A Systematic Critical Review of Clinical Pharmacokinetics of Torasemide.

PURPOSE: Torasemide is a potassium-sparing loop diuretic used to treat fluid retention associated with congestive heart failure and kidney and hepatic diseases. This systematic review was conducted to combine all accessible data on the pharmacokinetics (PK) of torasemide in healthy and diseased populations, which may help clinicians avert adverse drug reactions and determine the correct dosage regimen. METHODS: Four databases were systematically searched to screen for studies associated with the PK of torasemide, and 21 studies met the eligibility criteria. The review protocol was registered in the PROSPERO database (CRD42023390178). RESULTS: A decrease in maximum plasma concentration (C max ) was observed for torasemide after administration of the prolonged-release formulation in comparison to that after administration of the immediate-release formulation, that is, 1.12 ± 0.17 versus 1.6 ± 0.2 mcg/mL. After administering an oral dose of torasemide, a 2-fold increase in the area under the concentration-time curve (AUC) was reported in patients with congestive heart failure compared with the healthy population. Moreover, the patients with renal failure (clearance < 30 mL/min) showed an increase in value of AUC 0-∞ that is, 42.9 versus 8.091 mcg.h -1 .mL -1 compared with healthy subjects. In addition, some studies have reported interactions with different drugs, in which irbesartan showed a slight increase in the AUC 0-∞ of torasemide, whereas losartan and empagliflozin did not. CONCLUSIONS: The current review summarizes all available PK parameters of torasemide that may be beneficial for avoiding drug-drug interactions in subjects with renal and hepatic dysfunction and for predicting doses in patients with different diseases.

Structural insights into the mechanism of resistance to bicalutamide by the clinical mutations in androgen receptor in chemo-treatment resistant prostate cancer.

Despite advanced diagnosis and detection technologies, prostate cancer (PCa) is the most prevalent neoplasms in males. Dysregulation of the androgen receptor (AR) is centrally involved in the tumorigenesis of PCa cells. Acquisition of drug resistance due to modifications in AR leads to therapeutic failure and relapse in PCa. An overhaul of comprehensive catalogues of cancer-causing mutations and their juxta positioning on 3D protein can help in guiding the exploration of small drug molecules. Among several well-studied PCa-specific mutations, T877A, T877S and H874Y are the most common substitutions in the ligand-binding domain (LBD) of the AR. In this study, we combined structure as well as dynamics-based in silico approaches to infer the mechanistic effect of amino acid substitutions on the structural stability of LBD. Molecular dynamics simulations allowed us to unveil a possible drug resistance mechanism that acts through structural alteration and changes in the molecular motions of LBD. Our findings suggest that the resistance to bicalutamide is partially due to increased flexibility in the H12 helix, which disturbs the compactness, thereby reducing the affinity for bicalutamide. In conclusion, the current study helps in understanding the structural changes caused by mutations and could assist in the drug development process.Communicated by Ramaswamy H. Sarma.

Clinical pharmacokinetics of nebivolol: a systematic review.

Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC0-∞) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (Cmax) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC0-∞ of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher Cmax, AUC0-∞ and half-life (t1/2) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.

Classification of Chemotherapy-Induced Febrile Neutropenic Episodes Into One of the Three Febrile Neutropenic Syndromes.

Introduction Febrile neutropenia is a commonly encountered medical emergency in patients undergoing cancer treatment and can delay and modify the course of treatment and even lead to dire outcomes, including death. The cause of fever in a post-chemotherapy-induced neutropenic patient can be confusing to treating physicians. A review of the literature demonstrated that blood culture results could determine the cause of febrile neutropenia in only approximately 10% to 25% of patients. The objective of our study was to measure the incidence of positive blood cultures, urine cultures, and other body fluid cultures resulting in chemotherapy-induced neutropenia and further classify fever episodes into three neutropenic fever syndromes, such as microbiologically documented, clinically suspected, or unknown causes of fever, respectively. Methods We conducted a prospective observational study on 399 chemotherapy-induced neutropenic fever episodes with the aim of classifying them into one of the three neutropenic syndromes. We tried to document the cause of the fever in these patients. We also noted the type of cancer treatment regimen they were on and correlated their clinical profile with their body fluid cultures, including blood cultures, urine cultures, and other body fluid cultures. We then categorized each fever episode into one of three neutropenic syndromes. Results We studied 399 febrile neutropenic episodes. We were able to microbiologically document the cause of fever in 39% of the cases, and we obtained growth in 51 out of 399 blood cultures (13%), which was comparable to the available literature, and urine culture showed growth in 62 out of 399 cultures (16%), while other body cultures such as pus culture, bile culture, and bronchioalveolar lavage cultures collectively showed growth in 42 out of 399 episodes (10%). The most common bacteria isolated in both blood and urine cultures were Escherichia coli. Cumulatively, including blood, urine, and body fluid cultures, we were able to classify 39% (155 out of 399 cases) of febrile neutropenic episodes as microbiologically documented. The cause of fever was clinically suspected by means of careful history taking and an extensive physical examination in 31% (125 out of 399) without growth evidence in blood cultures, urine cultures, or any other body fluid culture. The cause of fever remained unknown in 119 cases (30%) of patients and was classified under the unknown cause of fever. Conclusions We conclude by stating that the study of fever in a neutropenic patient should include a thorough history and clinical evaluation of blood, urine, and other body fluid cultures instead of solely relying on blood culture results. We recommend further classifying patients into one of the three neutropenic fever syndromes, such as those that are microbiologically documented, clinically suspected, or unknown. Our blood cultures were able to give us a 13% positivity rate, whereas microbiologically, we were able to isolate an organism likely causing fever in 39% of patients. The cause of fever was suspected clinically in 31% of patients, but we were unsuccessful in microbiologically documenting any culture growth in blood, urine, or any other body fluid culture. The cause of fever remained a mystery and unknown to us without any microbiological or clinical cues in 119 cases (30%) of febrile neutropenic episodes.

Physiologically Based Pharmacokinetic Model To Predict Metoprolol Disposition in Healthy and Disease Populations.

The evolution in the development of drugs has increased the popularity of physiologically based pharmacokinetic (PBPK) models. This study seeks to assess the PK of metoprolol in populations with healthy, chronic kidney disease (CKD), and acute myocardial infarction (AMI) conditions by developing and evaluating PBPK models. An extensive literature review for identifying and selecting plasma concentration vs time profile data and other drug-related parameters was undergone for their integration into the PK-Sim program followed by the development of intravenous, oral, and diseased models. The developed PBPK model of metoprolol was then evaluated using the visual predictive checks, mean observed/predicted ratios (Robs/pre), and average fold error for all PK parameters, i.e., the area under the curve (AUC), maximal plasma concentration, and clearance. The model evaluation depicted that none of the PK parameters were out of the allowed range (2-fold error) in the case of the mean Robs/pre ratios. The model anticipations were executed to determine the influence of diseases on unbound and total AUC after the application of metoprolol in healthy, moderate, and severe CKD. The dosage reductions were also suggested based on differences in unbound and total AUC in different stages of CKD. The developed PBPK models have successfully elaborated the PK changes of metoprolol occurring in healthy individuals and those with renal and heart diseases (CKD & AMI), which may be fruitful for dose optimization among diseased patients.

A physiologically based pharmacokinetic model of cefepime to predict its pharmacokinetics in healthy, pediatric and disease populations.

The physiologically based pharmacokinetic modeling (PBPK) approach can predict drug pharmacokinetics (PK) by combining changes in blood flow and pathophysiological alterations for developing drug-disease models. Cefepime hydrochloride is a parenteral cephalosporin that is used to treat pneumonia, sepsis, and febrile neutropenia, among other things. The current study sought to identify the factors that impact cefepime pharmacokinetics (PK) following dosing in healthy, diseased (CKD and obese), and pediatric populations. For model construction and simulation, the modeling tool PK-SIM was utilized. Estimating cefepime PK following intravenous (IV) application in healthy subjects served as the primary step in the model-building procedure. The prediction of cefepime PK in chronic kidney disease (CKD) and obese populations were performed after the integration of the relevant pathophysiological changes. Visual predictive checks and a comparison of the observed and predicted values of the PK parameters were used to verify the developed model. The results of the PK parameters were consistent with the reported clinical data in healthy subjects. The developed PBPK model successfully predicted cefepime PK as observed from the ratio of the observed and predicted PK parameters as they were within a two-fold error range.

Direct oral anticoagulants vs. vitamin K antagonists in patients with antiphospholipid syndrome: a systematic review and meta-analysis.

Optimal treatment regimen for patients with antiphospholipid syndrome (APS) remain unclear. Therefore, the authors sought to compare the outcomes of vitamin K antagonists (VKAs) vs. direct oral anticoagulants (DOACs) in patients with APS. Methods: MEDLINE, Embase, and Cochrane Central databases were searched for randomized controlled trials comparing efficacy and safety of VKAs and DOACs inhibitors in patients with APS. Recurrent thrombosis, all-cause mortality, stroke, adverse reactions, and bleeding were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs. Results: The analysis included 625 patients from four randomized controlled trials and one post hoc analysis. Meta-analysis showed statistically non-significant difference between DOACs inhibitors and VKAs in the recurrent thrombosis risk (arterial or venous) [RR 2.77 (95%, CI 0.79, 9.65); P=0.11, I2=50%]. Consistent results were revealed among patients with the previous history of arterial thrombosis [RR 2.76 (95% CI 0.93, 8.16); P=0.75, I2=0%], venous thrombosis [RR 1.71 (95% CI 0.60, 4.84); P=0.31, I2=15%] and patients who were triple antiphospholipid positive [RR 4.12 (95% CI 0.46, 37.10); P=0.21, I2=58%]. DOACs inhibitors were significantly associated with increased risk of stroke [RR 8.51 (95% CI 2.35, 3.82); P=0.47, I2=0%]. Conclusion: DOACs exhibited increased risk of stroke among patients with APS. In addition, although not significant, the higher RRs among patients on DOACs may indicate higher risk of thrombotic events associated with DOACs.

Effects of transport-carbon intensity, transportation, and economic complexity on environmental and health expenditures.

Health and the environment are complex components of the countries, influenced by several factors, especially transport, and economics. Thus, this paper assesses the role of transportation and economic complexity in the environment and public health for the Organization for Economic Co-operation Development (OECD) countries from 2001 to 2020. This study also focuses on the relationship between transport and economic complexity with environmental and healthcare expenditures. Precisely, transport and economic activities stimulate healthcare expenditures through multiple channels. The current study employs the STIRPAT model to investigate the association with transportation, economic complexity, transport-carbon intensity, and healthcare expenditure. Besides, the current research confirms the plausible cross-sectional dependency across countries, and it adopts a second-generation technique. Analytical findings suggest that transportation-carbon intensity is positively and significantly associated with healthcare expenditures. Healthcare and transport-household expenditures increase transport-carbon intensity (TCI) by 75% and 45%, respectively, in the long run. In the contrast, TCI and transport-household expenditures have also a remarkable impact on healthcare expenditures and are estimated approximately 95% in the long run. Moreover, economic growth also upsurges TCI and healthcare expenditures through multiple economic activities. Besides, transport-household expenditures (THE) drastically impact transport-carbon intensity and healthcare expenditures (HEX) through passenger traffic (PTF). Diagnostic upshots unveil that the joint effect of THE and PTF increases TCI and HEX by 4 and 3%, respectively. Finally, findings recommend some policy implications and future research directions for the countries based on empirical outcomes. Countries should regulate economic activities to reduce transport carbon emissions.

Association of d-dimer levels with in-hospital outcomes among COVID-19 positive patients: a developing country multicenter retrospective cohort.

D-dimer levels, which originate from the lysis of cross-linked fibrin, are serially measured during coronavirus disease 2019 illness to rule out hypercoagulability as well as a septic marker. Methods: This multicenter retrospective study was carried out in two tertiary care hospitals in Karachi, Pakistan. The study included adult patients admitted with a laboratory-confirmed coronavirus disease 2019 infection, with at least one measured d-dimer within 24 h following admission. Discharged patients were compared with the mortality group for survival analysis. Results: The study population of 813 patients had 68.5% males, with a median age of 57.0 years and 14.0 days of illness. The largest d-dimer elevation was between 0.51-2.00 mcg/ml (tertile 2) observed in 332 patients (40.8%), followed by 236 patients (29.2%) having values greater than 5.00 mcg/ml (tertile 4). Within 45 days of hospital stay, 230 patients (28.3%) died, with the majority in the ICU (53.9%). On multivariable logistic regression between d-dimer and mortality, the unadjusted (Model 1) had a higher d-dimer category (tertile 3 and tertile 4) associated with a higher risk of death (OR: 2.15; 95% CI: 1.02-4.54, P=0.044) and (OR: 4.74; 95% CI: 2.38-9.46, P<0.001). Adjustment for age, sex, and BMI (Model 2) yields only tertile 4 being significant (OR: 4.27; 95% CI: 2.06-8.86, P<0.001). Conclusion: Higher d-dimer levels were independently associated with a high risk of mortality. The added value of d-dimer in risk stratifying patients for mortality was not affected by invasive ventilation, ICU stays, length of hospital stays, or comorbidities.

Effect of Transport Properties of Crystalline Transition Metal (Oxy)hydroxides on Oxygen Evolution Reaction.

Electronic transport plays a pivotal role in the electrolysis of semiconducting electrocatalysts for oxygen evolution reaction (OER), while it is mostly underestimated and largely unexplored. Here, by investigating the electronic transport behavior of seven archetypical crystalline Co/Ni/Fe-based (oxy)hydroxides (unary, binary, and ternary) under OER potential, we study how and the extent to which it affects the apparent catalytic performances. The electronic transports of unary metal (oxy)hydroxides follow the order of Co > Ni > Fe, and their binary or ternary compounds can generally impose one order of magnitude higher electrical conductivity. By studying the dependence of catalytic performances on electrical conductivities, we further unveil that charge transportability not only determines the electronic accessibility of catalytic nanoparticles but also, to our surprise, regulates the reaction kinetics of the electronically accessible active sites. Remarkably, the regulation extent of reaction kinetics correlates with the electrical conductivities of electrocatalysts, suggesting that the electrocatalytic process is strongly coupled with electronic transport. The work presents an overview of electronic transports of crystalline (oxy)hydroxides under OER potentials and highlights their pivotal role in unfolding catalytic potential, holding both fundamental and technical implications for the screen and design of efficient electrocatalysts.

Clinical pharmacokinetics of cefixime: a systematic review.

Cefixime is an antibiotic from the cephalosporin class used to treat various bacterial infections. The purpose of performing this review is to thoroughly evaluate the pharmacokinetic (PK) data on cefiximeFive databases were systematically searched to identify studies on the PK of cefixime.A total of 38 articles meeting the eligibility criteria were included that provide data on concentration-time profiles or PK parameters such as peak plasma and serum concentration (Cmax), area under the curve (AUC), clearance (CL), and time to reach Cmax (tmax). A dose-dependent increase in AUC and Cmax of cefixime was depicted in healthy volunteers. The clearance of cefixime decreased according to the degree of renal insufficiency among haemodialysis patients. A significant difference in CL was found in comparing fasted and fed states. A biphasic decline in serum concentrations of cefixime was reported when it was taken without probenecid.This review compiles all the reports on the PK of cefixime in healthy and really impaired patients; the summarised information can be used to optimise cefixime dosing in different disease states. Moreover, cefixime has increased time above MIC value suggesting that it may be an effective treatment for infections caused by certain pathogens.

Endoscopic ultrasound-guided liver biopsy using a single-pass, slow-pull technique with a 19-G Franseen tip fine-needle biopsy needle: A prospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is considered to be safe and effective. Commonly a 19-G fine-needle aspiration or biopsy needle is used. But, the results vary with different techniques that are used. Herein, we report the results of liver biopsy with a single-pass, three actuations (1:3) using the slow-pull technique. METHODS: In this prospective study, 50 consecutive patients with indications for liver biopsy underwent EUS-LB with a 19-gauge fine-needle biopsy (FNB) needle from both right and left lobes. The primary outcome was the adequacy of the specimen for histological diagnosis. Total specimen length (TSL), longest specimen length (LSL), complete portal tracts (CPTs) and comparison of these outcomes between the left lobe and right lobe specimens were secondary outcomes. Adverse events (AEs) were also measured during this study. RESULTS: Adequate tissue for histological diagnosis was obtained in all 50 patients (100%). The median number of CPTs was 32.5 (range, 11-58), while the median of TSL was 58 mm (range, 35-190) and the median LSL was 15 mm (range, 5-40). There was no significant difference in CPTs, TSL and LSL between left and right lobe biopsies. There was no major complication; one of the patients (2%) had bleed from the duodenal puncture site, which was managed endoscopically without the need for blood transfusion. CONCLUSIONS: Endoscopic ultrasound-guided liver biopsy using a 19-gauge Franseen tip needle with a single pass, three actuation (1:3) and slow-pull technique provides adequate tissue yield and has a good safety profile.

Determinants of bank's efficiency in an emerging economy: A data envelopment analysis approach.

This study aims to assess the influence of internal and external factors on the Efficiency of banks in Pakistan using the Data Envelopment Analysis Approach (DEA). Bank's Efficiency is measured through DEA Model using input and output variables. The input variable includes the number of employees, number of branches, administration expenses, non-interest expenses, and loan loss provisions. In contrast, the output variable consists of net interest income, net commissions, and total other income. This study considers the internal determinants of the bank's Efficiency as corporate governance, enterprise risk management, ownership structure (state, foreign, and domestic ultimate owned banks), return on equity, financial leverage, and the size of the bank. The external determinants of the bank's Efficiency include banking structure and macroeconomic conditions. The study has used data from seventeen commercial banks over the period of 2011 to 2020. The study used the Data Envelopment Analysis Approach (DEA) and Logit and Probit Regression Model to evaluate research hypotheses. The Logit model results show that corporate governance, ultimate global ownership, and return on equity have a statistically significant and positive impact on the bank's Efficiency. Enterprise risk management and financial leverage adversely affect the bank's Efficiency. Better corporate governance can help banks to control the risk and cost of capital and enhancement the effectiveness of capital. Similarly, better risk management of banks can lead to better operational and strategic decisions in the competitive banking environment.

Assessment of risk factors associated with potential drug-drug interactions among patients suffering from chronic disorders.

Patients suffering from chronic diseases are more likely to experience pDDIs due to older age, prolonged treatment, severe illness and greater number of prescribed drugs. The objective of the current study was to assess the prevalence of pDDIs and risk factors associated with occurrence of pDDIs in chronic disease patients attending outpatient clinics for regular check-ups. Patients suffering from diabetes, chronic obstructive pulmonary disease (COPD), stroke and osteoporosis were included in the study. This study was a cross sectional, observational, prospective study that included 337 patients from outpatient clinics of respiratory ward, cardiac ward and orthopedic ward of Nishter Hospital Multan, Pakistan. The mean number of interactions per patient was 1.68. A greater risk for occurrence of pDDI was associated with older age ≥ 60 years (OR = 1.95, 95% CI = 1.44-2.37, p<0.001); polypharmacy (≥ 5 drugs) (OR = 3.74, 95% CI 2.32-4.54, p<0.001); overburden (OR = 2.23, 95% CI = 1.64-3.16, p<0.01); CCI score (OR = 1.28, 95% CI = 1.04-1.84, p<0.001); multiple prescribers to one patient (OR = 1.18, 95% CI = 1.06-1.41, p<0.01); and trainee practitioner (OR = 1.09, 95% CI = 1.01-1.28, p<0.01). Old age, polypharmacy, overburden healthcare system, higher comorbidity index, multiple prescribers to one patient and trainee practitioner were associated with increased risk of occurrence of pDDIs in chronic disease patients.

Clinical pharmacokinetics of terbutaline in humans: a systematic review.

Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (Cp) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (Tmax) was prolonged, and maximum plasma concentration (Cmax) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the Cp of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions.

Prevalence Of Second Mesiobuccal Canal In Maxillary Second Molars On The Basis Of Clinical And Radiographic Parameters.

BACKGROUND: The objective of this study was to determine the prevalence of the second mesiobuccal canal in permanent maxillary second molar in patients presenting to Peshawar Dental College and Hospital. METHODS: One hundred and twenty patients advised for root canal treatment in the maxillary second molars participated in the study. Two detection procedures, clinical and radio graphical examination were used. Two pre-operative radiographs with different angulations and one post-operative radiograph were taken to examine roots and root canals. Access cavities were prepared and the second mesiobuccal canal was explored using magnifying dental loupes (3.5 x), endodontic explorer (DG16) and size 10 K-file. Descriptive statistics were recorded as percentages, frequencies and mean. The chi-square test was used for gender, age-wise comparison and right and left side of the maxillary jaw. RESULTS: One hundred and twenty patients were recruited in the study. There were 65 (54.2%) males and 55 (45.8%) females. The second mesiobuccal canal was more common in males compared to females (p-value=0.434). The second mesiobuccal canal was most commonly found in 3rd decade with mean age, of 40.5±12.31, (p-value =0.51). The frequencies and percentages of the second mesiobuccal canal in maxillary second molars on the right and left side of the jaw were 70 (58.3%) and 50 (41.7%) respectively (p-value =0.310). CONCLUSIONS: The second mesiobuccal canal was found in less than half of the second molars. The most successful method of detection in this study was both clinical and radiographic.

Machine learning evaluation of LV outflow obstruction in hypertrophic cardiomyopathy using three-chamber cardiovascular magnetic resonance.

Left ventricular outflow tract obstruction (LVOTO) is common in hypertrophic cardiomyopathy (HCM), but relationships between anatomical metrics and obstruction are poorly understood. We aimed to develop machine learning methods to evaluate LVOTO in HCM patients and quantify relationships between anatomical metrics and obstruction. This retrospective analysis of 1905 participants of the HCM Registry quantified 11 anatomical metrics derived from 14 landmarks automatically detected on the three-chamber long axis cine CMR images. Linear and logistic regression was used to quantify strengths of relationships with the presence of LVOTO (defined by resting Doppler pressure drop of > 30 mmHg), using the area under the receiver operating characteristic (AUC). Intraclass correlation coefficients between the network predictions and three independent observers showed similar agreement to that between observers. The distance from anterior mitral valve leaflet tip to basal septum (AML-BS) was most highly correlated with Doppler pressure drop (R2 = 0.19, p < 10-5). Multivariate stepwise regression found the best predictive model included AML-BS, AML length to aortic valve diameter ratio, AML length to LV width ratio, and midventricular septal thickness metrics (AUC 0.84). Excluding AML-BS, metrics grouped according to septal hypertrophy, LV geometry, and AML anatomy each had similar associations with LVOTO (AUC 0.71, 0.71, 0.68 respectively, p = ns), significantly less than their combination (AUC 0.77, p < 0.05 for each). Anatomical metrics derived from a standard three-chamber CMR cine acquisition can be used to highlight risk of LVOTO, and suggest further investigation if necessary. A combination of geometric factors is required to provide the best risk prediction.

Diagnostic dilemma of celiac disease presenting with weight loss and secondary amenorrhea: A case report.

RATIONALE: Celiac disease (CD) is autoimmune enteropathy affecting the proximal small intestinal mucosa. It is caused by insensitivity to gluten, a protein predominantly presented in wheat. CD is classically associated with gastrointestinal symptoms. The non-classic clinical presentation of CD can present with other organ involvement. Non-human leukocyte antigens genes are associated with atypical forms. PATIENTS CONCERN: We reported a case of 30-year-old female who presented with progressive pallor, amenorrhea, and unexplained weight loss with generalized body weakness. Her body mass index was 20. The patient was having no other systemic manifestations. DIAGNOSIS: This paper reports a case of a female patient having CD without its typical features. Her laboratory evaluation revealed microcytic anemia. Anti-TTg IgA and Anti-TTG IgG antibodies were raised, ferritin and folate were low, and there was mild hyperbilirubinemia. However, follicle-stimulating hormone, luteinizing hormone, and serum estradiol levels were normal. She was diagnosed with a case of anemia resulting from malabsorption caused by CD. INTERVENTIONS: A management plan was devised based on a strict gluten-free diet. The patient received supplements containing folates, iron, calcium, zinc, and vitamins A, D, E, B6, and B12. OUTCOMES: After 3 months of treatment with strict gluten-free diet patient showed remarkable improvement. Her hemoglobin level raised with weight gain. Her normal menstrual cycle was restored with complete resolution of symptoms at 1 year follow-up. LESSONS: The pathogenesis of the atypical CD is multifactorial, but impaired uptake of micronutrients from the duodenum is the most likely cause, even if other common features of classical forms, such as bloating and diarrhea, are absent. Lack of awareness about atypical forms may lead to under-diagnoses of the disease. The physicians should consider the atypical presentations of CD to avoid the under-diagnoses of this multisystem disorder.