Outcomes of endoscopic retrograde cholangiopancreatography in patients with inflammatory bowel disease: a nationwide study.

PURPOSE: Endoscopic retrograde cholangiopancreatography (ERCP) has become a commonly utilized procedure for both diagnostic and therapeutic purposes. There is a paucity of data for patients with inflammatory bowel disease (IBD) who undergo ERCP. The aim of this study is to examine the indications, complications, and inpatient outcomes of patients with IBD undergoing ERCP. METHODS: For this retrospective cohort study, we utilized the National Inpatient Sample database for the years 2018-2019. We compared potential indications, outcomes, ERCP-related procedures, and resource utilization in patients who underwent ERCP and had a diagnosis of IBD to that of patients who underwent ERCP without a diagnosis of IBD. We utilized a multivariate regression model that accounted for several potential confounders. RESULTS: We identified 318,590 ERCP procedures. Among them, 3625 ERCP procedures were performed in patients with an associated diagnosis of IBD. Patients with IBD who underwent ERCP had higher odds of acute kidney injury (aOR 1.27; 95% CI: 1.01-1.60) and sepsis (aOR 1.33; 95% CI: 1.07-1.67) compared to patients without IBD. However, inpatient mortality and other complications were not statistically different between the two groups. Patients with IBD were also less likely to undergo biliary sphincterotomy (aOR 0.75; 95% CI: 0.62-0.88) but there were no other differences in performance of ERCP-related therapeutic interventions between the two groups. Adjusted costs and charges were not statistically different between the two groups. CONCLUSION: Our study shows that ERCP is, overall, a safe procedure in patients with IBD, as inpatient morbidity and mortality are similar to patients without IBD.

The effects of provider-prescribed obesogenic drugs on post-laparoscopic sleeve gastrectomy outcomes: a retrospective cohort study.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is one of the most commonly performed bariatric procedures and has proven effective in providing weight loss. However, considerable variance has been noted in the degree of weight loss. Physician prescription practices may be negatively affecting weight loss post-LSG and, thus, contributing to the broad range of weight loss outcomes. The aim of our study was to determine whether commonly prescribed obesogenic medications negatively affect weight loss outcomes post-LSG. SUBJECTS/METHODS: This single center retrospective cohort study performed at a University hospital included 323 patients (≥18 years) within the University California, San Diego Healthcare System who underwent LSG between 2007 and 2016. We identified a list of 32 commonly prescribed medications that have weight gain as a side effect. We compared the percent excess weight loss (%EWL) of patients divided into two groups based on post-LSG exposure to obesogenic medications. A linear regression model was used to analyze %EWL at 12 months post-LSG while controlling for age, initial body mass index (BMI), and use of leptogenic medications. RESULTS: A total of 150 patients (Meds group) were prescribed obesogenic medications within the one-year post-LSG follow up period, whereas 173 patients (Control group) were not prescribed obesogenic medications. The Meds group lost significantly less weight compared to the Control group (%EWL ± SEM at 12 months 53.8 ± 2.4 n = 78, 65.0 ± 2.6, n = 84 respectively, P = 0.002). This difference could not be attributed to differences in age, gender, initial BMI, co-morbidities, or prescription of leptogenic medications between the two groups. CONCLUSIONS: The use of provider-prescribed obesogenic medications was associated with worse weight loss outcomes post-LSG. Closer scrutiny of patient medications may be necessary to help improve outcomes of weight loss treatments.

A multi-host approach for the systematic analysis of virulence factors in Cryptococcus neoformans.

A multi-host approach was followed to screen a library of 1201 signature-tagged deletion strains of Cryptococcus neoformans mutants to identify previously unknown virulence factors. The primary screen was performed using a Caenorhabditis elegans-C. neoformans infection assay. The hits among these strains were reconfirmed as less virulent than the wild type in the insect Galleria mellonella-C. neoformans infection assay. After this 2-stage screen, and to prioritize hits, we performed serial evaluations of the selected strains, using the C. elegans model. All hit strains identified through these studies were validated in a murine model of systemic cryptococcosis. Twelve strains were identified through a stepwise screening assay. Among them, 4 (CSN1201, SRE1, RDI1, and YLR243W) were previously discovered, providing proof of principle for this approach, while the role of the remaining 8 genes (CKS101, CNC5600, YOL003C, CND1850, MLH3, HAP502, MSL5, and CNA2580) were not previously described in cryptococcal virulence. The multi-host approach is an efficient method of studying the pathogenesis of C. neoformans. We used diverse model hosts, C. elegans, G. mellonella, and mice, with physiological differences and identified 12 genes associated with mammalian infection. Our approach may be suitable for large pathogenesis screens.

Polymerase chain reaction-based assays for the diagnosis of invasive fungal infections.

Currently accepted fungal diagnostic techniques, such as culture, biopsy, and serology, lack rapidity and efficiency. Newer diagnostic methods, such as polymerase chain reaction (PCR)-based assays, have the potential to improve fungal diagnostics in a faster, more sensitive, and specific manner. Preliminary data indicate that, when PCR-based fungal diagnostic assays guide antifungal therapy, they may lower patient mortality and decrease unnecessary antifungal treatment, improving treatment-associated costs and avoiding toxicity. Moreover, newer PCR techniques can identify antifungal resistance DNA loci, but the clinical correlation between those loci and clinical failure has to be studied further. In addition, future studies need to focus on the implementation of PCR techniques in clinical decision making and on combining them with other diagnostic tests. A consensus on the standardization of PCR techniques, along with validation from large prospective studies, is necessary to allow widespread adoption of these assays.

Safety of Immunizations for the Adult Patient With Inflammatory Bowel Disease-A Systematic Review and Meta-analysis.

BACKGROUND: Patients with inflammatory bowel disease (IBD) have low vaccination rates for vaccine-preventable diseases. Fear of adverse reactions (AEs) appear to negatively affect vaccination efforts. We aimed to systemically review the risks for AEs following immunization for patients with IBD. METHODS: We searched PubMed and Embase until April 15, 2020, for studies evaluating the safety of vaccinations among patients with IBD. The primary outcome was the incidence of systemic and local AEs among vaccinated patients. Secondary outcome was the rate of IBD flare following immunization. We utilized a random effects meta-analysis of proportions using the DerSimonian-Laird approach to estimate the safety of immunizations. RESULTS: A total of 13 studies with 2116 patients was included in our analysis after fulfilling our inclusion criteria. Seven studies examined the influenza vaccine, 4 the pneumococcal vaccine, 1 the recombinant zoster vaccine, and 1 the hepatitis B vaccine. Follow-up of patients was up to 6 months. The majority of AEs were local, with a pooled incidence of 24% (95% CI, 9%-42%) for all vaccines. Systemic AEs were mostly mild, without resulting in hospitalizations or deaths, with a pooled incidence of 16% (95% CI, 6%-29%) for all vaccines. Flare of inflammatory bowel disease after vaccination found with a pooled incidence of 2% (95% CI, 1%-4%) and we include in the analysis data from all immunizations examined. DISCUSSION: Our study demonstrated that AEs after vaccination are mainly local or mildly systemic and do not differ significantly from the expected AE after recommended immunizations for the general population. Thus, gastroenterologists should reinforce that vaccines are safe in patients with IBD.

Effect of Obesogenic Medications on Weight-Loss Outcomes in a Behavioral Weight-Management Program.

OBJECTIVE: This study aimed to evaluate a possible association between the use of obesogenic medications and inadequate weight loss in a behavioral weight-management program. METHODS: This is a case-control, single-center study of 666 adult patients within a Veterans Health Administration health system who participated in the MOVE! behavioral weight-loss program. The cohort was divided into responders (n = 150), patients who achieved ≥ 5% total weight loss by the end of the MOVE! program, and nonresponders (n = 516), those who achieved < 5% total weight loss. We reviewed each patient's medical records for exposure to obesogenic medication during the time of treatment. RESULTS: Approximately 62% (n = 411) of patients entering MOVE! had a prescription for obesogenic medications. Obesogenic medication use was associated with worse weight-loss outcomes, and participants were 37% less likely to achieve a clinically meaningful (≥ 5% total weight loss) outcome at the end of the MOVE! program (odds ratio, 0.633; 95% CI: 0.427-0.937; adjusted P = 0.022). Patients who received three or more medications (n = 72) had the greatest difficulty achieving 5% weight loss compared with the control group (odds ratio, 0.265; 95% CI: 0.108-0.646; adjusted P = 0.003). CONCLUSIONS: The use of provider-prescribed obesogenic medications was associated with worse weight-loss outcomes in a behavioral weight-loss program. Closer scrutiny of patient medications is necessary to help improve outcomes of weight-loss treatments.

SDH2 is involved in proper hypha formation and virulence in Candida albicans.

AIM: To investigate the role of SDH2 in Candida albicans filamentation and virulence. MATERIALS & METHODS: Caenorhabditis elegans and mouse candidiasis models were used to assess the virulence of a sdh2Δ/Δ mutant. Various hypha-inducing media were used to evaluate the hyphal development of C. albicans. DCFH-DA was used to measure intracellular Reactive Oxygen Species (ROS) levels. RESULTS: The sdh2Δ/Δ mutant was avirulent in the C. elegans model, hypovirulent in a murine candidiasis model, and defective to form filaments both in vitro and in vivo. Intracellular ROS level increased in the sdh2Δ/Δ mutant, and the filamentation defects of sdh2Δ/Δ were rescued by decreasing intracellular ROS. CONCLUSION: SDH2 plays an important role in C. albicans filamentation and virulence probably through affecting intracellular ROS. [Formula: see text].

Vaccinating the inflammatory bowel disease patient.

Current therapeutic options for patients with inflammatory bowel disease (IBD) include several agents that can alter their immune response to infections. Effective vaccines exist and offer protection against a number of infectious diseases. However, recent data has shown that IBD patients are inadequately vaccinated and, as a result, at risk to develop certain preventable infections. Furthermore, gastroenterologists' knowledge regarding the appropriate immunizations to administer to their IBD patients is suboptimal. This review article focuses on the current immunization schedule for the IBD patient and stresses the important role of the gastroenterologist as an active participant in the management of vaccination in their IBD patients.

Nocardiosis of the central nervous system: experience from a general hospital and review of 84 cases from the literature.

Central nervous system (CNS) nocardiosis is a rare disease entity caused by the filamentous bacteria Nocardia species. We present a case series of 5 patients from our hospital and a review of the cases of CNS nocardiosis reported in the literature from January 2000 to December 2011. Our results indicate that CNS nocardiosis can occur in both immunocompromised and immunocompetent individuals and can be the result of prior pulmonary infection or can exist on its own. The most common predisposing factors are corticosteroid use (54% of patients) and organ transplantation (25%). Presentation of the disease is widely variable, and available diagnostic tests are far from perfect, often leading to delayed detection and initiation of treatment. The optimal therapeutic approach is still undetermined and depends on speciation, but lower mortality and relapse rates have been reported with a combination of targeted antimicrobial treatment including trimethoprim/sulfomethoxazole (TMP-SMX) for more than 6 months and neurosurgical intervention.

The impact of antimicrobial resistance and aging in VAP outcomes: experience from a large tertiary care center.

BACKGROUND: Ventilator associated pneumonia (VAP) is a serious infection among patients in the intensive care unit (ICU). METHODS: We reviewed the medical charts of all patients admitted to the adult intensive care units of the Massachusetts General Hospital that went on to develop VAP during a five year period. RESULTS: 200 patients were included in the study of which 50 (25%) were infected with a multidrug resistant pathogen. Increased age, dialysis and late onset (≥ 5 days from admission) VAP were associated with increased incidence of resistance. Multidrug resistant bacteria (MDRB) isolation was associated with a significant increase in median length of ICU stay (19 vs. 16 days, p=0.02) and prolonged duration of mechanical ventilation (18 vs. 14 days, p=0.03), but did not impact overall mortality (HR 1.12, 95% CI 0.51-2.46, p=0.77). However, age (HR 1.04 95% CI 1.01-1.07, p=0.003) was an independent risk factor for mortality and age ≥ 65 years was associated with increased incidence of methicillin-resistant Staphylococcus aureus (MRSA) infections (OR 2.83, 95% CI 1.27-6.32, p=0.01). CONCLUSIONS: MDRB-related VAP is associated with prolonged ICU stay and mechanical ventilation. Interestingly, age ≥ 65 years is associated with MRSA VAP.

Fusarium infection: report of 26 cases and review of 97 cases from the literature.

Fusarium species is a ubiquitous fungus that causes opportunistic infections. We present 26 cases of invasive fusariosis categorized according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria of fungal infections. All cases (20 proven and 6 probable) were treated from January 2000 until January 2010. We also review 97 cases reported since 2000. The most important risk factors for invasive fusariosis in our patients were compromised immune system, specifically lung transplantation (n = 6) and hematologic malignancies (n = 5), and burns (n = 7 patients with skin fusariosis), while the most commonly infected site was the skin in 11 of 26 patients. The mortality rates among our patients with disseminated, skin, and pulmonary fusariosis were 50%, 40%, and 37.5%, respectively. Fusarium solani was the most frequent species, isolated from 49% of literature cases. Blood cultures were positive in 82% of both current study and literature patients with disseminated fusariosis, while the remaining 16% had 2 noncontiguous sites of infection but negative blood cultures. Surgical removal of focal lesions was effective in both current study and literature cases. Skin lesions in immunocompromised patients should raise the suspicion for skin or disseminated fusariosis. The combination of medical monotherapy with voriconazole or amphotericin B and surgery in such cases is highly suggested.

Update on the epidemiology and management of cryptococcal meningitis.

Despite recent improvements in the diagnosis and treatment of cryptococcosis, cryptococcal meningitis is responsible for > 600,000 deaths/year worldwide. The aim of this work is to provide an update on the developments in its epidemiology and management. Understanding the pathogenesis of Cryptococcus has improved, and new insights for the virulence of the fungus and the host response have enabled scientists to design new ways to confront this infection. Additionally, invertebrate model hosts have greatly facilitated the research in this field. Importantly, the epidemiology of Cryptococcus gattii has continued to evolve, and the emergence of this highly virulent species in immunocompetent populations, especially in Northwestern America and British Columbia, warrants increased awareness because delayed diagnosis and inappropriate antifungal therapy is associated with high mortality. Diagnosis remains a challenge, but new techniques for early and inexpensive identification of the pathogen are under development. Management can vary, based on the patient population (HIV-seropositive, organ transplant recipients or non-transplant/non-HIV). In most patients, amphotericin B with flucytosine continues to be the most appropriate induction therapy. However, in organ transplant recipients the use of liposomal amphotericin B improves mortality compared with deoxycholate amphotericin B. Also, the combination of amphotericin B with fluconazole seems to be a reasonable alternative, while fluconazole with flucytosine is superior to fluconazole monotherapy.

Central nervous system aspergillosis: a series of 14 cases from a general hospital and review of 123 cases from the literature.

Central nervous system (CNS) aspergillosis is a highly fatal infection. We review the clinical presentation, diagnosis, and outcome of this infection and present a case series of 14 consecutive patients with CNS aspergillosis admitted to Massachusetts General Hospital (MGH) from 2000 to 2011. We also review 123 cases reported in the literature during that time. We included only proven CNS aspergillosis cases conforming to the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) definitions of invasive fungal infections. In the MGH case series, neutropenia, hematologic malignancies, autoimmune diseases requiring steroid treatment, and solid organ transplantation were the predominant comorbid conditions. Notably, all MGH patients were immunosuppressed, and more than half (n = 8) had a history of previous brain injury, unrelated to their index hospitalization. For most MGH patients (11 of 14), the lung was the primary focus of aspergillosis, while 2 had paranasal sinus involvement, and 1 had primary Aspergillus discitis. Among reported cases, paranasal sinuses (27.6%) and the lung (26.8%) were the primary foci of infection, whereas 22% of those cases had no obvious primary organ involvement. Although a selection bias should be considered, especially among published cases, our findings suggest that patients who underwent neurosurgery had improved survival, with MGH and literature patients having 25% and 28.6% mortality, respectively, compared to 100% and 60.4%, respectively, among patients who received only medical treatment. Although this was not the case among MGH patients, CNS aspergillosis can affect patients without significant immune suppression, as indicated by the high number of reported immunocompetent cases. In conclusion, mortality among CNS aspergillosis patients remains high, and the infection may be more common among patients with previous brain pathology. When indicated, neurosurgical procedures may improve prognosis.

Using C. elegans for antimicrobial drug discovery.

INTRODUCTION: The number of microorganism strains with resistance to known antimicrobials is increasing. Therefore, there is a high demand for new, non-toxic and efficient antimicrobial agents. Research with the microscopic nematode Caenorhabditis elegans can address this high demand for the discovery of new antimicrobial compounds. In particular, C. elegans can be used as a model host for in vivo drug discovery through high-throughput screens of chemical libraries. AREAS COVERED: This review introduces the use of substitute model hosts and especially C. elegans in the study of microbial pathogenesis. The authors also highlight recently published literature on the role of C. elegans in drug discovery and outline its use as a promising host with unique advantages in the discovery of new antimicrobial drugs. EXPERT OPINION: C. elegans can be used, as a model host, to research many diseases, including fungal infections and Alzheimer's disease. In addition, high-throughput techniques, for screening chemical libraries, can also be facilitated. Nevertheless, C. elegans and mammals have significant differences that both limit the use of the nematode in research and the degree by which results can be interpreted. That being said, the use of C. elegans in drug discovery still holds promise and the field continues to grow, with attempts to improve the methodology already underway.