prevalent issue among heart failure (HF) patients and is a significant contributor to anemia, affecting 30-50% of patients regardless of their gender, ethnicity, or left ventricular ejection fraction. Individuals with HF have high levels of pro-inflammatory cytokines, which can inhibit erythropoiesis by degrading the membrane iron exporter ferroportin, mediated by an increased release of hepcidin. In addition, elevated sympathetic and renin-angiotensin-aldosterone system activity retains salt and water, resulting in high cardiac output HF in people with normal left ventricular function. This review provides an overview of iron deficiency and HF.

Clinical and magnetic resonance imaging spectrum of complex perianal fistulizing Crohn's disease: A cohort study from northern India.

BACKGROUND: Fistulizing perianal Crohn's disease (CD) is a debilitating condition associated with significant morbidity and reduction in the quality of life. Magnetic resonance imaging (MRI) of the pelvis is the preferred imaging modality for the comprehensive assessment of the perianal fistula. There is a paucity of data from India on the MRI spectrum of complex perianal fistula in CD. METHODS: A single-centre cross-sectional analysis of patients with fistulizing perianal CD, who underwent pelvic MRI between January 2020 and December 2021, was performed. The clinical (age, sex, disease duration, disease location and behavior, disease activity [Perianal Disease Activity Index, PDAI] and treatment received) and radiological (number and location of fistulae, extensions, number and location of internal and external openings, fistula activity, presence or absence of perianal abscess and associated proctitis) characteristics of complex perianal fistula (defined according to the American Gastroenterological Association classification) were recorded. RESULTS: Of total 175 patients with CD who attended the gastroenterology clinic during the study period, 27 (15.42%) (mean age 42±15.5 years, 62.96% females and median disease duration four years) had complex perianal fistula and were included in the analysis. The mean PDAI was 5.48±2.53. The median Van Assche Index was 17 (interquartile range [IQR] 13-19). A majority (96.29%) of the fistulae were trans-sphincteric and four (14.81%) fistulae extended into the supralevator space. All fistulae were active on MRI. Concomitant perianal abscess and proctitis were seen in 59.26% (n=16) and 62.96% (n=17) of patients, respectively. Combination therapy with biologics and antibiotics/immune-suppressants were the most commonly prescribed medical therapy. Six (22.22%) patients underwent combined medical and surgical (non-cutting seton, fistulectomy, fecal diversion) treatment. CONCLUSION: The cumulative risk of the development of fistulizing perianal CD in a northern Indian cohort was similar to the western populations. Complex perianal fistulae were predominantly trans-sphincteric and commoner in females. MRI evaluation is pivotal for the delineation of fistula anatomy, assessment of disease extent and activity and the evaluation of concomitant perianal abscess and other complications.

Hydropneumothorax: A Presentation of Infected Bronchogenic Cyst.

Bronchogenic cysts are closed sac-like cystic lesions resulting from abnormal budding of the primitive foregut during the early development of the alimentary and respiratory systems. We describe the case of a 54-year-old man who presented to the emergency department with complaints of fever, chills, shortness of breath, and a productive cough with intermittent hemoptysis for the past two to three months. Initial workup revealed a right lung hydropneumothorax with complete atelectasis of the right lung and a mass effect on the left lung. During intercostal drainage, pleural fluid analysis revealed empyema with E. coli treated with antibiotics. However, the symptoms persisted after five days of antibiotic treatment and drainage. A multidisciplinary team of thoracic surgeons, anesthesiologists, and pulmonologists was assembled due to the non-resolving nature of the lung abscess. The patient underwent a right middle lobe lobectomy with decortication via open thoracotomy, and a bronchogenic cyst, an uncommon cause of the lung abscess, was suggested by histopathological analysis.

Prenatal predictors of need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida; systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate prenatal predictors of the need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida. DATA SOURCES: A systematic search was performed to identify relevant studies published from inception until June 2022 in the English language using the databases PubMed, Scopus, and Web of Science. STUDY ELIGIBILITY CRITERIA: We included retrospective and prospective cohort studies and randomized controlled trials reporting on prenatal repair of open spina bifida. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 9 studies including 948 pregnancies undergoing prenatal repair of open spina bifida were included in the final analysis. Prenatal factors that were significantly associated with the need for postnatal cerebrospinal fluid diversion were gestational age at surgery ≥25 weeks (odds ratio, 4.2; 95% confidence interval, 1.8-9.9; I2=54%; P=.001), myeloschisis (odds ratio, 2.2; 95% confidence interval, 1.1-4.1; I2=0.0%; P=.02), preoperative lateral ventricle width ≥15 mm (odds ratio, 4.5; 95% confidence interval, 2.9-6.9; I2=0.0%; P<.0001), predelivery lateral ventricle width (mm) (mean difference, 8.3; 95% confidence interval, 6.4-10.2; I2=0.0%; P<.0001), and preoperative lesion level at T12-L2 (odds ratio, 2.5; 95% confidence interval, 1.03-6.3; I2=68%; P=.04). Factors that significantly reduced the need for postnatal shunt placement were gestational age at surgery <25 weeks (odds ratio, 0.3; 95% confidence interval, 0.15-0.6; I2=67%; P=.001) and preoperative lateral ventricle width <15 mm (odds ratio, 0.3; 95% confidence interval, 0.2-0.4; I2=0.0%; P<.0001). CONCLUSION: This study demonstrated that among fetuses that underwent surgical repair of open spina bifida, having gestational age at surgery of ≥25 weeks, preoperative lateral ventricle width of ≥15 mm, myeloschisis lesion type, and preoperative lesion level above L3 was predictive of the need for cerebrospinal fluid diversion during the first year of life.

Is Coffee and Tea a Threat or Ally to Cardiovascular Health?

Tea and coffee have become ingrained in our daily lives and have become the most widely consumed drinks after water. Their effects vary on an individual basis depending upon the amount of daily consumption, genetic polymorphisms, and the presence of comorbidities. Non-habitual individuals experience an initial, brief increase in blood pressure due to caffeine's vasoactive effects. Caffeine also appears to be protective against arrhythmias and heart failure. Along with having a generally cardioprotective profile, they have also demonstrated to have a favorable impact on insulin resistance and reduced risk of diabetes mellitus. Physicians often practice caution and advise patients with known cardiovascular diseases to refrain from drinking caffeine; however, studies have shown that drinking two to three cups a day has either no or some beneficial effects on both patients with or without cardiac disorders like arrhythmias. This article focuses on the effects of tea and coffee on the cardiovascular system as well as the potential mechanisms involved.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

To Evaluate the Role of Positron Emission Tomography-Computerized Tomography in Initial Staging of Carcinoma Breast.

BACKGROUND: Breast cancer is the most common cancer in urban and second common in rural Indian women. In India, in spite of the best treatment available being given to the patients they lose their lives because of paucity of diagnostic aids and lack of an organized breast cancer screening program. Early detection, accurate staging, and initiation of appropriate therapy are the key factors for improving the treatment outcome and prognosis of the disease for the patients. Traditional staging methods include clinical examination, blood tests, chest X-ray, ultrasound of the abdomen, and/or skeletal survey. As these tests lack sensitivity and specificity, these are being scaled down. The hybrid positron emission tomography-computerized tomography (PET-CT) is a unique tool in the field of imaging modalities that combines the effectiveness of PET and CT. This study was undertaken to assess the efficacy and accuracy of PET-CT as a single-session staging modality in the very initial stage itself and if it can replace the conventional means of staging. METHODS: This was a cross-sectional study conducted in the Radiotherapy department at GGS Medical College and Hospital Faridkot from March 2014 to October 2015. 52 patients with newly diagnosed and histopathologically proven carcinoma breast were staged by conventional modalities (clinical examination, blood tests, X-ray chest, mammography, ultrasonography abdomen, skeletal survey) and by 18F-fluorodeoxyglucose (18F FDG) PET/CT. PET-CT images were used for the detection, localization, staging of tumors and detection, evaluation, and diagnosis of metastatic lesions, disease burden and organ function along with treatment planning and planning therapeutic procedures. Following the completion of initial study, the results of 18F FDG PET-CT staging in comparison with conventional staging method were assessed. Along with this, the accuracy, changes in staging of cases of carcinoma breast and cost-effectiveness of 18F-FDG PET-CT were also studied. RESULTS: All the pathologic entities identified by conventional imaging were also perceived with 18F-FDG PET/CT. Therefore, we recommend the use of PET/CT as an important imaging modality for initial diagnosis of carcinoma breast.

Redefining Role of 5-Fluorouracil and Exploring the Impact of Taxanes and Cisplatin in Locally Advanced and Recurrent Carcinoma Cervix in Concurrent Setting With Radiotherapy: A Literature Review.

Cervical carcinoma is the fourth most frequent cancer among women worldwide while it is common in rural India. The irony of the situation is that it continues to present in a locally advanced stage with bulky disease posing a significant challenge to the current treatment modalities despite various screening programs. Concurrent chemoradiotherapy is the mainstay of treatment for locally advanced carcinoma cervix. However, the appropriate dosing schedules, along with the salutation of the chemotherapeutic agent, remain a matter of debate to date. The use of chemotherapy in the neoadjuvant and adjuvant setting promises to improve progression-free survival and overall survival. The article aims to review various chemotherapy and their regimens in the treatment of carcinoma of the cervix.