Clinical factors associated with racial differences in the prevalence of occult hypoxemia: a retrospective case-control study.

Background: Recent studies showed that Black patients more often have falsely normal oxygen saturation on pulse oximetry compared to White patients. However, whether the racial differences in occult hypoxemia are mediated by other clinical differences is unknown. Methods: We conducted a retrospective case-control study utilizing two large ICU databases (eICU and MIMIC-IV). We defined occult hypoxemia as oxygen saturation on pulse oximetry within 92-98% despite oxygen saturation on arterial blood gas below 90%. We assessed associations of commonly measured clinical factors with occult hypoxemia using multivariable logistic regression and conducted mediation analysis of the racial effect. Results: Among 24,641 patients, there were 1,855 occult hypoxemia cases and 23,786 controls. In both datasets, Black patients were more likely to have occult hypoxemia (unadjusted odds ratio 1.66 [95%-CI: 1.41-1.95] in eICU and 2.00 [95%-CI: 1.22-3.14] in MIMIC-IV). In multivariable models, higher respiratory rate, PaCO2 and creatinine as well as lower hemoglobin were associated with increased odds of occult hypoxemia. Differences in the commonly measured clinical markers accounted for 9.2% and 44.4% of the racial effect on occult hypoxemia in eICU and MIMIC-IV, respectively. Conclusion: Clinical differences, in addition to skin tone, might mediate some of the racial differences in occult hypoxemia.

The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors: A Perspective From Global Burden of Disease Study 2019.

OBJECTIVES: Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking. MATERIALS AND METHODS: Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period. RESULTS: In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC -0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%). CONCLUSIONS: The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.

Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

PURPOSE: The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile. MATERIALS AND METHODS: This is a retrospective study of a prospectively collected registry of patients with MASLD and compensated advanced chronic liver disease (cACLD) who underwent EGR. Patients were categorized as (1) monotherapy: EGR alone and (2) combination therapy: GLP-1RA prescribed within 6 months prior to or after EGR. Outcomes included changes in noninvasive tests of hepatic fibrosis, weight profile, and insulin resistance status at 12 months. RESULTS: Thirty patients (body mass index 40.7 ± 9.3 kg/m2) were included. Of these, 12 patients (40%) underwent EGR monotherapy, and 18 patients (60%) underwent EGR + GLP-1RA combination therapy. Combination therapy group experienced greater improvements in fibrosis compared to monotherapy group (alanine aminotransferase: reduction by 55 ± 23% vs 29 ± 22% (p = 0.008), NAFLD fibrosis score: reduction by 181 ± 182% vs 30 ± 83% (p = 0.04), liver stiffness measurement on transient elastography: reduction by 54 ± 12% vs 14 ± 45% (p = 0.05)). There were greater reductions in hemoglobin A1c and homeostatic model assessment for insulin resistance in combination therapy compared to monotherapy (p < 0.05). At 12 months, the combination therapy group experienced 18.2 ± 6.6% TWL, while monotherapy group experienced 9.6 ± 3.3% TWL (p = 0.004). CONCLUSIONS: In patients with MASLD and cACLD, combination of EGR with GLP-1RA is associated with greater improvements in hepatic fibrosis, weight profile, and insulin resistance compared to EGR alone.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Changes in the Prevalence, Incidence, and Disability-Adjusted Life Years of Non-alcoholic Fatty Liver Disease in the United States Between 1990 and 2019.

INTRODUCTION: This study aimed to determine trends in the prevalence, incidence, and disability-adjusted life years (DALYs) of Non-alcoholic Fatty Liver Disease (NAFLD) in the US across different states and age groups between 1990 and 2019. METHODS: Using the Global Burden of Disease database, this study analyzed the prevalence, incidence, and DALYs of NAFLD in the US between 1990 and 2019. We computed relative percentage changes, performed Joinpoint regression analyses of trends, and compared these between states and age groups (5-19, 20-55, and more than 55 years old). RESULTS: In the United States, the prevalence of NAFLD increased more than the global average over the study period (+ 30.7% vs. + 24.5%), especially in the 5-19-year-old age group. Among all states, Kansas, Washington, and California had the highest increase in prevalence and the District of Columbia followed by Massachusetts and North Carolina had the lowest increase in prevalence. The increase in incidence was greater in the US than the global average (+ 37.18% vs. + 7.28%). West Virginia, Ohio, and Kentucky had the highest increase in incidence. The increase in DALYs was greater in the US compared to the global average (+ 57.15% vs. + 12.65%). Alaska, West Virginia, and Kentucky had the highest increase in DALYs. The increased incidence and DALYs were found in all states except in the District of Columbia. CONCLUSION: The prevalence of NAFLD in the US has increased more rapidly than the global average, especially in the pediatric population. South and Midwest states have the highest increase in prevalence, incidence, and DALYs of NAFLD. The District of Columbia was the only state that has decreased incidence and DALYs.

Endometriosis and Risk of Cardiovascular Disease: Systematic Review and Meta-Analysis.

Background: Endometriosis is a common disease affecting 10% of reproductive-age women globally and is associated with chronic systemic inflammation. Some studies suggest that women with endometriosis have a higher risk of cardiovascular disease, whereas others have conflicting findings. This study aims to further investigate the association between endometriosis and cardiovascular disease. Methods: A systematic review was conducted using the EMBASE and MEDLINE databases from inception to October 2022. The search strategy comprised terms for "endometriosis" and "cardiovascular disease." Eligible studies had to include one group of patients with endometriosis and another group of individuals without endometriosis. The study must then compare the incidence or prevalence of cardiovascular disease (major adverse cardiovascular events [MACE], ischemic heart disease [IHD], cerebrovascular accident [CVA], or peripheral artery disease [PAD]). Results: A total of 5,401 articles were identified, and 9 studies were eligible for meta-analysis. Pooled analysis showed an increased prevalence of IHD (pooled odds ratio [OR]: 1.22; 95% confidence interval [95% CI]: 0.74-2.02), CVA (pooled OR: 1.28; 95% CI: 1.07-1.53), and PAD (pooled OR: 1.55; 95% CI: 1.35-1.78). Pooled analysis showed an increased incidence of MACE (pooled hazard ratio [HR]: 1.23; 95% CI: 1.14-1.33), IHD (pooled HR: 1.43; 95% CI: 1.28-1.59), and CVA (pooled HR: 1.20; 95% CI: 1.11-1.30). Conclusions: This systematic review and meta-analysis found a statistically significant association between endometriosis and increased risk of cardiovascular disease (MACE, IHD, CVA, PAD).

The Efficacy of Cationic Amphiphilic Antihistamines on Outcomes of Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Cationic amphiphilic H1-antihistamines have demonstrated antitumor effects in preclinical studies. We conducted a retrospective cohort study to investigate their impact on patients with pancreatic adenocarcinoma (PDAC). METHODS: We performed a matched cohort study involving PDAC patients from two tertiary centers in Taiwan using criteria including age, sex, and cancer stage. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and objective response rates (ORR). RESULTS: We matched 28 cationic amphiphilic antihistamine users with 56 non-cationic amphiphilic antihistamine users. Cationic amphiphilic antihistamine users showed significantly longer OS (median 16.4 [IQR, 2.8 - 89.0] vs.5.8 [IQR, 2.0 - 9.8] months; p<0.001) and PFS (median 12.2 [IQR, 2.2 - 83.3] vs. 5.2 [IQR, 1.7 - 8.4] months; p=0.002) compared to non-users. In the Cox proportional hazard models, the use of cationic amphiphilic antihistamines was associated with approximately 60% lower risk of all-cause mortality and disease progression. Additionally, cationic amphiphilic antihistamine users exhibited a significantly greater ORR than non-users (39% vs. 7%, p=0.004). CONCLUSION: Our study suggests that cationic amphiphilic antihistamines are associated with improved survival outcomes in PDAC patients.

Increased Risk of Systemic Lupus Erythematosus in Patients with Chronic Urticaria: A Systematic Review and Meta-analysis.

Introduction: The association between systemic lupus erythematosus (SLE) and chronic urticaria (CU) has been suggested in the literature although the amount of evidence is still relatively limited. We aimed to combine all available studies on this association using systematic review and meta-analysis technique. Methods: Potentially eligible studies were identified from Medline and EMBASE from inception to February 2023 using search strategy that comprised of terms for "chronic urticaria" and "systemic lupus erythematosus". The eligible study must consist of one group of patients with CU and another group of comparators without CU and must compare the prevalence of SLE in each group and report effect size with 95% confidence intervals (95% CIs). We extracted such data from each study to calculate a pooled odds ratio using the generic inverse variance method with random-effect model. Funnel plot was used to evaluate publication bias. Newcastle-Ottawa Scale was used to appraise the methodological quality of the included studies. Results: A total of 5,155 articles were identified. After two rounds of independent review by four investigators, five studies met the eligibility criteria and were included in the meta-analysis. The meta-analysis found an increased prevalence of SLE among patients with CU compared with individuals without CU with the pooled odds ratio of 5.03 (95% CI, 2.57-9.85, I2 of 93%). Conclusion: This systematic review and meta-analysis found that patients with CU had a significantly increased risk of SLE compared to individuals without CU.

Rising incidence and impact of early-onset colorectal cancer in the Asia-Pacific with higher mortality in females from Southeast Asia: a global burden analysis from 2010 to 2019.

BACKGROUND AND AIM: Early-onset colorectal cancer (CRC) is a growing global health concern, especially in the Asia-Pacific region. However, comprehensive research on this topic from the region is lacking. Our study aims to investigate trends in early-onset CRC in Asia over 10 years, filling this research gap. METHODS: This study utilized data from the Global Burden of Disease Study 2019 to assess temporal trends in early-onset CRC in the Asia-Pacific. The analysis included estimating annual frequencies and age-standardized rates (ASRs) of early-onset CRC incidence, death, and disability-adjusted life-years (DALYs) by gender. RESULTS: The incidence of early-onset CRC significantly increased in both regions with higher increase and in the Western Pacific region. Notable increases were observed among males in the Western Pacific and females in Southeast Asia (SEA). Mortality rates remained stable in the Western Pacific but increased by 10.6% in SEA, especially among females. DALYs due to CRC also increased significantly in SEA, with a greater rise among females. The Western Pacific had the highest CRC incidence, and in SEA, the mortality rate was higher in females than males. CONCLUSIONS: Our study reveals a substantial increase in early-onset CRC in the Asia-Pacific underscoring the urgency for effective interventions. Thus, a comprehensive approach comprising controlled risk reduction, health promotion to heightened disease awareness, and implementation of effective screening strategies should be executed timely to mitigate the burden of early-onset CRC.

Global Epidemiology and Burden of Elderly-Onset Inflammatory Bowel Disease: A Decade in Review.

Inflammatory bowel disease (IBD), once thought to impact younger individuals, now manifests in approximately 10% of patients over 65, characterized by a heightened vulnerability to complications and greater diagnostic intricacies than conventional cases. However, comprehensive global epidemiological data regarding elderly-onset IBD are currently insufficient. Our study addresses this critical gap by analyzing trends in elderly-onset IBD over a decade, encompassing the estimation of annual frequencies and age-standardized rates of elderly-onset IBD burden for both genders, stratifying the data by geographical and sociodemographic factors. Our research highlights a notable increase in the proportion of elderly-onset IBD, constituting around 13% of all IBD cases. We observed a rising incidence in males, contrasted by a decreasing trend in females. The highest surge in incidence rates was seen in the Western Pacific region in both genders, but the highest burden was observed in America. Countries with high sociodemographic index (SDI) carried the greatest burden of elderly-onset IBD, while countries with low SDI had the least. The mortality and disability-adjusted life years (DALYs) rates trend downward in most regions. This study underscores an increasing incidence and proportion of IBD, particularly in elderly-onset IBD, particularly in males. While mortality and DALYs are decreasing in most regions, the overall burden remains highest in America and high-SDI countries. Effective public health interventions and comprehensive studies are required to tackle this mounting burden.

Gender, Age, and Regional Disparities in the Incidence and Mortality Trends of Infective Endocarditis in the United States Between 1990 and 2019.

The incidence of infective endocarditis (IE) has increased globally in the past decades, including in the United States. However, little is known about the differences in trends across states, gender, and age groups within the United States. Using the Global Burden of Disease database, we analyzed the incidence and mortality trends of IE in the United States between 1990 and 2019 using Joinpoint regression analyses, and compared between states, gender, and age groups. The age-standardized incidence rate (ASIR) of IE in the United States increased from 10.2/100,000 population in 1990 to 14.4 in 2019. The increase in ASIR was greater among men than women (45.8% vs 34.1%). The incidence increase was driven by 55+ year-olds (112.7% increase), with rapid increases in the 1990s and early 2000s, followed by a plateau around the mid-2000s. In contrast, the incidence among 5-to-19-year-olds decreased by -36.6% over the 30-year period. The incidence increased among all age groups in the last 5 years of observation (2015 to 2019), with the largest increase in 5-to-19-year-olds (3.3% yearly). The 30-year increase in ASIR was greatest in Utah (66.2%) and smallest in California (30.2%). The overall age-standardized mortality attributable to IE increased in the United States by 126% between 1990 and 2019 versus 19.6% globally. In conclusion, although the overall incidence and mortality of IE increased over the past 30 years in the United States, there are significant differences between regions, gender, and age groups. These findings indicate unevenly distributed disease burden of IE across the nation.

High parathyroid hormone level as a marker of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies have suggested that high parathyroid hormone (PTH) was associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), although the results from existing studies are inconsistent. Using systematic review and meta-analysis, we aimed to determine the association of PTH with NAFLD and NASH. METHODS: Potentially eligible studies were identified from Embase and Medline databases from using search strategy consisting of terms for "NAFLD/NASH", and "PTH". Eligible study must consist of one group of patients with NAFLD/NASH and another group without NAFLD/NASH. The study must provide mean ± SD PTH in both groups. We extracted such data to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using random-effects model. Funnel plot was used to assess for the presence of publication bias. RESULTS: A total of 388 articles were identified. After systematic review, 12 studies fulfilled the eligibility criteria and were included into the meta-analysis. The meta-analysis of 10 studies revealed the significant association between high PTH and NAFLD, with the pooled MD of 5.479 (95%CI 0.947-10.011, I2 82.4%). The funnel plot was symmetric and did not suggest publication bias. The meta-analysis of 4 studies revealed the non-significant association between high PTH and NASH, with the pooled MD of 11.955 (95%CI -4.703 - 28.614, I2 81.0%). CONCLUSIONS: High PTH level is significantly associated with NAFLD and can be used as a marker of NAFLD. However, high PTH level is non-significantly associated with NASH. Further studies are needed to increase the sample size and eliminate the confounding factors.

The prevalence and treatment outcomes of Helicobacter pylori infection in a tertiary hospital in Thailand, 2018-2021.

Background and Aim: Helicobacter pylori (HP) infection remains a significant global public health problem. This study aimed to study the prevalence of HP infection and treatment outcomes in Thailand. Methods: We retrospectively reviewed the results of the urea breath test (UBT) performed at the King Chulalongkorn Memorial Hospital between 2018 and 2021. The prevalence of HP infection was evaluated in dyspeptic patients undergoing UBT screening. In patients with known HP infection, the treatment regimen and the success rate in each patient were recorded. Results: One-thousand nine-hundred and two patients were included in this study. The prevalence of HP infection in dyspeptic patients was 20.77% (UBT was positive in 65 out of 313 patients). Of the 1589 patients who received the first treatment regimen, 1352 (85.08%) had a negative UBT result. Patients who failed in each treatment regimen were treated with subsequent regimens. The overall success rates for the second, third, and fourth regimens were 69.87% (109 of 156 patients), 53.85% (14 of 26 patients), and 50% (3 of 6 patients), respectively. Univariate logistic regression analysis found that using lansoprazole was associated with failure of treatment with OR = 2.11 (95% CI: 1.14-3.92, P = 0.018). Conclusion: Current primary HP treatment regimens have an eradication rate of >80%. Even though the previous regimens failed, without available antibiotic sensitivity results, the subsequent regimens were successful by at least 50%. In cases of multiple-treatment failure and where antibiotic sensitivity tests were unavailable, continuing to change regimens could provide satisfactory results.

Effect of Transoral Outlet Reduction on Hepatic Fibrosis in Roux-en-Y Gastric Bypass Patients with Weight Regain and Non-alcoholic Fatty Liver Disease.

PURPOSE: Weight regain after Roux-en-Y gastric bypass (RYGB) is associated with worsening of liver outcomes. However, the effect of transoral outlet reduction (TORe) on liver fibrosis in RYGB patients with weight regain and possible advanced fibrosis remains unknown. MATERIALS AND METHODS: This was a retrospective analysis of prospectively collected data of RYGB patients who underwent TORe for weight regain. Only patients with possible advanced fibrosis were included. TORe was performed using either an endoscopic suturing device (S-TORe) or plication device (P-TORe) to reduce the gastrojejunal anastomosis (GJA) and pouch sizes. Primary outcomes included changes in non-invasive tests (NITs) for fibrosis at 6-12 months. Secondary outcomes included weight loss and changes in insulin resistance and lipid profile at 6-12 months. RESULTS: Fifty RYGB patients were included. Baseline age and BMI were 55 ± 11 years and 40.1 ± 7.3 kg/m2. Baseline GJA and pouch sizes were 20 ± 7 mm and 5 ± 2 cm, respectively. Thirty patients (60%) underwent S-TORe and 20 patients (40%) underwent P-TORe. At 12 months following TORe, there were statistically significant improvements in NITs for fibrosis, including ALT, AST and FIB-4. There was a trend towards significant improvement in liver stiffness measurement on transient elastography. Patients experienced 8.8 ± 11.2% total weight loss (TWL) (p < 0.0001), with 60% experiencing at least 10% TWL. Additionally, there was a significant improvement in HbA1c and a trend toward significant improvement in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), suggestive of improved insulin sensitivity. CONCLUSION: TORe is associated with an improvement in hepatic fibrosis in patients with NAFLD and possible advanced fibrosis.

A Case of Bouveret's Syndrome Treated With Holmium:Yttrium-Aluminum-Garnet Laser.

Bouveret's syndrome is a rare form of gallstone ileus described as a gastric outlet obstruction from a gallstone that travels from the gallbladder to the bowel through a bilioenteric fistula. Despite its rarity, the mortality rate of this condition is high. Endoscopic treatment is preferred over surgery due to the association with lower mortality rate. To date, there are limited data about the application of holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy for fragmentation of gallstones in Bouveret's syndrome. We present the case of a 74-year-old man with multiple cardiac comorbidities who presented with periumbilical pain, decreased appetite, and vomiting. The patient had previously been admitted three months prior with acute cholecystitis, and a cholecystostomy tube was placed. He had leukocytosis and purulent discharge in his cholecystostomy bag. Computed tomography (CT) scan of the abdomen and pelvis showed a change in the position of a previously seen large gallstone from the neck of the gallbladder on the last admission, to the lumen of the duodenal bulb on this admission. This indicated the development of a cholecystoduodenal fistula, with the stone passing through this fistula into the duodenal bulb, causing the complete obstruction. Endoscopic treatment was recommended by the surgery team due to cardiac comorbidities and the significant friability of the tissue requiring laparotomy. Initial endoscopic evaluation showed complete obstruction of the duodenal bulb by a large smooth stone, not allowing passage of a guidewire beyond the stone. Therefore, holmium:YAG laser lithotripsy was used. After two sessions of laser therapy, four days apart, each breaking a pigmented and calcified stone, it eventually passed through the small bowel into the colon, relieving the obstruction. The patient had a favorable outcome and did not require surgery. This case report shows that holmium:YAG laser lithotripsy is capable of delivering favorable outcomes, as seen in a patient with a heavily calcified and pigmented stone, older age, and multiple comorbidities. Holmium:YAG laser could be considered for use with endoscopic equipment for future management of this condition, especially in patients who have medical comorbidities and heavily calcified gallstones.

Bone Mineral Density in Neurofibromatosis Type 1: A Systematic Review and Meta-Analysis.

To assess BMD in patients with neurofibromatosis type 1 (NF1) using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to February 2023 using search strategy that comprised terms for "Bone mineral density" and Neurofibromatosis type 1″. Eligible study must include adult or pediatric patients with NF1. The study must report mean Z-score with variance of total body, lumbar spine, femoral neck or total hip BMD of the studied patients. Point estimates with standard errors were retrieved from each study and were combined using the generic inverse variance method. A total of 1,165 articles were identified. After systematic review, 19 studies were included. The meta-analysis revealed that patients with NF1 had negative mean Z-scores for total body BMD (pooled mean Z-score -0.808; 95%CI, -1.025 to -0.591) and BMD at lumbar spine (pooled mean Z-score -1.104; 95%CI, -1.376 to -0.833), femoral neck (pooled mean Z-score -0.726; 95%CI, -0.893 to -0.560) and total hip (pooled mean Z-score -1.126; 95%CI, -2.078 to -0.173). The subgroup meta-analysis in pediatric patients aged < 18 years revealed that patients with NF1 had negative mean Z-scores for lumbar spine BMD (pooled mean Z-score -0.938; 95%CI, -1.299 to -0.577) and femoral neck BMD (pooled mean Z-score -0.585; 95%CI, -0.872 to -0.298). The current meta-analysis found that patients with NF1 had low Z-scores although the degree of low BMD may not be of clinical significance. The results do not support the role of early BMD screening in children and young adults with NF1.

Increased Prevalence of Gastroesophageal Reflux Disease Among Patients With Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: This study was conducted to determine the association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) by pooling the evidence from all available studies. METHODS: Potentially eligible studies were identified from MEDLINE and EMBASE database from inception to April 2021 employing a search strategy that consisted of terms for "Rheumatoid Arthritis" and "Gastroesophageal Reflux Disease". Eligible studies for the meta-analysis were recruited with conditions of being cohort studies that included rheumatoid arthritis and without rheumatoid arthritis individuals. Together with this, prevalence of GERD in both groups and the odds ratio (OR) comparing the prevalence of GERD between the two cohorts have been reported. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model and generic inverse variance method as described by DerSimonian and Laird. RESULTS: A total of 3,646 articles were identified. After two rounds of independent review by two investigators, five cohort studies were included in the meta-analysis as they met the eligibility criteria. The pooled analysis demonstrated a significant association between RA and GERD with the pooled odds ratio of 1.98 (95% CI, 1.49 - 2.65). High statistical heterogeneity with I2 of 83% was observed. The funnel plot was symmetric and publication bias was not observed. CONCLUSION: This systematic review and meta-analysis found a significant association between GERD and RA.

A Diagnostic Dilemma of a Case of Granulomatosis With Polyangiitis (GPA) Presenting With Thrombotic Vasculopathy.

Granulomatosis with polyangiitis (GPA) is a rare disease with a prevalence of about three in 100,000 persons in the United States. GPA is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis affecting predominantly small-sized vessels. It can present with localized or systemic symptoms with multiple organ involvement, thus making diagnosis challenging. Common skin lesions in GPA are palpable purpura, petechiae, ulcers, and livedo reticularis. These lesions usually have underlying vasculitis with or without granuloma on histology findings. To date, there have been no previous reports about thrombotic vasculopathy in GPA before. We present a case of a 25-year-old female who presented with intermittent joint pain for weeks, purpuric rash, and mild hemoptysis for a few days. A review of systems was notable for a 15-pound weight loss in one year. Physical examination was significant for a purpuric rash on the left elbow and toe, and left knee swelling and erythema. Presenting laboratory results were notable for anemia, indirect hyperbilirubinemia, mildly elevated D-dimers, and microscopic hematuria. Chest radiograph revealed confluent airspace disease. Extensive infectious workup was negative. A skin biopsy of her left toe revealed dermal intravascular thrombi without evidence of vasculitis. The thrombotic vasculopathy did not favor vasculitis but raised concern for a hypercoagulable state. However, extensive hematologic workup was negative. Bronchoscopy findings were consistent with diffuse alveolar hemorrhage. Later, cytoplasmic ANCA (c-ANCA) and anti-proteinase 3 (PR3) antibody titers were positive. Her diagnosis was unclear since both skin biopsy and bronchoscopy were nonspecific and inconsistent with her positive antibody results. The patient eventually underwent a kidney biopsy, which showed pauci-immune necrotizing and crescentic glomerulonephritis. Finally, a diagnosis of granulomatosis with polyangiitis was made based on the kidney biopsy and positive c-ANCA. The patient was treated with steroids and IV rituximab and discharged home with outpatient rheumatology follow-up. Due to multiple signs and symptoms including thrombotic vasculopathy, there was a diagnostic dilemma requiring a multidisciplinary approach. This case highlights the importance of pattern recognition for the diagnostic framework of rare disease entities and the multidisciplinary collaborative efforts required to reach the final diagnosis.

Genetic Variations of the Vitamin D Metabolic Pathway and COVID-19 Susceptibility and Severity: Current Understanding and Existing Evidence.

The immunomodulatory and metabolic effects of vitamin D receptor (VDR) activation have been considered beneficial in mitigating the susceptibility and severity of COVID-19 infection. Furthermore, vitamin D-binding protein (DBP) has pleiotropic effects on the immune system that may influence inflammation associated with COVID-19. Multiple observational studies have demonstrated an association between low levels of serum 25-hydroxyvitamin D and risk and the severity of COVID-19 infection. However, the impact of vitamin D supplementation as an adjunctive treatment for COVID-19 based on evidence from randomized clinical trials is unclear. Equally important is that certain variations of the genes involved in the vitamin D metabolic pathway have been shown to affect immune function and linked with various clinical outcomes, including cardio-metabolic disorders, autoimmune diseases, infections, and cancers. This indicates inter-individual difference in body response to vitamin D. There is also emerging evidence that common polymorphisms of these genes may influence the susceptibility and severity of COVID-19, although the confidence of these findings is limited by a small number of studies and participants. Further studies are needed to address the potential role of VDR activation and DBP in the pathophysiology of COVID-19 which take into account the genetic variations of vitamin D metabolic pathway.