Gallstone Disease and Its Correlation With Thyroid Disorders: A Narrative Review.

Over the years, several studies have revealed an important link between thyroid disorders and gallstone disease. According to these studies, hypothyroidism and hyperthyroidism are associated with cholesterol gallstone disease. This association between thyroid hormone disorders and cholesterol gallstone disease is due to the importance of thyroid hormones on cholesterol synthesis, bile functioning and content, and gallbladder motility. Several genes and receptors have been found on the thyroid gland, liver, and gallbladder to verify this association. These genes affect thyroid hormone secretion, lipid metabolism, and bile secretion. Defects in these various gene expression and protein functions lead to bile duct diseases. Other causes that lead to cholesterol gallstone disease are supersaturation of the bile with cholesterol and impaired gallbladder motility, which leads to bile stasis. This article has discussed these factors in detail while highlighting the association between thyroid hormones and cholesterol gallstone disease.

Central Diabetes Insipidus: An Acute Manifestation of COVID-19 Infection.

In recent years, there has been a rise in the number of COVID-19 cases and its complications. Central diabetes insipidus (central DI) is a rare but treatable manifestation of acute COVID-19 infection. This case reports the rapid onset of central DI in a 35-year-old male in less than two weeks post-COVID-19 infection. He made a complete recovery post-administration of desmopressin within one month. Prompt diagnosis, treatment, and periodic follow-up are hence the cornerstones of a successful recovery for a patient with central DI post-COVID-19 infection.

Outcomes of Neurorehabilitation Among Patients With Prolonged Disorders of Consciousness.

BACKGROUND:  The impact of neurorehabilitation on patients with prolonged disorders of consciousness (PDOC) is not well known. We assessed the range of motion (ROM), muscle girth and power, level of consciousness, development of musculoskeletal deformity, and superficial sensation. METHODS:  A retrospective observational record-based study was done, which included the data of patients diagnosed with PDOC admitted at Thumbay Physical Therapy & Rehabilitation Hospital, Ajman, UAE, between 2020 and 2022. Data on the "range of motion", "muscle girth and power", "level of consciousness", "development of musculoskeletal deformity", and "superficial sensation" were collected and analyzed. The SPSS software version 27 (IBM Corp., Armonk, NY, USA) was used for analysis. The chi-square test was used to assess association, and the t-test was used to test the mean difference. RESULTS:  We assessed the data of 21 patients with PDOC. The superficial sensation was found to have increased significantly (p<0.025). There was a decrease in the proportion of patients with musculoskeletal deformities during the follow-up period. The ROM, muscle girth, and muscle power were also preserved without significant deterioration. However, the level of consciousness measured by the Glasgow coma scale (GCS) showed no improvement. CONCLUSIONS: Our research showed that neurorehabilitation significantly improves superficial sensation and prevents the development of musculoskeletal deformities. However, the mean level of consciousness remained the same. There was also no decrease in ROM. Both muscle girth and power were preserved over two years.

Clinico-Radiological-Pathologic Profile and Outcomes of Lung Transplant in Post-COVID-19 Phenotype: A Single Center Experience.

BACKGROUND: Lung transplantation (LTx) has come as hope for select patients with post-COVID acute respiratory distress syndrome (ARDS). It has a different phenotype with unique challenges. We aimed to bring out our experience with and outcomes of LTx for post-COVID ARDS. METHODS: This study is retrospective case series from a single center in India. All the patients with post-COVID end stage lung disease (ESLD) who underwent bilateral LTx between 1st May 2020 and 30th August 2021 were included. LTx was performed following no improvement with optimal medical management with adequate time provided for recovery. Information relating to demographics, comorbidities, pretransplant status, perioperative parameters, gross and histopathological findings of explanted lungs, posttransplant morbidity, and mortality were analyzed. RESULTS: This study included 23 patients. The median age of the patients in this study was 42 years and 20 participants were men (87%). The mean duration of intensive care unit stay was 15.83 ± 6.61 days. Mortality was observed among 8 participants (34.78%). Mean survival time was 34.54 weeks. Among the 8 patients who expired, the cause of death was sepsis for 6 patients (75.0%), neurologic cerebrovascular accident for 1 patient (12.5%), and cytomegalovirus for 1 patient (12.5%). All the deaths were reported in primary graft dysfunction grade 2 & 3 category. No rejections were observed on first and third month surveillance biopsies. CONCLUSIONS: LTx is the definitive option for survival in select patients with severe post-COVID-19-associated ESLD. This study brings out various challenges involved in such phenotypes and also observations in postoperative recovery.

ReCODE: A Personalized, Targeted, Multi-Factorial Therapeutic Program for Reversal of Cognitive Decline.

BACKGROUND: Alzheimer's disease (AD) is the major cause of age-associated cognitive decline, and in the absence of effective therapeutics is progressive and ultimately fatal, creating a dire need for successful prevention and treatment strategies. We recently reported results of a successful proof-of-concept trial, using a personalized, precision medicine protocol, but whether such an approach is readily scalable is unknown. OBJECTIVE: In the case of AD, there is not a single therapeutic that exerts anything beyond a marginal, unsustained, symptomatic effect. This suggests that the monotherapeutic approach of drug development for AD may not be an optimal one, at least when used alone. Using a novel, comprehensive, and personalized therapeutic system called ReCODE (reversal of cognitive decline), which proved successful in a small, proof-of-concept trial, we sought to determine whether the program could be scaled to improve cognitive and metabolic function in individuals diagnosed with subjective cognitive impairment, mild cognitive impairment, and early-stage AD. METHODS: 255 individuals submitted blood samples, took the Montreal Cognitive Assessment (MoCA) test, and answered intake questions. Individuals who enrolled in the ReCODE program had consultations with clinical practitioners, and explanations of the program were provided. Participants had follow-up visits that included education regarding diet, lifestyle choices, medications, supplements, repeat blood sample analysis, and MoCA testing between 2 and 12 months after participating in the ReCODE program. Pre- and post-treatment measures were compared using the non-parametric Wilcoxon signed rank test. RESULTS AND CONCLUSIONS: By comparing baseline to follow-up testing, we observed that MoCA scores either significantly improved or stabilized in the entire participant pool-results that were not as successful as those in the proof-of-concept trial, but more successful than anti-amyloid therapies-and other risk factors including blood glucose, high-sensitivity C-reactive protein, HOMA-IR, and vitamin D significantly improved in the participant pool. Our findings provide evidence that a multi-factorial, comprehensive, and personalized therapeutic program designed to mitigate AD risk factors can improve risk factor scores and stabilize or reverse the decline in cognitive function. Since superior results were obtained in the proof-of-concept trial, which was conducted by a small group of highly trained and experienced physicians, it is possible that results from the use of this personalized approach would be enhanced by further training and experience of the practicing physicians. Nonetheless, the current results provide further support indicating the potential of such an approach for the prevention and reversal of cognitive decline.

Challenges, experiences, and postoperative outcomes in setting up first successful lung transplant unit in India.

BACKGROUND: Lung transplantation (LT) has emerged as a definitive cure for a plethora of end-stage lung diseases (ESLDs). With improvements in immune-suppression protocols, the posttransplantation survival rates have gone up. AIM: The study reported the initial experience of the India's single largest lung transplant program on clinicopathological profile, procedures, challenges encountered, and outcomes. SETTINGS AND DESIGN: A retrospective analysis was done from data available at three centers of Institute of Heart and Lung Transplant, Gleneagles Global Hospitals across Chennai, Bengaluru, and Mumbai. MATERIALS AND METHODS: A total of 132 patients underwent lung (single or bilateral) or combined heart and lung transplant between April 2017 and March 2020. All the participants had 30 days' follow-up. Postoperative complications, graft rejection, and 30-day mortality were reported. Kaplan-Meier survival analysis and logistic regression analysis were performed. STATISTICAL ANALYSIS USED: Kaplan-Meier survival and binary logistic regression was performed. RESULTS: Interstitial lung diseases, 65.91%, were the most common diagnosis. Bilateral LT (81.3%) was the most common type of LT performed. Grade III primary graft dysfunction was observed in 16 (12.1%). Distal airway stenosis (21.97%) was the most common complication followed by anastomotic stenosis (14.30%). Gram-negative bacterial sepsis (52%) was the leading cause of death. Cumulative probability of survival at 1 month was 0.85 (95% confidence interval [CI] 0.80-0.92), and at 1 year, it was 0.78 (95% CI, 0.72-0.86). CONCLUSION: This study establishes the fact that despite multiple challenges, LT is a viable option for selected patients with ESLDs in India and should encourage early referrals to a transplant center.

Estimating the economic burden of migraine on US employers.

Migraine is a leading cause of disability globally. Individuals with migraine experience reduced work productivity and greater health care costs compared with the general population. The Migraine Impact Model (MIM) is an interactive calculator developed to estimate the economic burden of migraine on United States-based employers. We demonstrate use of the model with 4 case studies from different industries (education, manufacturing, retail/trade, and entertainment). The MIM estimates migraine prevalence among employees and the employer's annual migraine-associated costs by applying published, licensed, and publicly available data and several underlying assumptions to employee population information that is inputted by users. User inputs include the employer's industry, geographic location, and workforce characteristics (number of employees, gender distribution, and average age and compensation). Model outputs include estimated migraine prevalence, annual workdays affected by migraine, and annual migraine-associated indirect and direct costs to the employer. In the case studies presented, workforce size ranged from 18,800 to 250,000, representing midsized to larger employers. Employee gender distribution ranged from 29% to 74% women, and mean employee age was either 41 or 44 years. The model-estimated percentage of employees with migraine ranged from 14% to 19%. The model projected approximately 60,000 to 686,000 annual workdays to be affected by lost productive time due to migraine (often referred to as "absenteeism" and "presenteeism") and estimated annual indirect costs to total between 6.2 and 8.5 times the annual direct costs. The MIM estimates the economic burden of migraine on a company's workforce, which may aid employers in making data-driven decisions to reduce that burden for employees and business.

N-terminal domain of the androgen receptor contains a region that can promote cytoplasmic localization.

Nucleocytoplasmic trafficking of the androgen receptor (AR) represents an essential step in androgen action. To determine whether the amino-terminal domain (NTD) contains potential nuclear import and/or export signals, deletion mutants of the NTD tagged with green fluorescent protein (GFP) were generated and tested for their intracellular localization in both AR-negative and AR-positive cell lines. Subcellular localization analysis suggested a role of the NTD in regulating AR subcellular localization and revealed that the region of a.a. 50-250 of the NTD of AR (AR(50-250)) could promote cytoplasmic localization. Leptomycin B inhibited the activity of AR(50-250), suggesting that AR(50-250) export is mediated through exportin 1, either directly or indirectly. These observations argue for an important role of the NTD in regulating AR nucleocytoplasmic trafficking and will facilitate further investigation of interactions among different signals in regulating AR nucleocytoplasmic trafficking, which may lead to new approaches to inhibit AR nuclear localization.

Growth modulation using functional appliances--cephalometric predictors of successful response.

AIM: The aim of this study was to determine any skeletal morphologic features evident on a pretreatment lateral cephalogram that may be used to predict improvement in the sagittal relationship during functional appliance therapy in Class II patients and compare changes between cases with and without a favorable response to growth modulation. METHOD: Pretreatment and postfunctional lateral cephalograms were analyzed, and the change in the ANB angle was used to determine the skeletal response to treatment with a functional appliance. Based on the change in the ANB angle, the patients were divided into two groups of 12 patients each. Comparisons were made between the mean pretreatment (T1) cephalometric parameters of group I (skeletal) and group II (nonskeletal) to assess any pretreatment parameters that were significantly different between the groups. Changes due to functional appliance therapy from the pretreatment (T1) to postfunctional (T2) stage was measured as T2-T1 in both groups. The mean changes seen in group I and group II were then compared to assess the difference between changes brought about by growth modulation using functional appliances. Comparative statistical analysis of the data was done using one-way analysis of variance F test. RESULTS AND CONCLUSION: This study showed that not all cases respond favorably to growth modulation. The pretreatment parameters that correlated to a favorable response were low mandibular plane angle, low basal plane angle, and a high Jarabak ratio. In those cases that responded favorably, the changes seen were an increase in Co-Go (ramus height), decrease in overjet, increase in SNB, and increase in the Jarabak ratio.

The BASIL survival prediction model in patients with peripheral arterial disease undergoing revascularization in a university hospital setting and comparison with the FINNVASC and modified PREVENT scores.

BACKGROUND: Critical limb ischemia carries a significant risk of morbidity and mortality. The development of scores to predict risk can aid clinical decision making. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial investigators developed a model to predict death, which has not been previously validated. METHODS: Data were collected in a prospectively maintained database on all patients who underwent angioplasty or arterial bypass for peripheral artery disease in a university hospital between January 2008 and June 2010. The main outcome measures were all-cause mortality and amputation-free survival at 3, 6, 12, and 24 months after the index intervention. The BASIL survival predictor, Finland National Vascular (FINNVASC) registry, and Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) models were applied and receiver-operating characteristic (ROC) curve analysis was used to evaluate their predictive power. RESULTS: Data on 342 patients were collected. Patients with isolated iliac disease or claudication were excluded. The 6-, 12-, and 24-month all-cause mortality rates were 11.6%, 17.9%, and 26.8%, respectively. The area under the ROC curve (95% confidence interval) using the BASIL score to predict mortality at 6, 12, and 24 months was 0.700 (0.60-0.80; P<.001), 0.651 (0.56-0.74; P<.003), and 0.681 (0.59-0.74; P<.001), respectively. ROC curve analysis indicated that the performance of the BASIL score in this cohort was comparable to other validated predictive scores. CONCLUSIONS: The BASIL survival prediction model can moderately predict short-term and medium-term mortality in patients with limb ischemia and may be a useful adjunct to decision making in everyday clinical practice.

Predictive value of peak systolic velocity for the development of graft limb complications after endovascular aneurysm repair.

PURPOSE: To determine the role of peak systolic velocity (PSV) data provided by duplex ultrasound (DUS) surveillance in the prediction of endograft limb complications after endovascular aneurysm repair (EVAR). METHODS: All 478 consecutive patients (425 men; mean age 75±7 years) who underwent infrarenal EVAR between 2004 and 2010 had DUS scans at 1.5, 3, 6, 9, 12, and 18 months and annually thereafter over a median follow-up of 43 months (range 1-92). In a retrospective study, the PSV recorded from the proximal and distal regions of each stent-graft limb was extracted from each postoperative DUS scan for each patient up to the penultimate scan before diagnosis of a limb complication (limb occlusion, symptomatic or hemodynamically significant kinking, or hemodynamically significant DUS-defined stenosis) requiring reintervention. The median (range) PSV readings from the proximal and distal regions of each stent-graft limb over the course of follow-up were compared between patients who developed a limb complication (n = 38) and those who did not (n = 440). Time-dependent Cox proportional hazards modeling was performed after risk adjustment; results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the proximal stent-graft limb segment, the median PSV was 106 cm/s (42-308) in patients without limb complications vs. 121 cm/s (50-281) in those with limb complications. Corresponding values in the distal segment of the endograft limb were 113 cm/s (35-400) vs. 129 cm/s (58-420). After risk adjustment, increased PSV over time within both the proximal and distal segments of the stent-graft limb was significantly associated with the risk of limb complications (proximal HR 1.015, 95% CI 1.003 to 1.028, p = 0.014; distal HR 1.010, 95% CI 1.001 to 1.020, p = 0.025). CONCLUSION: Increases in the peak systolic velocity in stent-graft limbs were associated with an increased risk of limb complication, though no predictive threshold could be identified from scans prior to the development of a complication. This observation requires external validation and further investigation to define its clinical utility.