A Novel De Novo Frameshift Pathogenic Variant in the FAM111B Resulting in Progressive Osseous Heteroplasia Phenotype.

INTRODUCTION: Progressive osseous heteroplasia (POH) is a rare, debilitating disorder characterized by heterotopic ossification in the skin and muscles, resulting in contractures of the joints and progressive loss of function. While 60-70% of the POH patients have paternally inherited, inactivating pathogenic variants in GNAS, the remaining 30-40% have no known etiology. FAM111B pathogenic variants, located on chromosome 11q12.1, cause POIKTMP (hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis), a very rare, autosomal-dominant disorder with high frequency of de novo missense pathogenic variants, which affects multiple tissues and organs, causing extensive fibrosis and muscle adiposis, though the exact mechanism is unknown. To our knowledge, there are no reports of FAM111B associated with POH. We describe the first case of POH phenotype associated with a novel de novo frameshift pathogenic variant in the FAM111B and present an analysis of the protein structure and function caused by this genomic disruption. CASE: A 15-year-old African-American male presented with generalized calcific nodules, progressive contractures, and muscle weakness leading to immobility, beginning at 6 years of age. Cutaneous examination showed generalized hard nodules varying from small to plaque-like ulcerated erupted skin lesions. Biochemical evaluation revealed 25(OH) vitamin D insufficiency (20 ng/mL), and normal levels of parathyroid hormone, FGF-23, alkaline phosphatase, calcium, and phosphorus. Skeletal survey radiographs and computed tomography (CT) of the chest, abdomen, and pelvis showed extensive soft tissue and muscle heterotopic ossifications involving shoulders, axillae, trunk, abdomen, pelvis, upper and lower extremities, in a clumped, conglomerate distribution within muscle, subcutaneous fat, and in some areas extending to the skin. There was no pulmonary fibrosis on the chest CT. The clinical and radiographic findings were most consistent with POH. A trio-clinical exome sequencing revealed a de novo heterozygous likely pathogenic variant in the FAM111B (OMIM # 615584) (c.1462delT [p.Cys488Valfs*21]). The resulted frameshift change in exon 4 replaced C-terminal region with 21 alternative amino acids. Multiple, previously reported disease-associated variants appear to localize within the trypsin-like cysteine/serine peptidase domain in which this variant occurs, supporting the functional significance of this region, though none have been previously reported to be associated with POH phenotype. Our 3D protein modeling showed obliteration of predicted protein folding and structure, and elimination of the zinc-binding domain, likely severely affecting protein function. CONCLUSION: This is the first case of POH phenotype associated with a novel de novo pathogenic frameshift variant in FAM111B. Whether the frameshift change in FAM111B predicts POH remains unclear. Further evaluations are necessary to fully elucidate this finding and the potential role and mechanism by which the FAM111B variants contributes to POH phenotype.

Telomere shortening correlates with disease severity in hemoglobin H disease patients.

Hemoglobin H (Hb H) disease is the most significant health problem of the α-thalassemia syndromes. The Hb disease patients are categorized based on their genotype to deletional and nondeletional, with the latter genotype presents the more severe clinical symptoms. Since telomere length is an indicator of biological aging and health, we hypothesized that telomere length could reflect Hb H disease's severity. In this study, we recruited 48 deletional and 47 nondeletional Hb H disease patients, along with 109 normal controls, for telomere length assessment. The leukocyte telomere length was assessed by monochromatic multiplex real-time PCR and reported as the telomere to single-copy gene (T/S) ratio. When telomere length was adjusted for age, the analysis of covariance between the control and the two Hb H disease groups revealed no significant difference. However, the telomere shortening rate was more rapid in the nondeletional Hb H disease group than those of the control and deletional Hb H disease groups. Gender analysis found that male patients have a significantly lower T/S ratio than females in the nondeletional group but not in the control and deletional groups. In the two disease groups, the T/S ratio was not influenced by ferritin level or transfusion burden but was positively correlated with the absolute reticulocyte count.

Smoking & risk of advanced liver fibrosis among patients with primary biliary cholangitis: A systematic review & meta-analysis.

Background & objectives: Studies have suggested that smoking may accelerate the progression of fibrosis among patients with primary biliary cholangitis (PBC), although the data are limited. The current review was undertaken with the aim to comprehensively analyze this possible association by identifying all relevant studies and summarizing their results. Methods: A comprehensive literature review on MEDLINE and EMBASE databases was performed from inception through February 2019 to identify all relevant studies. Eligible studies included cross-sectional studies that recruited patients with PBC and collected data on the smoking status and presence or absence of advanced liver fibrosis for each participant. Odds ratios (OR) with 95 per cent confidence intervals (CI) was desirable for inclusion or sufficient raw data to calculate the same for this association. Adjusted point estimates from each study were extracted and combined together using the generic inverse variance method of DerSimonian and Laird. I2 statistic, which quantifies the proportion of total variation across studies was used to determine the between-study heterogeneity. Results: Three cross-sectional studies with 544 participants were included. The pooled analysis found a significantly increased risk of advanced liver fibrosis among patients with PBC who were ever-smokers compared to those who were nonsmokers with the pooled OR of 3.00 (95% CI, 1.18-7.65). Statistical heterogeneity was high with I2 of 89 per cent. Interpretation & conclusions: This meta-analysis found that smoking is associated with a significantly higher risk of advanced liver fibrosis among patients with PBC. Further prospective studies are still required to determine whether this association is causal.

Obesity and Risk of Small Intestine Bacterial Overgrowth: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Recent studies have proposed that obesity may be associated with a higher risk of small intestine bacterial overgrowth (SIBO) although the results were inconsistent. The microbiome has a known metabolic role; its impact on obesity in animal models generated the hypothesis of an association between a dysfunctional microbiome and obesity. We performed this systematic review and meta-analysis to elucidate this possible association by summarizing all available data. METHODS: A literature search utilizing MEDLINE and EMBASE databases from inception until August 2019 was conducted. Eligible studies included either cohort studies or cross-sectional studies that consisted of two groups of participants, those with obesity and those without obesity, and compared the prevalence of SIBO between the groups. Adjusted odds ratios (OR) from each study were consolidated by the generic inverse variance method of DerSimonian and Laird. RESULTS: A total of five studies with 515 patients fulfilled eligibility criteria and were included in this meta-analysis. The risk of SIBO among individuals with obesity was higher than in individuals without obesity but did not reach statistical significance with a pooled OR of 2.08 [95% confidence interval (CI) 0.82-5.31; p = 0.12; I2 84%]. Sensitivity analysis including only studies from Western countries increased the pooled OR to 3.41 and reached statistical significance (95% CI 1.21-9.59; p = 0.02; I2 62%). CONCLUSIONS: This meta-analysis found that the risk of SIBO was about two times higher among individuals with obesity compared to individuals without obesity, although the result did not reach statistical significance. The risk increased to threefold and reached statistical significance when only studies from Western countries were included. These observations may suggest the role of obesity as a predisposing factor for SIBO although more studies are still needed to corroborate these preliminary results.

Association between sarcopenia and hepatic encephalopathy: A systematic review and meta-analysis.

Studies have suggested that the presence of sarcopenia in patients with cirrhosis could be a predisposing risk factor for hepatic encephalopathy. This systematic review and meta-analysis were conducted to summarize all available evidence on this relationship. A systematic review was carried out in Medline and EMBASE database through December 2018 to identify studies that recruited patients with cirrhosis from any causes and collected data on the presence of minimal or overt hepatic encephalopathy as well as sarcopenia. All study designs (case-control, cohort and cross-sectional studies) were eligible for the meta-analysis. Odds ratio (OR) and 95% confidence interval (CI) were extracted from the included studies and were pooled together using random-effect, generic inverse variance method of DerSimonian and Laird. Five cross-sectional studies with a total of 1,713 patients met our eligibility criteria and were included into the meta-analysis. We found a significantly higher risk of both mild and overt hepatic encephalopathy among cirrhotic patients with sarcopenia when compared with cirrhotic patients without sarcopenia with the pooled OR of 3.34 (95% CI: 1.68-6.67; I2=37%) and 2.05 (95% CI: 1.28-3.29; I2=61%), respectively. This systematic review and meta-analysis demonstrated a significant association between sarcopenia and hepatic encephalopathy among patients with cirrhosis.

Statins & risk of Clostridium difficile infection: A meta-analysis.

Background & objectives: Clostridium difficile infection is one of the most common healthcare-associated infections worldwide. Recent epidemiologic studies have suggested that statin users may have a lower risk of C. difficile infection, although the results are inconsistent. This meta-analysis was conducted with the aim of summarizing all available data to assess the risk of C. difficile infection among statin users versus non-users. Methods: A literature review was performed using the MEDLINE and EMBASE databases from inception to October 2017. Cohort, case-control and cross-sectional studies that compared the risk of C. difficile infection among statin users versus non-users were included. Pooled odds ratio (OR) and 95 per cent confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Six case-control studies and two cross-sectional studies met the eligibility criteria and were included in this meta-analysis. The risk of C. difficile infection among statin users was significantly lower than non-users with the pooled OR of 0.74 (95% CI, 0.61-0.89). The statistical heterogeneity of this study was high (I[2]=90%). Interpretation & conclusions: This meta-analysis demonstrated a decreased risk of C. difficile infection among statin users versus non-users. Further studies are required to clarify the role of statins for prevention of C. difficile infection in clinical practice.

Helicobacter pylori and Risk of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Patients with H. pylori infection may be at an increased risk of nonalcoholic fatty liver disease (NAFLD) because of chronic inflammation and insulin resistance. Several epidemiologic studies attempting to determine this risk have yielded inconsistent results. This meta-analysis was conducted with the aims to summarize all available evidence and estimate the risk of NAFLD in patients with H. pylori infection. METHODS: A literature search was performed using MEDLINE and EMBASE database from inception to June 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of NAFLD among patients with H. pylori infection versus without H. pylori infection were included. Pooled odds ratios and 95% confidence intervals were calculated using a random-effect, generic inverse variance method. RESULTS: Six studies met our eligibility criteria and were included in this analysis. We found a statistically significant increased risk of NAFLD among patients with H. pylori infection with the pooled odds ratios of 1.21 (95% confidence interval, 1.07-1.37). The statistical heterogeneity was low with an I of 49%. CONCLUSIONS: A significantly increased risk of NAFLD among patients with H. pylori infection was demonstrated in this meta-analysis. Further studies are required to clarify how this risk should be addressed in clinical practice.

Heavy Coffee Consumption and Risk of Pancreatitis: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Heavy consumption of coffee may have a protective effect against pancreatitis although results from previous studies were inconsistent. This meta-analysis was conducted with the aim to summarize all available data. METHODS: This meta-analysis included observational studies that compared the risk of pancreatitis between heavy coffee-drinkers and individuals who were not heavy coffee-drinkers. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Out of 219 retrieved articles, four studies with 351,137 participants met the eligibility criteria and were included in the analysis. The risk of pancreatitis among heavy coffee-drinkers was significantly lower than individuals who were not heavy coffee-drinkers with the pooled RR of 0.78 (95% CI 0.67-0.91). The statistical heterogeneity between the studies was insignificant (I2 = 0%). CONCLUSIONS: This meta-analysis demonstrated a significantly decreased risk of pancreatitis among heavy coffee-drinkers. However, further investigations are still required to determine causality and potential clinical application.

Hyperuricaemia and risk of nonalcoholic fatty liver disease: A meta-analysis.

BACKGROUND: The association between hyperuricaemia and nonalcoholic fatty liver disease (NAFLD), one of the leading causes of cirrhosis worldwide, has been demonstrated in recent epidemiological studies. This meta-analysis was conducted to summarize all available data and to estimate the risk of NAFLD among subjects with hyperuricaemia. METHODS: Comprehensive literature review was conducted using MEDLINE and EMBASE database through August 2016 to identify studies that compared the risk of NAFLD among subjects with hyperuricaemia vs those with normal uric acid level. Effect estimates from individual study were extracted and combined together using random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Twenty-five studies met the eligibility criteria and were included in the meta-analysis. The risk of NAFLD in subjects with hyperuricaemia was significantly higher than subjects with normal uric acid level with the pooled odds ratio (OR) of 1.97 (95% confidence interval (CI), 1.69-2.29). The heterogeneity between studies of the overall analysis was high with an I2 of 87%. Subgroup analysis based on 11 studies that provided data on males subgroup and nine studies that provided data on females subgroup showed that the risk was significantly increased for both sexes with pooled OR of 1.64 (95% CI, 1.40-1.93) among males and pooled OR of 2.21 (95% CI, 1.85-2.64) among females. CONCLUSIONS: A significantly increased risk of NAFLD among patients with hyperuricaemia was demonstrated in this meta-analysis. Further studies are required to establish the role of uric acid in the pathogenesis of NAFLD.

Association between coffee consumption and risk of renal cell carcinoma: a meta-analysis.

BACKGROUND/OBJECTIVES: The risk of renal cell carcinoma (RCC) in individuals who regularly drink coffee is controversial. Several antioxidant compounds in coffee have been proposed to reduce the risk of RCC, while the findings from several studies raise concerns regarding a potential increased risk of RCC with coffee consumption. AIM: This meta-analysis aims to evaluate the association between coffee consumption and RCC. METHODS: A literature search was performed using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews from inception until December 2016. Studies that reported odd ratios or hazard ratios comparing the risk of RCC in individuals who consumed a significant amount of coffee (at least one cup of coffee per day) versus those who did not consume coffee were included. Pooled risk ratios (RR) and 95% confidence intervals (CI) were computed using a random-effect, generic inverse variance method. RESULTS: Twenty-two observational studies (16 case-control and 6 cohort studies) were included in our analysis to assess the association between RCC and coffee consumption. The pooled RR of RCC in individuals consuming coffee was 0.99 (95% CI, 0.89-1.11). Subgroup analyses stratified by gender showed pooled RRs of RCC of 1.15 (95% CI, 0.85-1.55) in females and 0.87 (95% CI, 0.72-1.04) in males. CONCLUSIONS: Our study demonstrates no significant association between coffee consumption and RCC. Thus, coffee consumption is likely not a risk factor for RCC. Whether coffee consumption has a potential role in reduced risk of RCC, particularly in men, requires further investigations.

Hepatitis C Virus Infection and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVES: Hepatitis C virus (HCV) infection is one of the leading causes of cirrhosis. As a result of chronic inflammatory response to the virus, HCV-infected patients may be at a higher risk of venous thromboembolism (VTE). However, the data on this association is unclear. This systematic review and meta-analysis was conducted with the aims to summarize all available evidence. MATERIAL AND METHODS: A literature search was performed using MEDLINE and EMBASE from inception to April 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of VTE among HCV-infected patients vs. subjects without HCV infection were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Three studies met our eligibility criteria and were included in analysis. The pooled RR of VTE in HCV-infected patients vs. subjects without HCV infection was 1.38 (95% CI, 1.08-1.77, I2 = 40%). Subgroup analysis showed that risk was increased for both pulmonary embolism (PE) and deep venous thrombosis (DVT) even though without adequate power to demonstrate statistical significance (Pooled RR of 1.34, 95% CI, 0.67-2.66 for PE and pooled RR 1.45, 95% CI, 0.93-2.77 for DVT). CONCLUSION: Our study demonstrated a significantly increased risk of VTE among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in clinical practice.

Association of coffee consumption and chronic kidney disease: A meta-analysis.

BACKGROUND/OBJECTIVES: The risk of chronic kidney disease (CKD) in individuals who regularly drink coffee is controversial. The aim of this meta-analysis was to evaluate the association between coffee consumption and CKD. METHODS: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception until April 2016. We included studies that reported odd ratios or hazard ratios comparing the risk of CKD in individuals consuming significant amount of coffee vs. those who did not consume coffee. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: Four observational studies with 14 898 individuals were included in our analysis to assess the association between coffee consumption and CKD. Coffee consumption was defined as one cup of coffee per day or greater. The pooled RR of CKD in individuals consuming coffee was 0.71 (95% CI, 0.47-1.08). The subgroup analysis showed the pooled RRs of CKD of 1.10 (95% CI, 0.94-1.29) in males and 0.81 (95% CI, 0.58-1.13) in females, respectively. CONCLUSIONS: Our study demonstrates no significant association between coffee consumption and CKD in males. However, future studies are required to assess a potential inverse association between coffee consumption and risk for developing CKD in females.

Short sleep duration and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Several studies have suggested that short sleep duration could be a risk factor for NAFLD. However, results of those reports are inconsistent. This meta-analysis was conducted with an attempt to summarize all available data. METHODS: A comprehensive literature review was performed using MEDLINE and EMBASE database. Studies that reported relative risks, odd ratios or hazard ratios comparing the risk of NAFLD among participants who had short sleep duration versus those with longer sleep duration were included. Pooled risk ratios and 95% confidence interval were calculated using a random-effect, generic inverse variance method. RESULTS: Six studies met the eligibility criteria and were included in the meta-analysis. The risk of NAFLD in participants who had short sleep duration was significantly higher than participants with longer sleep duration with pooled risk ratios of 1.19 (95% confidence interval, 1.04-1.36, I2 = 0%). CONCLUSIONS: Our study demonstrated a small but significantly increased risk of NAFLD among participants who had short sleep duration.

Conundrum of vitamin D on glucose and fuel homeostasis.

As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date, studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D < 50 nmol/L (20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D > 75 nmol/L (30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D > 100 nmol/L (40 ng/mL). Further studies are required to confirm these observations.

Modest alcohol consumption and risk of advanced liver fibrosis in nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested an association between modest alcohol consumption and a decreased risk of advanced liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) although the results are inconsistent. The current systematic review and meta-analysis was conducted to comprehensively investigate this possible association by identifying all the relevant studies and combining their results. METHODS: A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through February 2019 to identify all cross-sectional studies that compared the prevalence of advanced liver fibrosis among NAFLD patients who were modest alcohol drinkers to NAFLD patients who were non-drinkers. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: A total of 6 studies with 8,936 participants fulfilled the eligibility criteria and were included in the meta-analysis. The risk of advanced liver fibrosis among patients with NAFLD who were modest alcohol drinkers was significantly lower compared to patients with NAFLD who were non-drinkers with a pooled odds ratio of 0.51 (95% confidence interval [CI] 0.35-0.75; I2 47%). The funnel plot was symmetric and was not suggestive of publication bias. CONCLUSION: A significantly lower risk of advanced liver fibrosis was observed among NAFLD patients who were modest alcohol drinkers compared to non-drinkers in this meta-analysis.

Hereditary hemochromatosis and risk of joint replacement surgery: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Arthritis is a known manifestation of hereditary hemochromatosis. However, whether patients with hereditary hemochromatosis have an increased risk of having joint replacement surgery compared to the general population is still unknown. This meta-analysis was conducted to better characterize this risk. METHODS: A comprehensive literature review was conducted utilizing the MEDLINE and EMBASE databases through September 2019 to identify all cohort studies that compared prevalence or incidence of joint replacement surgery (hip, ankle, or knee) between patients with hereditary hemochromatosis and individuals without hereditary hemochromatosis. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: A total of five studies with 1 293 407 participants fulfilled the eligibility criteria and were included in the meta-analysis. Overall, the risk of having joint replacement surgery was significantly increased in patients with hereditary hemochromatosis compared to individuals without hereditary hemochromatosis with the pooled relative risk (RR) of 3.32 [95% confidence interval (CI), 1.60-6.86; I 88%]. Analysis by joint found a significantly increased risk of having hip and ankle replacement surgery among patients with hereditary hemochromatosis compared with the pooled RR of 2.62 (95% CI, 2.09-3.30; I 47%) and 8.94 (95% CI, 3.85-20.78; I 14%), respectively. The risk of having knee replacement surgery was also increased but was not statistically significant (pooled RR 1.57, 95% CI, 0.83-2.98; I 66%). CONCLUSIONS: A significantly increased risk of needed joint replacement surgery among patients with hereditary hemochromatosis compared to patients without hereditary hemochromatosis was demonstrated in this study. Further studies are required to determine whether this association is causal.

COVID-19 and liver injury: a meta-analysis.

BACKGROUND/AIMS: The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury. METHODS: A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies. RESULTS: Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19. CONCLUSION: A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.

A Case of Concomitant COVID-19 Infection-Induced Acute Respiratory Distress Syndrome and Diabetic Ketoacidosis: Another Challenge in Fluid Management.

Coronavirus disease 2019 (COVID-19) has been announced as a pandemic worldwide. The respiratory tract is a target organ system, where infection can result in serious complications, like acute respiratory distress syndrome (ARDS). Management of this condition is more challenging in individuals with diabetes who developed diabetic ketoacidosis. We report a case of a 59-year-old male with type 2 diabetes who presented with productive cough, chills, and shortness of breath for four days. On examination, the patient was hypoxemic with bilateral crackles on lung auscultation. The patient's biochemistry was significant for glucose 387 mg/dL, pH 7.25, positive urine ketones, and lactic acid dehydrogenase (LDH) 325 U/L. An initial chest x-ray showed bilateral peripheral pulmonary infiltrates. The patient was subsequently intubated on the first day for worsening hypoxia due to severe ARDS. He was concomitantly treated for diabetic ketoacidosis (DKA) and hypotension with fluid resuscitation and intravenous insulin. On the same day, his hypoxia worsened with an increase in pulmonary infiltrates, so we stopped intravenous fluids and initiated norepinephrine for 24 hours. His intravenous insulin was initially started at 12 units/hour with subsequent titration down to an average of 5 units/hour. His mechanical ventilation settings followed ARDS guidelines with tidal volume 6 ml/kg based on ideal body weight. Positive COVID-19 was detected from real-time reverse transcription polymerase chain reaction (RT-PCR). After maintaining a negative fluid balance, we were able to extubate in 72 hours. DKA was resolved in 46 hours. In conclusion, type 2 diabetes is rarely affected by DKA, but can be found in up to 27% of cases. There are reports of ARDS as a serious complication in severe DKA in adults and children, yet no data for concomitant DKA and ARDS has been published. We propose that DKA management in COVID-19 patients with ARDS may be similar to the paradigm utilized for other volume restriction in patients with congestive heart failure and end-stage renal failure.

Statins and risk of peptic ulcer disease: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: Peptic ulcer disease (PUD) is one of the most common gastrointestinal disorders worldwide. Recent epidemiologic studies have suggested the protective effect of statins against the development of PUD although the results were inconsistent. This systematic review and meta-analysis was conducted with the aim to summarise all available data. METHODS: A literature review was performed using MEDLINE and EMBASE database from inception to December 2017. Cohort, case-control and cross-sectional studies that compared the risk of PUD among statins users versus non-users were included. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. RESULTS: A total of 3 studies (1 case-control and 2 retrospective cohort studies) met the eligibility criteria and were included in this meta-analysis. The risk of PUD was numerically lower among statins-users compared with non-users with the pooled OR of 0.89. However, the result did not achieve statistical significance with 95% CI of 0.67-1.18. The between-study statistical heterogeneity was high (I2 = 80%). CONCLUSIONS: This systematic review and meta-analysis found that the risk of PUD was numerically lower among statin users. However, the results did not reach statistical significance. More studies are still required to further characterise this potential protective effect.

Association between cardiac conduction defect and nonalcoholic fatty liver disease: a systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease is a common comorbidity of patients with nonalcoholic fatty liver disease (NAFLD), particularly coronary artery disease and congestive heart failure. However, the relation between NAFLD and cardiac conduction defects has not been well studied. This systematic review and meta-analysis was conducted to identify all available studies on this association and summarize their results. METHODS: A comprehensive literature review was conducted using MEDLINE and EMBASE databases through June 2020 to identify studies that compared the risk of a cardiac conduction defect among patients with NAFLD versus those without. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Three cross-sectional studies with 3651 participants fulfilled the eligibility criteria and were included in this meta-analysis. The risk of a cardiac conduction defect was significantly higher among patients with NAFLD than in those without NAFLD, with a pooled odds ratio of 5.17 (95% confidence interval 1.34-20.01; I 2 96%). CONCLUSION: A significantly greater risk of cardiac conduction defects among patients with NAFLD was observed in this meta-analysis. How this risk should be managed in clinical practice requires further investigation.