Class-Specific Relationship Between Use of Immunosuppressants and Risk for Community-Acquired Clostridioides difficile Infection.

BACKGROUND: Immunosuppressant exposure is associated with risk for Clostridioides difficile infection (CDI). It is unknown whether this risk is shared equally across immunosuppressant classes. METHODS: This was a retrospective cohort study. Adults were included if they were tested for community-acquired CDI (CA-CDI) by stool polymerase chain reaction within 72 hours of hospitalization between 2010 and 2019. The primary outcome was CA-CDI requiring hospitalization, defined as a positive stool test. The primary exposure was use of a home immunosuppressant, at any dose or duration, defined based on the medication reconciliation, and categorized as systemic steroids, calcineurin inhibitors, antimetabolites, anti-tumor necrosis factor-alpha agents, anti-CD20 antibody, and all others. RESULTS: A total of 10 992 hospitalized patients met criteria for the study including 1793 (16%) with CA-CDI; 23% used 1 or more immunosuppressant class. Among those immunosuppressed, 27% tested positive for CA-CDI compared with 22% among those who were not immunosuppressed (P < .01). After adjustment, calcineurin inhibitors (adjusted odds ratio [aOR], 1.19; 95% confidence interval [CI], 1.01-1.44) were associated with increased risk for CA-CDI. Risk for CA-CDI rose with multiple immunosuppressant classes: aOR, 1.22; aOR, 1.53; and aOR, 2.40 for 2, 3, and 4 classes, respectively. After excluding those with solid organ transplant, the relationship between use of calcineurin inhibitors and CDI increased (aOR, 2.21; 95% CI, 1.40-3.49). CONCLUSIONS: The greatest risk for CA-CDI was observed among patients using multiple classes of immunosuppressants and those using calcineurin inhibitors. Future studies should recognize that CDI risk differs based on immunosuppressant class.

Clinical Factors Associated With Positive Stool PCR for Gastrointestinal Pathogens in Celiac and Inflammatory Bowel Disease.

GOALS: We aimed to identify the clinical factors of celiac disease (CeD) and inflammatory bowel disease (IBD) associated with positive stool gastrointestinal (GI) polymerase chain reaction (PCR) test. BACKGROUND: Understanding the pattern of enteric infections in CeD and IBD may allow further insight into microbiome-mediated pathogeneses. STUDY: This was a retrospective study of adult patients (age 18 y or above) with CeD and IBD at a large quaternary care institution. We identified patients with CeD or IBD who underwent stool GIPCR evaluation as outpatients (office visit or at endoscopy) between March 2015 and March 2019. Patients with a negative GIPCR test within the study time frame were randomly chosen as controls (1 : 1). The independent relationship between clinical characteristics and positive GIPCR was evaluated using multivariable logistic regression. RESULTS: A total of 266 patients met criteria for the study, including 92 (35%) with CeD and 174 (65%) with IBD. On multivariable analysis of factors associated with positive GIPCR test, CeD patients were more likely to have diarrheal presentation of illness [odds ratio (OR): 2.61, 95% confidence interval (CI) 1.05-6.72], experience extraintestinal manifestations (OR: 2.49, 95% CI: 1.01-6.31), and practice a gluten-free diet for at least 5 years (OR: 4.00, 95% CI: 1.36-11.67), relative to those with a negative GIPCR test. IBD patients with positive GIPCR were more likely to be on corticosteroids (OR: 2.23, 95% CI: 1.02-5.4.84), experience extraintestinal manifestations (OR: 2.60, 95% CI: 1.22-5.53), and use proton-pump inhibitors (OR: 4.07, 95% CI: 1.69-9.77). CONCLUSIONS: Intestinal infections in CeD and IBD are associated with important disease-specific characteristics.

The Distribution of Gastrointestinal Pathogens on Stool PCR Prior to the Development of IBD.

GOALS: We investigated the distribution of pathogens on stool gastrointestinal (GI) polymerase chain reaction (PCR) testing in those who subsequently developed inflammatory bowel disease (IBD). BACKGROUND: Infectious gastroenteritis has been associated with later development of IBD. STUDY: This retrospective study includes patients of all ages hospitalized for diarrhea with positive GIPCR panel and subsequently a new diagnosis of IBD [confirmed by chart review and International Classification of Disease, Clinical Modification code for Crohn's disease (CD) or ulcerative colitis (UC)], between March 2015 to September 2019 at our quaternary care institution. Patients with IBD diagnosis before GIPCR were excluded. Descriptive statistics characterized the distribution of microbial pathogens in relation to later IBD diagnosis. RESULTS: Fifty-four participants were eligible (UC 44%; CD 56%). Median age at time of IBD diagnosis was 35 years [interquartile range (IQR) 18 to 65]. Median time between GIPCR and IBD diagnosis was 3 months (IQR 2 to 9) for all patients. When stratified by organism class, median time to diagnosis was 6 months (IQR 2 to 10) for patients with bacteria, 3 months (IQR 1 to 8) for patients with viruses, and 1 month (IQR 0.75 to 1) for patients with parasites (log-rank P=0.001). Sixty-nine unique pathogens (83% bacteria) were identified on all tests. Escherichia coli was the most common species (71%), of which enteropathogenic E. coli was predominant (38%). CONCLUSIONS: The E. coli species, specifically enteropathogenic E. coli, may be implicated in the development of IBD. This is one of the first studies to evaluate the results of stool GIPCR in the link between the microbiome and IBD pathogenesis.

A Simple Emergency Department-Based Score Predicts Complex Hospitalization in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Thirty percent of inflammatory bowel disease (IBD) patients hospitalized with flare require salvage therapy or surgery. Additionally, 40% experience length of stay (LOS) > 7 days. No emergency department (ED)-based indices exist to predict these adverse outcomes at admission for IBD flare. We examined whether clinical, laboratory, and endoscopic markers at presentation predicted prolonged LOS, inpatient colectomy, or salvage therapy in IBD patients admitted with flare. METHODS: Patients with ulcerative colitis (UC) or colonic involvement of Crohn's disease (CD) hospitalized with flare and tested for Clostridioides difficile infection (CDI) between 2010 and 2020 at two urban academic centers were studied. The primary outcome was complex hospitalization, defined as: LOS > 7 days, inpatient colectomy, or inpatient infliximab or cyclosporine. A nested k-fold cross-validation identified predictive factors of complex hospitalization. RESULTS: Of 164 IBD admissions, 34% (56) were complex. Predictive factors included: tachycardia in ED triage (odds ratio [OR] 3.35; confidence interval [CI] 1.79-4.91), hypotension in ED triage (3.45; 1.79-5.11), hypoalbuminemia at presentation (2.54; 1.15-3.93), CDI (2.62; 1.02-4.22), and endoscopic colitis (4.75; 1.75-5.15). An ED presentation score utilizing tachycardia and hypoalbuminemia predicted complex hospitalization (area under curve 0.744; CI 0.671-0.816). Forty-four of 48 (91.7%) patients with a presentation score of 0 (heart rate < 99 and albumin ≥ 3.4 g/dL) had noncomplex hospitalization. CONCLUSIONS: Over 90% of IBD patients hospitalized with flare with an ED presentation score of 0 did not require salvage therapy, inpatient colectomy, or experience prolonged LOS. A simple ED-based score may provide prognosis at a juncture of uncertainty in patient care.

Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis.

BACKGROUND: Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. METHODS: Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. RESULTS: One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. CONCLUSIONS: HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.

Patients with More Severe IBD Get Clostridioides difficile Rather than Clostridioides difficile Increasing the Severity of IBD.

BACKGROUND: Inflammatory bowel disease (IBD) patients who have Clostridioides difficile infection (CDI) have worse outcomes. AIMS: We aimed to determine whether such outcomes are the result of CDI or whether CDI occurs in patients who have more severe IBD. METHODS: This was a retrospective study of patients hospitalized for ≥ 2 IBD flares from 2010 to 2019. The primary outcome was time to IBD flare between hospitalizations. First, time to flare was compared between patients who were hospitalized for a flare complicated by CDI and subsequently for a CDI-negative flare (cohort A, denoted +/-) versus patients who were hospitalized for two CDI-negative flares (cohort B, -/-). Second, time between flares was compared within the subset of cohort A patients who had three flares (cohort C, -/+/-) before and after CDI. RESULTS: Time between flares was a median of 4 months (IQR 1-9) among 51 cohort A patients versus 12 months (IQR 6-38) among 51 cohort B patients (log-rank P < 0.01). In contrast, the median time between flares was similar within cohort C before and after CDI (log-rank P = 0.54). At time of the second IBD flare, patients in cohort A (+/-) were more likely to have moderate or severe disease compared to patients in cohort B (-/-). CONCLUSIONS: Patients with prior CDI had shorter time to subsequent IBD flare relative to their CDI-negative counterparts. This is not likely due to CDI itself because there was no difference in time between flares before versus after acquiring CDI. Rather, patients who acquire CDI may have more severe IBD.

Gynecologic cancer in HIV-positive women: a systematic review and meta-analysis.

BACKGROUND: While there is a significant body of literature on cervical cancer in HIV-positive women, little is known about other gynecologic cancers in this population. OBJECTIVE: The objective of this systematic review and meta-analysis is to describe the incidence, presentation, treatment, and outcomes for HIV-positive women with non-acquired immunodeficiency syndrome-defining gynecologic cancers. STUDY DESIGN: We searched MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials for English-language studies published from 2000 to May 1, 2017. Studies containing 1 or more HIV-positive women with endometrial, ovarian, or vulvovaginal cancer and reporting incidence, treatment regimen, or survival were included. Two authors independently reviewed abstracts and full-text articles for inclusion and assessed study quality (details of the review protocol were registered as PROSPERO-CRD42017064525). Pooled estimates of incidence were calculated using random-effects models. Pooled estimates of cancer presentation and outcomes were averaged from case studies. RESULTS: Of 5744 abstracts screened, we identified 70 articles on 58 studies on 292,202 women with HIV and 528 women with HIV and gynecologic cancer for inclusion. Most articles (53%) focused on incidence, and only 3, 4, and 20 articles focused on treatment and outcomes of endometrial, ovarian, and vulvovaginal cancers, respectively. The standardized incidence ratios for endometrial, ovarian, and vulvovaginal cancers were 4.38 (95% confidence interval 0.26-8.49) for endometrial cancer, 3.21 (95% confidence interval 2.29-4.13) for ovarian cancer, and 21.93 (95% confidence interval 13.50-30.35) for vulvovaginal cancer. Fifty-seven percent of women were diagnosed at an early stage, and all received cancer treatment. CONCLUSION: In women with HIV, the incidence of ovarian and vulvovaginal cancer were higher than the general population, while incidence of endometrial cancer was similar. However, there was a paucity of data on treatment and outcomes for non-acquired immunodeficiency syndrome-defining gynecologic cancers. Given the increased incidence of gynecologic cancer, specific research on this population is essential to improve treatment and outcomes for HIV-positive women.

Surgery After an Initial Episode of Uncomplicated Diverticulitis: Does Time to Resection Matter?

BACKGROUND: The aim of this study was to determine whether time to surgery after an initial episode of uncomplicated diverticulitis is associated with undergoing an emergent versus an elective resection. METHODS: In this retrospective, administrative claims database study, we identified patients at least 18 y old in the 2005-2011 California State Inpatient Database who had an initial episode of uncomplicated diverticulitis and then underwent a bowel resection within 2 y. After characterizing the distribution in time to surgery among all patients, we used a multivariable logistic regression to determine whether time to surgery was associated with undergoing an emergent resection. Next, we assessed differences in three outcomes between elective and emergent resections: at least one of eight postoperative complications, extended length of stay (defined as the top decile of hospitalizations), and 30-d inpatient readmissions. Analyses adjusted for time between initial hospitalization and resection, number of inpatient hospitalizations for diverticulitis before the resection, clinical factors, and hospital clustering. RESULTS: We identified 4478 patients with an initial episode of uncomplicated diverticulitis followed by a bowel resection within the subsequent 2 y. One-fifth (21.1%) underwent an emergent resection. The median time from the initial episode to resection was 3.8 mo (IQR: 2.3-8.1 mo) for elective resections and 5.1 mo (IQR: 2.3-12.4 mo) for emergent resections. The adjusted odds of undergoing an emergent relative to an elective resection increased by 7% (aOR 1.07 [1.02-1.11]) for every 3 passing mo. Emergent resections were associated with greater adjusted odds of complications (adjusted odds ratio [aOR] 1.75 [95%-CI 1.43-2.15]), extended LOS (aOR 4.52 [3.31-6.17]), and 30-d readmissions (aOR 1.49 [1.09-2.04]). CONCLUSIONS: Among patients who experienced an initial episode of uncomplicated diverticulitis and eventually underwent a resection, the odds of having an emergent relative to elective surgery increased with every 3 passing mo. These findings may inform the management of uncomplicated diverticulitis for high-risk patients eventually needing surgery.

Use of Breast Milk and Other Feeding Practices Following Gastrointestinal Surgery in Infants.

OBJECTIVES: The aim of the study was to characterize the enteral feeding practices in infants after gastrointestinal surgery. METHODS: We performed a retrospective analysis of infants who underwent intestinal surgery at age <6 months who survived to be fed enterally between January 2012 and June 2017. Demographics, surgical characteristics, feeding practices, and growth-related outcomes during hospitalization, discharge, and follow-up (3, 6, and 12 months) were obtained from the electronic medical records. Descriptive statistics compared infants by their initial diagnosis. RESULTS: We reviewed 111 infants: necrotizing enterocolitis (NEC) = 21, gastroschisis = 28, atresia = 27, spontaneous intestinal perforation (SIP) = 18, and other diagnoses = 17. Most infants (77%) received mother's milk (MM) as the first postoperative feed, but this differed by diagnosis (P = 0.004). Donor milk was used in 11%, most commonly in infants with NEC and SIP. Infants with NEC were least likely to continue MM in the hospital (7%, P = 0.0014) and were more likely to receive elemental formula. Only 44% of infants received MM at discharge. After 1 year, 25% were fed MM. The majority of infants were discharged with feeding tubes (nasogastric: 35%, gastric: 23%). Although all groups had acceptable weights at discharge, infants with NEC (z score: -1.8) and SIP (z score: -1.1) showed growth failure at 3 months (z scores: -3.3, -3.2, respectively, P < 0.0001), but had appropriate gain by 1 year (z scores: -1.1, -1.7, respectively). CONCLUSIONS: Despite most infants receiving MM in the early postoperative period, <50% at discharge and only 33% at 1-year still received MM. Weight gain after discharge in infants with NEC and SIP warrants close monitoring.

Is there evidence of a July effect among patients undergoing hysterectomy surgery?

BACKGROUND: It is hypothesized that the quality of health care decreases during trainee turnovers at the beginning of the academic year. The influx of new gynecology and surgery residents into hospitals in this setting may be associated with poorer surgical outcomes, known as the July effect. OBJECTIVE: We sought to systematically study hysterectomy outcomes in the state of Maryland during the 3-month period July through September as compared to all other months of the academic year, in order to assess for the presence of a July effect in hysterectomy surgery. STUDY DESIGN: This is a retrospective study of the Maryland Health Services Cost Review Commission Database from July 2012 through September 2015 focused on women undergoing hysterectomies for benign or malignant disease, either by obstetricians and gynecologists or gynecologic oncologists, during July through September vs October through June. Multivariable logistic regressions accounted for clustering by hospitals and adjusted for several cofactors. The primary outcome includes at least 1 of 11 major perioperative in-hospital complications; the secondary outcomes were extended postoperative length of stay (defined as >2 days) and 30-day inpatient readmission rates. RESULTS: We identified 6311 hysterectomies (78.2% benign) performed by 424 surgeons at 20 academic hospitals. Patients were primarily white (42.8%), 45-64 years old (54.4%), and had private insurance (66.3%). The unadjusted rate of in-hospital complications was 16.8%, extended length of stay was 30.3%, and 30-day readmissions was 6.6%. After adjustment, patients undergoing hysterectomies during July through September did not have more adverse outcomes relative to those undergoing surgery at other times of the year: complications (adjusted odds ratio, 0.87; 95% confidence interval, 0.75-1.01), length of stay >2 days (adjusted odds ratio, 1.03; 95% confidence interval, 0.90-1.19), and 30-day readmissions (adjusted odds ratio, 0.99; 95% confidence interval, 0.80-1.23). Sensitivity analyses assessing individual complications, hysterectomy outcomes at nonacademic hospitals, and benign vs malignant indications for hysterectomies yielded similar findings. CONCLUSION: Women in Maryland undergoing hysterectomy surgery at academic hospitals during July through September of the academic year did not experience worse outcomes relative to women having surgery in other months. Additional studies are necessary to further assess the possibility of a July effect in hysterectomy on a national basis. Institutions should continue to provide effective surgical training environments for new interns and residents transitioning to more senior roles, while maintaining optimal patient safety.

Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series.

BACKGROUND: We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers. METHODS: This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors. RESULTS: Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn's disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years. CONCLUSIONS: Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.

We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD) by using a case-controlled series method, which allows for controlling of residual confounding. We studied ambulatory IBD patients who were tested for enteric infection from 2015 to 2019 and received PPIs for some of this period. Rates of enteric infections were compared between the PPI exposed period vs pre- and post-PPI periods identical in duration to the exposed period. We found that PPIs were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.

The Development of Persistent Gastrointestinal Symptoms in Patients With Melanoma Who Have Had an Immune Checkpoint Inhibitor-Related Gastrointestinal Toxicity.

INTRODUCTION: Immune-related adverse events (irAE) secondary to immune checkpoint inhibitors (ICI) have gastrointestinal (GI) manifestations, including gastritis, enteritis, and/or colitis. The long-term sequelae of ICI-associated GI toxicities (GI-irAE), particularly the development of disorders of gut-brain interaction, are not well known. We characterized the incidence of persistent GI symptoms after GI-irAE. METHODS: This is a retrospective study of adults with melanoma treated with ICI and diagnosed with GI-irAE at our institution from 2013 to 2021. All patients had endoscopic and histologic evidence of GI-irAE. The primary outcome was incidence of persistent GI symptoms (diarrhea, abdominal pain, bloating, constipation, fecal incontinence, nausea, vomiting) after resolution of GI-irAE. Hazard ratios evaluated the association between parameters and time to persistent GI symptoms. RESULTS: One hundred four patients with melanoma (90% stage IV disease) and GI-irAE met inclusion criteria. Thirty-four percent received anti-cytotoxic T lymphocyte-associated protein-4 therapy, 33% anti-programmed death-1, and 34% dual therapy. Patients were treated for GI-irAE for an average of 9 ± 6 weeks. Twenty-eight (27%) patients developed persistent GI symptoms 1.6 ± 0.8 years after GI-irAE. The most common symptom was constipation (17%), followed by bloating (8%) and diarrhea (5%). Over 453 person-years, the incident rate was 6.2% per 100 person-years. Use of cytotoxic T lymphocyte-associated protein-4 single or dual therapy was associated with a 3.51× risk of persistent GI symptoms (95% confidence interval 1.20-10.23). DISCUSSION: In this cohort of melanoma patients who experienced GI-irAE, 26% developed persistent GI symptoms, most frequently constipation. Future studies should characterize the GI sequelae after GI-irAE, which may shed light on disorders of gut-brain interaction pathogenesis and improve the lives of cancer survivors.

Novel Drug Therapeutics in Celiac Disease: A Pipeline Review.

Celiac disease (CeD) is a chronic, autoimmune systemic disorder triggered by the ingestion of gluten, a protein found in foods such as wheat, rye, and barley. The only effective treatment for CeD is complete removal of gluten from the diet. A strict gluten-free diet (GFD) results in symptomatic, serologic, and histologic remission in most patients. However, GFD may fail to induce clinical or histologic improvement and some patients may alternatively have difficulty strictly adhering to the GFD for other reasons. Despite this, there are currently no FDA-approved drugs for the treatment of CeD. The complex pathogenic process of CeD is becoming increasingly studied and better understood, enabling the identification of various targets for future therapies. Mechanisms under evaluation include probiotics, digestion of peptides, gluten sensitization, tight junction modulation, deamidation, and immune targets. Multiple investigational drugs are in the pipeline, and several drug candidates have entered late-phase clinical trials. Indeed, current and future studies are needed to target specific etiological mechanisms and provide an alternative to GFD alone. This review provides a broad overview of the various investigative treatment approaches for CeD, summarizing the latest progress in the pipeline.

Clinical characteristics associated with small airways disease in systemic sclerosis.

Objective: Pulmonary manifestations of systemic sclerosis are a major cause of morbidity and mortality. Small airways disease can cause dyspnea and pulmonary function test abnormalities. We aimed to determine the prevalence of small airways disease and describe the characteristics associated with small airways disease in a cohort of systemic sclerosis patients. Methods: We performed a retrospective cohort study of adults with systemic sclerosis who met American College of Rheumatology/European League Against Rheumatism 2013 classification criteria and were evaluated at our institution between November 2000 and November 2015. Patients with prior lung transplantation were excluded. Small airways disease was defined as the presence of one or more of the following: airway-centered fibrosis on surgical lung biopsy, forced expiratory volume at 25-75% ⩽ 50% on pulmonary function tests, and/or high-resolution computed tomography scan of the chest with bronchiolitis, mosaic attenuation, or air trapping on expiratory views. The primary outcome was small airways disease diagnosis. We performed multivariable logistic regression to determine the association of clinical variables with small airways disease. Results: One-hundred thirty-six systemic sclerosis patients were included; 55 (40%) had small airways disease. Compared to those without small airways disease, a significantly greater proportion of those with small airways disease had interstitial lung disease, chronic obstructive pulmonary disease, pulmonary hypertension, and gastroesophageal reflux disease. On multivariable analysis, pulmonary hypertension (odds ratio = 2.91, 95% confidence interval = 1.11-7.65, p-value = 0.03), gastroesophageal reflux disease (odds ratio = 2.70, 95% confidence interval = 1.08-6.79, p-value = 0.034), and anti-topoisomerase I (anti-Scl-70) antibody positivity (odds ratio = 0.42, 95% confidence interval = 0.19-0.93, p-value = 0.033) were associated with diagnosis of small airways disease. Conclusion: Small airways disease is prevalent among systemic sclerosis patients; those with pulmonary hypertension or gastroesophageal reflux disease may have a higher risk of small airways disease.

Doxycycline-induced cholestatic liver injury.

Doxycycline-induced liver injury is a rare phenomenon, with an unclear clinical course and etiopathogenesis. The onset of injury may be acute-to-subacute, with a pattern ranging from hepatocellular or cholestatic to mixed, and it often lasts up to several weeks. We present a case of cholestatic liver injury secondary to doxycycline use in a middle-aged woman. In patients with a history of doxycycline exposure and subsequent hepatic injury, an adverse drug reaction due to doxycycline should remain on the differential, and immediate removal of the offending agent with close monitoring of the clinical condition should be pursued.

Hodgkin lymphoma presenting as alcohol-induced back pain.

A 32-year-old Chinese man without significant medical history presented with a 2-month history of worsening lumbosacral back pain radiating to the groin and left lower extremity. He also described a shooting pain in the sciatic nerve distribution that began with and was exacerbated by alcohol consumption, a rare but known symptom of Hodgkin lymphoma (HL). On exam, an anterior chest wall mass was noted. Radiographic evaluation of an anterior mediastinal mass showed osseous erosion into the manubrium. MRI of the lumbar spine showed diffuse osseous disease of the lower thoracic and lumbar spine with extension into the right sacroiliac joint and S2 neural foramen without vertebral body collapse or stenosis. Tissue biopsy revealed nodular sclerosis HL, stage IVB IPS2. The patient was primary refractory to ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) therapy. Salvage ICE (ifosfamide, carboplatin, etoposide) chemotherapy was used and then followed by non-myeloablative haploidentical bone marrow transplant was performed on 5 March 2019.

Initial medical and surgical management of inflammatory bowel disease in the biologic era: A comparison between the United States and China.

BACKGROUND AND AIMS: We compared the initial medical and surgical management of Crohn's disease (CD) and ulcerative colitis (UC) between the United States and China, with aims to better characterize the global variation in the treatment patterns of inflammatory bowel disease (IBD). METHODS: Participants from the United States and China completed a questionnaire on demographic and clinical characteristics, medications (biologics, immunomodulators, aminosalicylates, steroids), and IBD-related surgical history. Patients diagnosed in 2006 and later were eligible. Analysis was restricted to treatment patterns within 1 year of diagnosis. Multivariable logistic regressions examined differences by country. RESULTS: We recruited 202 CD (US: 49%, China: 51%) and 133 UC (US: 63%, China: 37%) participants. Median age at survey was 31 years (range: 18-76) and at diagnosis was 28 years (range: 12-70). Biologics were commonly used in the United States for CD (66%) and UC (28%) and less commonly in China for CD (19%) and UC (0%). On regression, US CD participants were more likely to receive biologics (odds ratio [OR] 23.82 [95% confidence interval [CI] 8.98-63.14]), aminosalicylates (OR 4.93 [2.00-12.15]), and steroids (OR 4.36 [1.87-10.16]). US UC participants were more likely to receive immunomodulators (OR 3.45 [1.09-10.90]) and steroids (OR 3.31 [1.55-7.06]). There existed minimal differences regarding undergoing surgery for CD (US: 16%, China: 16%) and UC (US: 5%, China: 2%). A proportion (US: 12%, China: 19%) underwent IBD-related surgery prior to diagnosis (median: 5 years; range: 1-39). CONCLUSION: US, relative to Chinese, participants were more likely to report early biologic use. There were no differences between countries in undergoing early surgery. Evaluating global practice variation is integral to optimizing early pharmacological therapy and timing of surgery for patients with IBD.

Comparative Effects of Medical Versus Surgical Weight Loss on Body Composition: a Pilot Randomized Trial.

OBJECTIVE: Bariatric surgery leads to more rapid and greater weight loss (WL) compared to medical weight loss (MWL), but the differences in body composition (BC) changes for these modalities remain unclear. Due to the known health risks associated with central adiposity, we compared the changes in regional distribution of fat mass (FM) and lean mass (LM) after surgical versus MWL. METHODS: In this 1:1:1 randomized trial among 15 persons with type 2 diabetes and body mass index (BMI) 30-39.9 kg/m2, we compared changes in BC, by dual-energy X-ray absorptiometry and abdominal computerized tomography, at time of 10%WL or 9 months after intervention (whichever came first). Participants underwent MWL, adjustable gastric banding (AGB), or Roux-en-Y gastric bypass (RYGB). Non-parametric tests evaluated BC differences (FM, LM, and visceral adipose tissue [VAT]) within and across all three arms and between pair-wise comparisons. RESULTS: Twelve female participants (75% African American) completed the study. Patient age, BMI, and baseline anthropometric characteristics were similar across study arms. AGB lost more LM (MWL - 5.2%, AGB - 10.3%, p = 0.021) and VAT (MWL + 10.9%, AGB - 28.0%, p = 0.049) than MWL. RYGB tended to lose more VAT (MWL +10.9%, RYGB - 20.2%, p = 0.077) than MWL. AGB tended to lose more LM than RYGB (AGB - 12.38%, RYGB - 7.29%, p = 0.15). CONCLUSIONS: At similar WL, AGB lost more LM and VAT than MWL; RYGB similarly lost more VAT. Given the metabolic benefits of reducing VAT and retaining LM, larger studies should confirm the changes in BC after surgical versus medical WL. CLINICAL TRIAL REGISTRATION: NCTDK089557 - ClinicalTrials.gov.