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Rare heterozygous loss-of-function mutations of the MAX gene are associated with autosomal dominant hereditary pheochromocytoma-paraganglioma syndrome. In addition, evidence suggests that pathogenic MAX mutation may predispose to the development of other tumors, including endocrine and nonendocrine tumors, although the number of reported cases is small. We report a 67-year-old man with bilateral pheochromocytoma, primary hyperparathyroidism, prostate cancer, neurofibroma, and abdominal wall lipoma who tested positive for a heterozygous pathogenic germline MAX mutation. The patient has a history of bilateral norepinephrine-producing pheochromocytomas, for which he underwent left and right adrenalectomy in his 20s and 30s, respectively. His long-standing primary hyperparathyroidism was first documented when he was 40 years old and complicated by recurrent bilateral calcium oxalate nephrolithiasis and early-onset osteoporosis. Genetic testing revealed a heterozygous pathogenic deletional frameshift mutation of the exon 4 of the MAX gene (c.183_195del; p.Gln62Lysfs*104). This report, together with 3 previously reported cases, suggests that germline MAX mutation may contribute to the development of primary hyperparathyroidism and may be considered in suspected genetic forms of this disease.

BACKGROUND Obese and malabsorptive patients have difficulty increasing serum 25-hydroxyvitamin D [25(OH)D] after taking vitamin D supplementation. Since 25(OH)D is more hydrophilic than vitamin D, we hypothesized that oral 25(OH)D supplementation is more effective in increasing serum 25(OH)D concentrations in these patients. OBJECTIVES We aimed to investigate the pharmacokinetics of oral 25-hydroxyvitamin D3 [25(OH)D3] and oral vitamin D3 in healthy participants with differing BMI and malabsorptive patients. METHODS A randomized, double-blind crossover trial was performed in 6 malabsorptive patients and 10 healthy participants who were given 900 µg of either vitamin D3 or 25(OH)D3 orally followed by a pharmacokinetic study (PKS). After ≥28 d from the first dosing, each participant returned to receive the other form of vitamin D and undergo another PKS. For each PKS, serum vitamin D3 and 25(OH)D3 were measured at baseline and at 2, 4, 6, 8, and 12 h and days 1, 2, 3, 7, and 14. Pharmacokinetic parameters were calculated. RESULTS Data were expressed as means ± SEMs. The PKS of 900 µg vitamin D3 revealed that malabsorptive patients had 64% lower AUC than healthy participants (1177 ± 425 vs. 3258 ± 496 ng · h/mL; P

Background: Studies have demonstrated the link between vitamin D-related genetic variations and non-skeletal outcomes. We aimed to identify all available data on the association of vitamin D-related genetic variations with non-alcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible study must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3,495 articles were identified. After systematic review, twelve studies were in-cluded. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indi-cating the role of vitamin D in the pathogenesis of NAFLD.

Hereditary metabolic bone diseases are characterized by genetic abnormalities in skeletal homeostasis and encompass one of the most diverse groups among rare diseases. In this review, we examine 25 selected hereditary metabolic bone diseases and recognized genetic variations of 78 genes that represent each of the three groups, including sclerosing bone disorders, disorders of defective bone mineralization and disorder of bone matrix and cartilage formation. We also review pathophysiology, manifestation and treatment for each disease. Advances in molecular genetics and basic sciences has led to accurate genetic diagnosis and novel effective therapeutic strategies for some diseases. For other diseases, the genetic basis and pathophysiology remain unclear. Further researches are therefore crucial to innovate ways to overcome diagnostic challenges and develop effective treatment options for these orphan diseases.

PurposeThis study aimed to investigate the association between asthma and risk of myasthenia gravis (MG) using the method of systematic review and meta-analysis.MethodsPotentially eligible studies were identified from Medline and EMBASE databases from inception to … using search strategy that comprised of terms for “Asthma” and “Myasthenia Gravis”. Eligible cohort study must consist of one cohort of individuals with asthma and another cohort of individuals without asthma. Then, the study must report relative risk (RR) with 95% confidence intervals (95% CIs) of incident MG between the groups. Eligible case-control studies must include cases with MG and controls without MG. Then, the study must explore their history of asthma. Odds ratio (OR) with 95% CIs of the association between asthma status and MG must be reported. Point estimates with standard errors were retrieved from each study and were combined together using the generic inverse variance method.ResultsA total of 6,835 articles were identified. After two rounds of independent review by five investigators, two cohort studies and three case-control studies met the eligibility criteria and were included into the meta-analysis. Pooled analysis showed that asthma was significantly associated with risk of MG with the pooled risk ratio of 1.38 (95%CI, 1.02 – 1.86). Funnel plot was symmetric.Conclusion The current study found a significant association between asthma and increased risk of MG.

Objective To determine the association between vitamin D status and morbidity and mortality in adult hospitalized coronavirus disease 2019 (COVID-19) patients Methods We performed a retrospective chart review study in COVID-19 patients aged ≥18 year hospitalized at Boston University Medical Center between March 1 and August 4, 2020. All studied patients tested positive for COVID-19 and had serum levels of 25-hydroxyvitamin D (25[OH]D) results measured within 1 year prior to the date of positive tests. Medical information was retrieved from the electronic medical record and was analyzed to determine the association between vitamin D status and hospital morbidity and mortality. Results Among the 287 patients, 100 (36%) were vitamin D sufficient (25[OH]D >30 ng/mL) and 41 (14%) died during hospitalization. Multivariate analysis in patients aged ≥65 years revealed that vitamin D sufficiency (25[OH]D ≥30 ng/mL) was statistically significantly associated with decreased odds of death (adjusted OR 0.33, 95% CI, 0.12-0.94), acute respiratory distress syndrome (adjusted OR 0.22, 95% CI, 0.05-0.96), and severe sepsis/septic shock (adjusted OR 0.26, 95% CI, 0.08-0.88), after adjustment for potential confounders. Among patients with body mass index Conclusion We revealed an independent association between vitamin D sufficiency defined by serum 25(OH)D ≥30 ng/mL and decreased risk of mortality from COVID-19 in elderly patients and patients without obesity.

Background: Patients with psoriasis may have a higher risk of dementia because of the higher inflammatory burden, although results from previous epidemiological studies have been inconsistent. Aims: To determine the association between psoriasis and risk of dementia by pooling the evidence from previous studies. Methods: Potentially eligible studies were identified from Medline and EMBASE databases from inception to July 2019 using a search that comprised terms for “psoriasis” and “dementia.” Studies were eligible for the meta-analysis if they were cohort studies that included psoriatic patients and individuals without psoriasis and followed them for incident dementia. Studies were also required to report standardized incidence ratio, hazard risk ratio or relative risk with related 95% confidence intervals (CI) comparing the incidence of dementia between the two cohorts. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model, generic inverse variance method. Results: A total of 8,861 articles were identified. After two rounds of independent review by three investigators, we included six cohort studies that met the eligibility criteria in the meta-analysis. The risk of dementia was significantly higher among psoriatic patients than in those without psoriasis with a pooled risk ratio of 1.16 (95% CI, 1.04–1.30; I2 95%). A funnel plot was relatively symmetric and was not suggestive of the presence of publication bias. Limitations: Limited accuracy of diagnosis of psoriasis and dementia as four included studies were coding-based studies, and high statistical heterogeneity among studies. Conclusion: This systematic review and meta-analysis indicates that psoriatic patients have a significantly elevated risk of developing dementia.

Funding Acknowledgements Type of funding sources: None. Background/objectives: Recent studies have suggested that patients with premature ventricular complexes (PVCs) may have a higher risk of ischemic stroke. However, the data are limited and inconclusive. We conducted a systematic review and meta-analysis to investigate the association between PVCs and the risk of ischemic stroke. Methods A comprehensive literature review was conducted by searching for published articles indexed in MEDLINE and EMBASE databases from inception through September 25, 2020, to identify studies that compared the risk of ischemic stroke between patients with PVCs and individuals without PVCs. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of Dersimonian and Laird. Results A total of four observational studies (2 prospective and 2 retrospective cohort studies) with 42,677 participants met the eligibility criteria and were included in the meta-analysis. We found that patients with PVCs have a significantly higher risk of ischemic stroke than individuals without PVCs with the pooled RR of 1.31 (95% CI, 1.07-1.60, I2 = 43%). Conclusions: From our systematic review and meta-analysis, we found that PVCs are associated with a higher risk of ischemic stroke. Whether this association is causal and how it should be addressed in clinical practice require further investigations. Table 1Ofoma et al.Agarwal et al.Lin et al.Im et al.Year of publication2012201520152018Country of originUnited StatesUnited StatesTaiwanKoreaStudy designProspective cohort studyProspective cohort studyRetrospective cohort studyRetrospective cohort studyStudy subjectsCases: Cases were patients with PVCs who were diagnosed based on 2-minute ECG. Cases were identified from the 1987 to 1989 ARIC study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. The average follow-up time was 13 years. Patients with a history of stroke, CAD, SAH, and ICH were excluded from the analysis.Cases: Cases were patients with PVCs who were diagnosed based on routine ECG. Cases were identified from the 2003 to 2007 REGARDS study. Comparators: Comparators were the rest of the patients in the study who did not carry a diagnosis of PVCs. An average (SD) follow-up time was 6 (2) years. Patients with a history of stroke or TIA and hemorrhagic stroke were excluded from the analysis.Cases: Cases were patients with PVCs ( 720 beats/day were excluded from the analysis.Cases: Cases were patients with PVCs (>10%) who were diagnosed based on standard ECG or 24-hour ECG monitoring. Cases were identified from the 2013 to 2015 Kosin University database. Comparators: Comparators were the rest of the patients in the database who did not carry a diagnosis of PVCs. The average follow-up time was 4 years. Patients with a history of cardiomyopathy, VHD, CHD, hepatic or renal disease, and acute cardiovascular or cerebrovascular event within 3 months, any trauma or surgery within 3 months, hyperthyroidism, uncontrolled HT, malignancy, CTD, IHD, and any acute or chronic inflammatory disease were excluded from the analysis.Number of subjectsCases: 793Comparators: 13,700Cases: 1,415Comparators: 23,045Cases: 1,074 (Uniform PVCs), 1,166 (Multiform PVCs)Comparators: 1,111Cases: 203Comparators: 170Baseline characteristics of subjectsMean age, year: Cases: 55.97Comparators: 53.85 Mean BMI, kg/m2:Cases: 28.47Comparators: 27.61 Mean TC, mg/dL: Cases: 211.85Comparators: 214.69 Female: Case: 50.82%Comparators: 57.06% White: Case: 68.1%Comparators: 73.38% HT:Cases: 44.54 %Comparators: 32.80 % Diabetes:Cases: 13.98%Comparators: 10.76% Smoking:Cases: 25.73%Comparators: 25.83% Mean age, year: Cases: 68.3 ± 9.2 Comparators: 64.3 ± 9.3 Mean BMI, kg/m2:Cases: 29.2 ± 6.1Comparators: 29.3 ± 6.2 Mean SBP, mmHg:Cases: 130.1 ± 16.9 Comparators: 126.9 ± 16.4 Female:Cases: 45.4%Comparators: 59% Black: Cases: 41.9%Comparators: 39.9% EducationNo high school:Cases: 15.5%Comparators: 11.1% High school/no college:Cases: 26.3%Comparators: 25.6% College or professional: Cases: 58.2%Comparators: 63.3% Geographic regionNon-Belt:Cases: 47.2%Comparators: 43.9% Belt:Cases: 33.9%Comparators: 34.8% Buckle:Cases: 19.0%Comparators: 21.3% Previous heart disease: Cases: 25.4%Comparators: 12.2% HT:Cases: 64.7%Comparators: 56.2% DM: Cases: 21.8%Comparators: 19.1% AF: Cases: 9.7%Comparators: 7.8% LVH: Cases: 11.2%Comparators: 9.4% Current smoking:Cases: 13.0%Comparators: 14.0% Use of warfarin: Case: 3.5%Comparators: 2.7% Use of aspirin: Case: 48.1%Comparators: 40.9%Mean age, year: Cases: 58.7 ± 19.3 (Uniform PVCs), 65.7 ± 16.9 (Multiform PVCs)Comparators: 50.7 ± 20.1 Female:Cases: 44.9% (Uniform PVCs), 31.4% (Multiform PVCs)Comparators: 53.4% DM: Cases: 7.4% (Uniform PVCs), 9.4% (Multiform PVCs)Comparators: 5.6% HT: Cases: 31.2% (Uniform PVCs), 38.0% (Multiform PVCs)Comparators: 21.6% Hyperlipidemia: Cases: 7.4% (Uniform PVCs), 5.8% (Multiform PVCs)Comparators: 5.5% CKD: Cases: 1.4% (Uniform PVCs), 1.4% (Multiform PVCs)Comparators: 0.3% Cirrhosis: Cases: 0.8% (Uniform PVCs),0.8% (Multiform PVCs)Comparators: 0.5% AF: Cases: 6.7 % (Uniform PVCs), 6.8 % (Multiform PVCs)Comparators: 6.7% CLD: Cases: 2.6% (Uniform PVCs), 2.8% (Multiform PVCs)Comparators: 2.0% Use of AAD: Cases: 0.2% (Uniform PVCs), 0.5% (Multiform PVCs)Comparators: 0.5% Use of anti-HT: Cases: 16.4% (Uniform PVCs), 20.8 % (Multiform PVCs)Comparators: 12.2% Use of statin: Cases: 7.2 % (Uniform PVCs), 5.7% (Multiform PVCs)Comparators: 5.1% Mean age, year:Cases: 61.0 ± 15.2Comparators: 57.6 ± 16.4 Female: Cases: 56.7 %Comparators: 52.7% DM:Cases: 17.5 %Comparators: 20.0% HT:Cases: 28.4%Comparators: 30.6% CAD: Cases: 11.3%Comparators: 12.4% MedicationAmiodarone: Cases: 7.7%Comparators: 0% Propafenone: Cases: 1.0%Comparators: 0% Digoxin: Cases: 5.2%Comparators: 4.8% Beta-blocker:Cases: 53.6%Comparators: 8.2% CCB: Cases: 21.6%Comparators: 20% ARB & ACEI: Cases: 17.0%Comparators: 16.4% Statin: Cases: 39.4%Comparators: 37.6% Aspirin: Cases: 24.6%Comparators: 25.3% Clopidogrel: Cases: 13.4%Comparators: 12.0% VKA: Cases: 9.8%Comparators: 11.2%Diagnosis of PVCsPVCs were detected by 2-minute ECG.PVCs were detected by routine ECG. PVCs were detected by 24-hour Holter monitoring.PVCs were detected by standard ECG or 24-hour Holter monitoring.Diagnosis of strokeThe diagnosis of ischemic stroke was supported by annual telephone follow-up and a community surveillance system. Stroke was diagnosed by agreement of computer and reviewer classification. Disagreements were adjudicated by a second physician-reviewer.The diagnosis of ischemic stroke was supported by telephone follow-up every 6 months. Stroke events were defined following the WHO definition. The stroke was diagnosed and confirmed by an adjudication committee.Ischemic stroke was diagnosed by physicians and also confirmed by brain imaging.Ischemic stroke was determined by a neurologist if the patient felt painless, weakness, sudden numbness or dead feeling on one side of the body, sudden painless loss of vision, and sudden loss of ability to understand what people were saying and also confirmed by brain MRI in all patients.Confounder adjusted in the multivariate analysisAge, race, gender, BMI, HT, diabetes, smoking, TC levelsAge, sex, race, geographic region, education level, previous heart disease, SBP, use of antihypertensive medication, LVH, AF, DM, current smoking, use of warfarin and aspirinAge, sex, HT, DM, CKD, use of hypertensive medicationAge, AF, HT, LVH, E/E’, MR grade, NT-proBNPNewcastle-Ottawa scoreSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsSelection: 3 stars Comparability: 1 star Outcome: 3 starsSelection: 4 stars Comparability: 2 stars Outcome: 3 starsBaseline characteristics of studies included in the meta-analysisAbstract Figure. Forest plot of the meta-analysis

Background Matched donor (MD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the preferred choice of treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) patients who have achieved complete remission. This systematic review and meta-analysis was conducted to investigate the effects of allo-HSCTs from different donor types for Ph+ ALL patients who received tyrosine kinase inhibitors (TKIs). Methods Studies in EMBASE and MEDLINE between inception and December 2020 were identified using search terms related to "Ph+ ALL" and "HSCT." Eligible studies were studies with Ph+ ALL patients who received a TKI and allo-HSCT. The primary outcomes of interest-the overall survival (OS) or relapse-free survival (RFS)-needed to be reported. The Mantel-Haenszel method was used to combine the effect estimates and associated 95% confidence intervals (CIs) of each donor type. Results Fourteen cohort studies were identified for the meta-analysis. Haploidentical (HID)-HSCT for Ph+ ALL patients resulted in a superior RFS to MD-HSCT, with a pooled odds ratio (OR) of 1.57 (95% CI, 1.05-2.32; I2 = 0%). However, HID-HSCT and MD-HSCT had comparable OS. Furthermore, HID-HSCT group had a significantly lower relapse rate than MD-HSCT group. On the other hand, the risks of graft-versus-host disease (GvHD) were higher for HID-HSCT and pooled OR of chronic GvHD rate. The OS and RFS of matched sibling-HSCT, matched unrelated-HSCT, and cord blood-HSCT were comparable with those of HID-HSCT. Conclusion This systematic review and meta-analysis showed that HID-HSCT is as effective as MD-HSCT in Ph+ ALL patients.

Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40–60 ng/mL (100–150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

BACKGROUND/AIM To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS Twenty adults with vitamin D insufficiency/deficiency [25(OH)D

Vitamin D plays an essential role in regulating calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. Humans obtain vitamin D from sunlight exposure, dietary foods and supplements. There are two forms of vitamin D: vitamin D(3) and vitamin D(2). Vitamin D(3) is synthesized endogenously in the skin and found naturally in oily fish and cod liver oil. Vitamin D(2) is synthesized from ergosterol and found in yeast and mushrooms. Once vitamin D enters the circulation it is converted by 25-hydroxylase in the liver to 25-hydroxyvitamin D [25(OH)D], which is further converted by the 25-hydroxyvitamin D-1α-hydroxylase in the kidneys to the active form, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. 1,25(OH)(2)D binds to its nuclear vitamin D receptor to exert its physiologic functions. These functions include: promotion of intestinal calcium and phosphate absorption, renal tubular calcium reabsorption, and calcium mobilization from bone. The Endocrine Society's Clinical Practice Guideline defines vitamin D deficiency, insufficiency, and sufficiency as serum concentrations of 25(OH)D of

Background: Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of vitamin-D-related genetic variations with nonalcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using a search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible studies must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3495 articles were identified. After a systematic review, twelve studies were included. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indicating the role of vitamin D in the pathogenesis of NAFLD.

There is a bidirectional association between hyperglycemia (HG) and COVID-19 severity. We conducted a retrospective cohort study in COVID-19 patients aged ≥18 years hospitalized at the Boston Medical Center during March 1 - August 4, 2020 with the aim to determine the relationships among HG, presence of type 2 diabetes (T2D) and outcomes of COVID-19. Blood glucose levels (BG) measured on admission were extracted from the hospital database. HG was defined as BG >200 mg/dL. Patients with type 1 diabetes or BG Disclosure N. Charoenngam: None. M. F. Holick: Consultant; Self; Biogena Inc, Ontometrics Inc, Other Relationship; Self; Quest Diagnostics, Speaker’s Bureau; Self; Abbott. C. Apovian: Board Member; Self; Abbott, Allergan plc, Gelesis, Novo Nordisk, Nutrisystem, Tivity Health, Xeno Bioscience, Zafgen, Inc. Funding National Institutes of Health (2T32DK7201-42 to N.C.), (P30DK046200 to C.A.)

Background Black individuals have been disproportionately affected by the coronavirus disease 2019 (COVID-19). However, it remains unclear whether there are any biological factors that predispose Black patients to COVID-19-related morbidity and mortality. Objective To compare in-hospital morbidity, mortality, and inflammatory marker levels between Black and White hospitalized COVID-19 patients. Design and Participants This single-center retrospective cohort study analyzed data for Black and White patients aged ≥18 years hospitalized with a positive SARS-CoV-2 PCR test between March 1, 2020, and August 4, 2020. Main Measures The exposure was self-identified race documented in the medical record. The primary outcome of was in-hospital death. Secondary outcomes included intensive care unit admission, hospital morbidities, and inflammatory marker levels. Key Results A total of 1,424 Black and White patients were identified. The mean ± SD age was 56.1 ± 17.4 years, and 663 (44.5%) were female. There were 683 (48.0%) Black and 741 (52.0%) White patients. In the univariate analysis, Black patients had longer hospital stays (8.1 ± 10.2 vs. 6.7 ± 8.3 days, p = 0.011) and tended to have higher rates of in-hospital death (11.0% vs. 7.3%), myocardial infarction (6.9% vs. 4.5%), pulmonary embolism (PE; 5.0% vs. 2.3%), and acute kidney injury (AKI; 39.4% vs. 23.1%) than White patients (p

Vitamin D is known not only for its importance for bone health but also for its biologic activities on many other organ systems. This is due to the presence of the vitamin D receptor in various types of cells and tissues, including the skin, skeletal muscle, adipose tissue, endocrine pancreas, immune cells, and blood vessels. Experimental studies have shown that vitamin D exerts several actions that are thought to be protective against coronavirus disease (COVID-19) infectivity and severity. These include the immunomodulatory effects on the innate and adaptive immune systems, the regulatory effects on the renin-angiotensin-aldosterone-system in the kidneys and the lungs, and the protective effects against endothelial dysfunction and thrombosis. Prior to the COVID-19 pandemic, studies have shown that vitamin D supplementation is beneficial in protecting against risk of acquiring acute respiratory viral infection and may improve outcomes in sepsis and critically ill patients. There are a growing number of data connecting COVID-19 infectivity and severity with vitamin D status, suggesting a potential benefit of vitamin D supplementation for primary prevention or as an adjunctive treatment of COVID-19. Although the results from most ongoing randomized clinical trials aiming to prove the benefit of vitamin D supplementation for these purposes are still pending, there is no downside to increasing vitamin D intake and having sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at a level of least 30 ng/mL (75 nmol/L) and preferably 40 to 60 ng/mL (100-150 nmol/L) to minimize the risk of COVID-19 infection and its severity.

Background and objectives Little is known about atrial involvement in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Recent studies have suggested that atrial arrhythmia (AA), including atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), was common among these patients although the reported prevalence varied considerably across the studies. Methods We searched for published articles indexed in MEDLINE and EMBASE databases from inception through Sep 22, 2019 to identify cohort studies of patients with ARVC that described the prevalence of atrial arrhythmia among the participants. The pooled prevalence across studies was calculated. Results A total of 16 cohort studies with 1,986 patients with ARVC were included into this meta-analysis. The pooled prevalence of overall AA among patients with ARVC was 17.9% (95% CI, 13.0%–24.0%; I2 88%), the pooled prevalence of AF of 12.9% (95% CI, 9.6%–17.0%; I2 78%), the pooled prevalence of AFL of 5.9% (95% CI, 3.7%–9.2%; I2 70%), and the pooled prevalence of AT of 7.1% (95% CI, 3.7%–13.0%; I2 49%). Conclusions AA is common among patient with ARVC with the pooled prevalence of approximately 18%, which is substantially higher than the reported prevalence of AA in general population. Funding Acknowledgement Type of funding source: None

Background. Little is known about the association among skin color, sunlight exposure. and vitamin D status in Southeast Asian population. Objective. To investigate the association between skin color measured by von Luschan chromatic scale (VLCS) and vitamin D status in Thai medical ambulatory patients. Methods. Medical ambulatory patients were enrolled. The eligibility criteria were as follows: aged >18 years, stable medical conditions, and no conditions directly affecting vitamin D status. Serum 25-hydroxyvitamin D [25(OH)D] levels were assessed. Skin color at the outer forearm was assessed using VLCS which grades skin color from the lightest score of 1 to the darkest score of 36. Patients were systematically interviewed to estimate daily sunlight exposure time. Results. A total of 334 patients were enrolled. Data were expressed as mean ± SD. The mean serum 25(OH)D was 25.21 ± 10.06 ng/mL. There were 17 (5.1%), 217 (65.0%), and 100 (29.9%) patients who had light brown (VLCS score 18–20), medium brown (VLCS score 21–24), and dark brown (VLCS score 25–27) skin colors, respectively. The mean serum 25(OH)D level was higher in patients with dark brown skin than in patients with medium brown and light brown skin (28.31 ± 10.34 vs. 24.28 ± 9.57 and 19.43 ± 9.92 ng/mL, respectively, both p < 0.05 ). Multivariate analysis showed that darker skin color and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency (dark brown vs. light brown: odds ratio, 0.263, 95% CI: 0.081–0.851, p = 0.026 ; medium brown vs. light brown: odds ratio, 0.369, 95% CI: 0.987–1.003, p = 0.067 ; sunlight exposure time odds ratio per 1 minute/day increase 0.955, 95% CI: 0.991–1.000, p = 0.037 ), after adjusting for possible confounders. Conclusions. We found that darker skin color at sunlight exposure area and increased sunlight exposure time were independently associated with decreased odds of vitamin D deficiency in Thai medical ambulatory patients.

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve the optimal overall health benefits of vitamin D.

This study aimed to determine factors influencing happiness in preclinical students especially in aspects of teaching and learning, students’ motivation, study habits, and academic achievement. This study was a questionnaire-based cross-sectional study. The questionnaire was validated and approved for clarity, readability, rational analysis, and comprehensiveness by the experts. Questionnaires were sent to all second and/or third-year medical students of the 2018 (328) and 2019 (329) classes, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand. Cronbach’s alpha values were 0.886. The data were analyzed by the Statistical Package for Social Science version 18. From open-ended questions, the top 5 ranking factors increasing students’ happiness were teaching of instructors, content satisfaction, content understanding, free time, and handouts. Factors that had positive influences/associations with happiness of preclinical students were happiness in learning subjects taught in a particular year; satisfaction of content, study outcomes, materials, handouts, teaching motivating desire to learn, and applicability of content to medical profession; high motivation to study medicine, expected score, and the percentage of achievement of study targets; less amount of time spent on recorded-e-lecture study and internet for non-academic use; and low stress. Happiness of preclinical students was influenced by satisfaction in teaching and learning, their attitude, study habits, and academic achievement. Further studies on determining students’ happiness after improvement of teaching and learning environments, augmenting activities that enhance students’ motivation, and promoting good study habits among medical students, are required to prove whether enhancement of these factors could effectively increase students' happiness.

Background/aim To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. Results There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. Conclusion These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.

Several studies have shown high prevalence of low serum 25-hydroxyvitamin D (25OHD) level in severe chronic kidney disease (CKD). However, studies on vitamin D status in patients with mild to moderate kidney impairment such as stages 1 to 3b CKD are limited. This cross-sectional study aimed to examine vitamin D status in doing-well ambulatory patients with stable medical conditions who had mild to moderate kidney impairment defined by estimated glomerular filtration rate (eGFR) of >30 mL/min/1.73m2. All patients had no conditions known to affect vitamin D status including vitamin D supplementation and were assessed for renal function, 25OHD, and parathyroid hormone (PTH) levels. Data are expressed as mean ± SD (range) or % as appropriate. There were 333 patients with a mean age of 64.5 ± 10.3 years old (26 - 88), 67.9% were elderly (aged >60), and 63.7% were female. The patients’ major underlying diseases included type 2 diabetes mellitus (71.5%), hypertension (69.1%), dyslipidemia (82.8%), and coronary artery disease (6.9%). Mean serum 25OHD was 25.1 ± 10.1 ng/mL (3.0 - 70.0). 42.1%, 29.7% and 2.7 % of the patients had 25OHD of 20 - 60), the prevalence of 25OHD of 20

Background Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone–all in combination with TKIs in adult Ph+ ALL patients. Materials and methods This systematic review identified studies from the EMBASE and MEDLINE databases from inception to April 2021 using search terms related to “ALL” and “HSCT.” Eligible studies could be randomized controlled trials or cohort studies that included adult Ph+ ALL patients who received a TKI and either allo-HSCT, auto-HSCT, or CMT alone, and that reported the number of patients in each group for each of our primary outcomes of interest: overall survival (OS) or disease-free survival (DFS). Point estimates and associated 95% confidence intervals (CI) from each study were combined using the Hantel-Maenszel method. Results After two rounds of review, 26 cohort studies were determined to be eligible for the meta-analysis. Adult Ph+ ALL patients who received HSCT had better survival outcomes than those who did not receive any HSCT (pooled odds ratio [OR] for OS of 1.61, 95%CI: 1.08–2.40; I2 = 59%, and for DFS of 3.23, 95%CI: 2.00–5.23; I2 = 62% for allo-HSCT; and, pooled OR for OS of 7.04, 95%CI: 1.97–25.15; I2 = 0%, and for DFS of 5.78, 95%CI: 1.04–32.19; I2 = 42% for auto-HSCT). Allo-HSCT recipients had comparable OS and DFS, but lower relapse rate compared to auto-HSCT recipients. Funnel plot generally demonstrated no presence of publication bias. Conclusions This systematic review and meta-analysis demonstrated superior results of HSCT in Ph+ ALL patients compared to CMT alone. Moreover, auto-HSCT could be implemented with comparable survival outcomes to allo-HSCT in patients with no available donor or when haploidentical HSCT is not feasible.

This study aimed to determine the relationships among hyperglycemia (HG), the presence of type 2 diabetes (T2D), and the outcomes of COVID-19. Demographic data, blood glucose levels (BG) measured on admission, and hospital outcomes of COVID-19 patients hospitalized at Boston University Medical Center from 1 March to 4 August 2020 were extracted from the hospital database. HG was defined as BG &gt, 200 mg/dL. Patients with type 1 diabetes or BG &lt, 70 mg/dL were excluded. A total of 458 patients with T2D and 976 patients without T2D were included in the study. The mean ± SD age was 56 ± 17 years and 642 (45%) were female. HG occurred in 193 (42%) and 42 (4%) of patients with and without T2D, respectively. Overall, the in-hospital mortality rate was 9%. Among patients without T2D, HG was statistically significantly associated with mortality, ICU admission, intubation, acute kidney injury, and severe sepsis/septic shock, after adjusting for potential confounders (p &lt, 0.05). However, only ICU admission and acute kidney injury were associated with HG among patients with T2D (p &lt, 0.05). Among the 235 patients with HG, the presence of T2D was associated with decreased odds of mortality, ICU admission, intubation, and severe sepsis/septic shock, after adjusting for potential confounders, including BG (p &lt, 0.05). In conclusion, HG in the subset of patients without T2D could be a strong indicator of high inflammatory burden, leading to a higher risk of severe COVID-19.

Context: Previous studies on the association between atopic dermatitis (AD) and systemic lupus erythematosus (SLE) have yielded inconsistent results. Aims: To investigate the relationship between atopic dermatitis and systemic lupus erythematosus. Settings and Design: Systematic review and meta-analysis. Materials and Methods: A systematic review was conducted on EMBASE and MEDLINE databases from inception to March 2020 using a search strategy that consisted of terms related to AD and SLE. Eligible study must be either cohort or case-control study. For cohort studies, they must include patients with AD and comparators without AD, then follow them for incident SLE. For case-control studies, they must include cases with SLE and controls without SLE and examine their prior history of AD. Statistical Analysis Used: Meta-analysis of the studies was performed using a random-effect, generic inverse variance method to combine effect estimate and standard error. Funnel plot was used to assess publication bias. Results: A total of 21,486 articles were retrieved. After two rounds of review by three investigators, six case-control studies were qualified for the meta-analysis. The case-control study meta-analysis found a significantly increased odds of SLE among patients with AD with the pooled odds ratio of 1.46 (95% CI, 1.05–2.04). Conclusions: A significant association between AD and increased odds of SLE was observed by this systematic review and meta-analysis.

Academic achievement is a major concern of preclinical students. This study aimed to determine factors influencing academic achievement in preclinical years. Questionnaires were sent to all students of the 2019 class at the 1st (2019/1) and 2nd preclinical years (2019/2) and the 2018 class at the 2nd preclinical year (2018/2) without sampling, with 85.11% (280/328), 86.32% (284/328), and 83.54% (274/328) being returned, respectively. Students were divided into Q1 (lowest)-Q2-Q3-Q4 (highest) according to quartiles of their GPA. Q4 students had higher examination expectation and achievement of study targets in all classes and more time spent on non-recorded-e-lecture study in the 2018/2 and 2019/2 classes; but lower time spent on recorded-e-lecture study in the 2019/1 class and non-academic-internet use in the 2019/2 and 2018/2 classes than other groups. In contrast, Q1 students had higher instances of lateness and absence/year in the 2019/2 and 2018/2 classes but lower happiness scores in the 2018/2 class compared to other groups. Obese and overweight students had significantly lower GPA than normal weight and underweight students of the 2019/2 class (p

An early clinical exposure project conducted by clinical students aimed to promote direct clinical experience to preclinical students. The aim of this study was to determine the effects of the project on academic achievement and study attitudes and habits between participating and nonparticipating students before ( test 1) and after the project ( test 2) in the second preclinical year and at the end of the first semester of the first clinical year ( test 3), with a subgroup analysis of the first (lowest) to third (highest) tertile of the score. Questionnaires were sent to the first clinical year students at test 3 and asked the information retrospectively at test 1 and test 2 in second year preclinical and currently at test 3, with 83.86% (265/316) being returned. Mean percentile of scores was higher at test 2 compared with test 1 in the first tertile group of participating students. Motivation to study medicine (motivation), realization of application of preclinical knowledge to clinical study (application), understanding of clinical environment (environment), and lesson review after class (review) were higher for participating than nonparticipating students at test 2 and/or test 3. Searching additional study information was higher at test 2 compared with test 1 only for participating students. This project could effectively promote application, motivation, environment, and review for participating vs. nonparticipating students at test 2 and/or test 3. Effortless, intimate, and effective communication between clinical and preclinical students and a direct experience in early clinical exposure might be key success factors.

In the case reported by Auguste and colleagues, [1][1] we believe that the patient experienced vitamin D intoxication because of an underlying pathologic condition that the authors failed to recognize. The authors incorrectly concluded that a dose of 8000–12 000 IU daily can result in vitamin D