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Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Background Anxiety and depression are comorbid disorders with IBD and are associated with poor outcomes. Resilience is an innate but modifiable trait that may improve the symptoms of psychological disorders. Increasing resilience may decrease the severity of these comorbid disorders, which may improve IBD outcomes. The aim of this study was to describe the association between resilience, anxiety, and depression in IBD patients. Methods We performed a cross-sectional study of IBD patients. Patients completed a questionnaire consisting of the Connor-Davidson Resilience Scale (CD-RISC), a measure of resilience, the Generalized Anxiety Disorder 7 (GAD-7), and the Patient Health Questionnaire-9. Primary outcome was severity of anxiety and depression in patients with high resilience. Multivariable linear regression analysis evaluated the association between severity of anxiety and depression and level of resilience. Results A sample of 288 patients was analyzed. Bivariable linear regression analysis showed a negative association between resilience and anxiety (Pearson rho = −0.47; P < .0001) and between resilience and depression (Pearson rho = −0.53; P < .0001). Multivariable linear regression indicated that high resilience is independently associated with lower anxiety and that for every 1-unit increase in CD-RISC, the GAD-7 score decreased by 0.04 units (P = .0003). Unlike anxiety, the association between resilience and depression did not remain statistically significant on multivariable analysis. Conclusions High resilience is independently associated with lower anxiety in IBD patients, and we report a quantifiable decrease in anxiety score severity for every point of increase in resilience score. These findings suggest that IBD patients with higher resilience may have better coping mechanisms that buffer against the development of anxiety.

ObjectiveObesity is a potentially modifiable risk factor for inflammatory bowel disease (IBD). We aimed to evaluate the body mass index (BMI) of those diagnosed with IBD early versus late in life in the context of age-adjusted background population.Design/methodPatients with a new diagnosis of IBD from 2000 to 2021 were included. Early-onset IBD was classified as age 2. Population data were obtained from community surveys.ResultsIncluded were 1573 patients (56.0%) with Crohn’s disease (CD) and 1234 (44.0%) with ulcerative colitis (UC). Overall, the median BMI at IBD diagnosis was 20 kg/m2(IQR 18–24) among those diagnosed at age 2(IQR 23.1–30.0) among those diagnosed at age ≥65 (rank-sum pConclusionPatients with IBD diagnosed at age

With the availability of hybrid DRAM and NVRAM memory on the memory bus of CPUs, a number of file systems on NVRAM have been designed and implemented. In this paper we present the design and implementation of a file system on NVRAM called DurableFS, which provides atomicity and durability of file operations to applications. It provides ACID properties to transactions involving multiple files. Due to the byte level random accessibility of memory, it is possible to provide these guarantees without much overhead. We use standard techniques like copy on write for data, and a redo log for metadata changes to build an efficient file system which provides durability and atomicity guarantees to transactions. Benchmarks on the implementation shows that there is only a 7% degradation in performance due to providing these guarantees.

Background and Aims Vedolizumab is an anti-α4β7 biologic approved for ulcerative colitis [UC] and Crohn’s disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission. Methods We performed a cross-sectional multi-centre study of inflammatory bowel disease [IBD] patients on maintenance vedolizumab. A homogeneous mobility shift assay [HMSA] was used to determine trough serum concentrations of vedolizumab and anti-drug antibodies [ATVs]. The primary outcome was corticosteroid-free clinical and biochemical remission defined as a composite of clinical remission, normalized C-reactive protein [CRP] and no corticosteroid use in 4 weeks. Secondary outcomes included corticosteroid-free endoscopic and deep remission. Vedolizumab concentrations were compared between patients in remission and with active disease. Logistic regression, adjusting for confounders, assessed the association between concentrations and remission. Results In total, 258 IBD patients were included [55% CD and 45% UC]. Patients in clinical and biochemical remission had significantly higher vedolizumab concentrations [12.7 µg/mL vs 10.1 µg/mL, p = 0.002]. Concentrations were also higher among patients in endoscopic and deep remission [14.2 µg/mL vs 8.5 µg/mL, p = 0.003 and 14.8 µg/mL vs 10.1 µg/mL, p = 0.01, respectively]. After controlling for potential confounders, IBD patients with vedolizumab concentrations >11.5 µg/mL were nearly 2.4 times more likely to be in corticosteroid-free clinical and biochemical remission. Only 1.6% of patients had ATVs. Conclusions In a large real-world cohort of vedolizumab maintenance concentrations, IBD patients with remission defined by objective measures [CRP and endoscopy] had significantly higher trough vedolizumab concentrations and immunogenicity was uncommon.

Restorative proctocolectomy with ileal pouch-anal anastomosis is an option for most patients with ulcerative colitis or familial adenomatous polyposis who require colectomy. Although the construction of an ileal pouch substantially improves patients' health-related quality of life, the surgery is, directly or indirectly, associated with various structural, inflammatory, and functional adverse sequelae. Furthermore, the surgical procedure does not completely abolish the risk for neoplasia. Patients with ileal pouches often present with extraintestinal, systemic inflammatory conditions. The International Ileal Pouch Consortium was established to create this consensus document on the diagnosis and classification of ileal pouch disorders using available evidence and the panellists' expertise. In a given individual, the condition of the pouch can change over time. Therefore, close monitoring of the activity and progression of the disease is essential to make accurate modifications in the diagnosis and classification in a timely manner.

Background Stress and depression are risk factors for inflammatory bowel disease (IBD) exacerbations. It is unknown if resilience, or one’s ability to recover from adversity, impacts disease course. The aim of this study was to examine the association between resilience and IBD disease activity, quality of life (QoL), and IBD-related surgeries. Methods We performed a cross-sectional study of IBD patients at an academic center. Patients completed the Connor-Davidson Resilience Scale questionnaire, which measures resilience (high resilience score ≥ 35). The primary outcome was IBD disease activity, measured by Mayo score and Harvey-Bradshaw Index (HBI). The QoL and IBD-related surgeries were also assessed. Multivariate linear regression was conducted to assess the association of high resilience with disease activity and QoL. Results Our patient sample comprised 92 patients with ulcerative colitis (UC) and 137 patients with Crohn disease (CD). High resilience was noted in 27% of patients with UC and 21.5% of patients with CD. Among patients with UC, those with high resilience had a mean Mayo score of 1.54, and those with low resilience had a mean Mayo score of 4.31, P < 0.001. Among patients with CD, those with high resilience had a mean HBI of 2.31, and those with low resilience had a mean HBI of 3.95, P = 0.035. In multivariable analysis, high resilience was independently associated with lower disease activity in both UC (P < 0.001) and CD (P = 0.037) and with higher QoL (P = 0.016). High resilience was also associated with fewer surgeries (P = 0.001) among patients with CD. Conclusions High resilience was independently associated with lower disease activity and better QoL in patients with IBD and fewer IBD surgeries in patients with CD. These findings suggest that resilience may be a modifiable factor that can risk-stratify patients with IBD prone to poor outcomes.

Background Mesalazine is the most commonly prescribed medication for mild to moderate ulcerative colitis. It is generally well tolerated with some reported side effects. Aim To summarise adverse drug events to mesalazine and recommend techniques for management. Furthermore, to determine if there is a dose-dependent relationship between high (>2.4 g/day) vs low dosing (≤2.4 g/day) and occurrence of adverse drug events. Methods A literature search for relevant studies from inception to 1 December 2017 of the MEDLINE database was conducted. Two reviewers screened all titles identified. Data obtained from randomised controlled trials was used to estimate incidence rates of each adverse event. Two reviewers independently assessed methodological risk of bias and performed data extraction. Results 3581 articles were initially considered. Of these, 3573 were screened, 622 reviewed and 91 included. Adverse events attributed to mesalazine included inflammatory reactions, pancreatitis, cardiotoxicity, hepatotoxicity, musculoskeletal complaints, respiratory symptoms, nephropathies and sexual dysfunction. There does not appear to be a dose-dependent relationship of mesalazine and occurrence of adverse events. Conclusion Patients on mesalazine should be monitored for worsening of ulcerative colitis and development of new onset organ dysfunction. High-dose mesalazine appears to have similar safety profile as low dose, and is not associated with greater risk of adverse events. Prior to placing a patient on mesalazine, baseline liver and renal function should be evaluated. Renal function should be periodically assessed, whereas other testing should be performed depending on development of symptoms.

In response to persistent and growing health disparities among racial and ethnic minority groups in the United States, health care institutions have started to enhance cultural competency education and training in both health care organizations and medical education. This effort to integrate culture into professional guidelines and training curricula has been consistent among the psychiatric workforce over the last few decades. While these efforts to address mental health disparities among racial and ethnic minority groups are welcomed, much more work is needed to integrate sociocultural education into medical training. This chapter describes the evolution of sociocultural medical education from teaching cultural competence to cultural humility, with its opportunities and challenges. Using a case-based approach, the authors propose general principles from existing curricula that can help psychiatric faculty design and teach sociocultural curricula for psychiatry trainees in diverse settings.

There are several adverse events that can occur in the setting of tumor necrosis factor-α inhibitor treatment for inflammatory bowel disease. The most common side effects include infection and malignancy. There are however several less frequent adverse events that can be classified as dermatologic, neurologic, cardiac, and hepatic. The aim of this review was to assist clinicians to recognize and manage these infrequent adverse events that occur during use of tumor necrosis factor-α antagonists.

In advanced stages of hepatic fibrosis, the liver sinusoidal endothelium transforms to vascular endothelium with accompanying expression of factor VIII-related antigen (FVIIIRAg), a phenotypic marker of vascular endothelial cells. Liver fibrosis has been shown to be associated with aging and was found to be prevalent in elderly cadavers. Using immunohistochemistry, we studied FVIIIRAg expression in the livers of elderly cadavers with progressive stages of fibrosis. The vascular endothelium of portal tracts and central veins was stained for FVIIIRAg, providing an internal positive control. The incidence of FVIIIRAg expression was low in the sinusoids of livers that showed minimal fibrosis or perisinusoidal fibrosis but was increased in livers with advanced fibrosis (i.e., septa formation, bridging fibrosis, and cirrhosis). FVIIIRAg positive sinusoidal endothelial cells were distributed in loose aggregates in the periportal, periseptal, and midlobular parenchyma and were found less frequently in the centrilobular area. FVIIIRAg immune deposits appeared patchy and discontinuous along the sinusoidal lining, likely representing focalized transformation of sinusoidal to vascular endothelium. There was a discrete localization of FVIIIRAg immunoreactivity in the foci of severe parenchymal fibrosis. Conclusion. FVIIIRAg is a reliable marker for detecting the transformation of sinusoidal to vascular endothelium in advanced liver fibrosis in elderly cadavers.

Numerous abstracts related to inflammatory bowel disease (IBD) are presented at national conferences in the USA. The overall rate of publication of these abstracts as complete manuscripts is unknown . Abstracts submitted to the 2010 American College of Gastroenterology (ACG), Advances in Inflammatory Bowel Diseases (AIBD), and the American Gastroenterological Association abstracts at Digestive Disease Week (DDW) were reviewed. Each abstract was reviewed manually by two authors for type of research, study design, patient population, and outcome. Both PubMed and Google were then searched to determine whether the abstract was published as a full manuscript within five years of the conference. Univariate and multivariate logistic regression analysis was carried out using Stata 14.1. In total, 872 abstracts were reviewed. 49% (426/872) were published as complete manuscripts within five years of the conference. The average length of time to publication was 1.87 years (range 0–5). 42% of abstracts from ACG, 58% from AIBD, and 23% from DDW were eventually published (p

Recently, power has emerged as a critical factor in designing components of storage systems, especially for power-hungry data centers. While there is some research into power-aware storage stack components, there are no systematic studies evaluating each component's impact separately. Various factors like workloads, hardware configurations, and software configurations impact the performance and energy efficiency of the system. This article evaluates the file system's impact on energy consumption and performance. We studied several popular Linux file systems, with various mount and format options, using the FileBench workload generator to emulate four server workloads: Web, database, mail, and fileserver, on two different hardware configurations. The file system design, implementation, and available features have a significant effect on CPU/disk utilization, and hence on performance and power. We discovered that default file system options are often suboptimal, and even poor. In this article we show that a careful matching of expected workloads and hardware configuration to a single software configuration—the file system—can improve power-performance efficiency by a factor ranging from 1.05 to 9.4 times.

Emerging byte-addressable, non-volatile memory like phase-change memory, STT-MRAM, etc. brings persistence at latencies within an order of magnitude of DRAM, thereby motivating their inclusion on the memory bus. According to some recent work on NVM, traditional file systems are ineffective and sub-optimal in accessing data from this low latency media. However, there exists no systematic performance study across different file systems and their various configurations validating this point. In this work, we evaluate the performance of various legacy Linux file systems under various real world workloads on non-volatile memory (NVM) simulated using ramdisk and compare it against NVM optimized file system — PMFS. Our results show that while the default file system configurations are mostly sub-optimal for NVM, these legacy file systems can be tuned using mount and format options to achieve performance that is comparable to NVM-aware file system such as PMFS. Our experiments show that the performance difference between PMFS and ext2/ext3 with execute-in-place (XIP) option is around 5% for many workloads (TPCC and YCSB). Furthermore, based on the learning from our performance study, we present few key file system features such as in-place update layout with XIP, and parallel metadata and data allocations, etc. that could be leveraged by file system designers to improve performance of both legacy and new file systems for NVM.

Differentiation of hematopoietic progenitor cells into T lymphocytes generally occurs in the unique environment of the thymus, a feature that has hindered efforts to model this process in the laboratory. We now report that thymic stromal cultures from rhesus macaques can support T-cell differentiation of human or rhesus CD34+ progenitor cells. Culture of rhesus or human CD34+ bone marrow-derived cells depleted of CD34+ lymphocytes on rhesus thymic stromal monolayers yielded CD3+CD4+CD8+, CD3+CD4+CD8-, and CD3+CD4-CD8+ cells after 10 to 14 days. In addition to classical T lymphocytes, a discrete population of CD3+CD8loCD16+CD56+ cells was detected after 14 days in cultures inoculated with rhesus CD34+ cells. CD3+ T cells arising from these cultures were not derived from contaminating T cells present in the CD34+ cells used to inoculate thymic stromal monolayers or from the thymic monolayers, as shown by labeling of cells with the lipophilic membrane dye PKH26. Expression of the recombinase activation gene RAG- 2, which is selectively expressed in developing lymphocytes, was detectable in thymic cultures inoculated with CD34+ cells but not in CD34+ cells before thymic culture or in thymic stromal monolayers alone. Reverse transcriptase-polymerase chain reaction analysis of T cells derived from thymic stromal cultures of rhesus and human CD34+ cells showed a polyclonal T-cell receptor repertoire. T-cell progeny derived from rhesus CD34+ cells cultured on thymic stroma supported vigorous simian immunodeficiency virus replication in the absence of exogenous mitogenic stimuli. Rhesus thymic stromal cultures provide a convenient means to analyze T-cell differentiation in vitro and may be useful as a model of hematopoietic stem cell therapy for diseases of T cells, including acquired immunodeficiency syndrome.

In the past storage vendors used different types of storage depending upon the type of workload. For example, they used Solid State Drives (SSDs) or FC hard disks (HDD) for online transaction, while SATA for archival type workloads. However, recently many storage vendors are designing hybrid SSD/HDD based systems that can satisfy multiple service level objectives (SLOs) of different workloads all placed together in one storage box, at better cost points. The combination is achieved by using SSDs as a read-write cache while HDD as a permanent store. In this paper we present an SLO based resource management algorithm that controls the amount of SSD given to a particular workload. This algorithm solves following problems: 1) it ensures that workloads do not interfere with each other 2) it ensure that we do not overprovision (cost wise) the amount of SSD allocated to a workload to satisfy its SLO (latency requirement) and 3) dynamically adjust SSD allocated in light of changing workload characteristics (i.e., provide only required amount of SSD). We have implemented our algorithm in a prototype Hybrid Store, and have tested its efficacy using many real workloads. Our algorithm satisfies latency SLOs almost always by utilizing close to optimal amount of SSD and saving 6–50% of SSD space compared to the naive algorithm.

Models of energy consumption and performance are necessary to understand and identify system behavior, prior to designing advanced controls that can balance out performance and energy use. This paper considers the energy consumption and performance of servers running a relatively simple file-compression workload. We found that standard techniques for system identification do not produce acceptable models of energy consumption and performance, due to the intricate interplay between the discrete nature of software and the continuous nature of energy and performance. This motivated us to perform a detailed empirical study of the energy consumption and performance of this system with varying compression algorithms and compression levels, file types, persistent storage media, CPU DVFS levels, and disk I/O schedulers. Our results identify and illustrate factors that complicate the system's energy consumption and performance, including nonlinearity, instability, and multi-dimensionality. Our results provide a basis for future work on modeling energy consumption and performance to support principled design of controllable energy-aware systems.

Data compression has been claimed to be an attractive solution to save energy consumption in high-end servers and data centers. However, there has not been a study to explore this. In this paper, we present a comprehensive evaluation of energy consumption for various file compression techniques implemented in software. We apply various compression tools available on Linux to a variety of data files, and we try them on server class and workstation class systems. We compare their energy and performance results against raw reads and writes. Our results reveal that software based data compression cannot be considered as a universal solution to reduce energy consumption. Various factors like the type of the data file, the compression tool being used, the read-to-write ratio of the workload, and the hardware configuration of the system impact the efficacy of this technique. In some cases, however, we found compression to save substantial energy and improve performance.

Background The median age of patients diagnosed with multiple myeloma (MM) is 69. Up to 60-80% of patients in this age group have hypertension (HTN) (Burt VL et al. Hypertension 1999), and are on anti-hypertensive medications. A standard treatment for MM is high dose melphalan (HDM) chemotherapy with autologous stem cell transplant (ASCT), which often results in gastrointestinal complications that can result in hypovolemia. The combined effect of anti-HTN agents and ASCT-related complications may result in blood pressure (BP) ranges that are precariously low. To date, the incidence of hypotension in the setting of ASCT for MM is unknown. In this case series of 102 patients who received ASCT for MM, we compare the characteristics of those who became hypotensive with those who did not. Methods We reviewed the charts of 102 consecutive MM/AL amyloid patients admitted for HDM chemotherapy with ASCT at Mount Sinai Hospital between May 2011 and June 2013. May 2011 was chosen as the date of inclusion because at this time, electronic medical records were implemented, allowing for detailed review of vital signs and other clinical data. Patients were classified into two groups. Patients included in group 1 demonstrated a drop in BP which was defined as meeting at least 1 of the following criteria: A) One or more anti-HTN medications were discontinued during ASCT B) Although normotensive on admission for ASCT, the median systolic or diastolic blood pressure (SBP or DBP) on date of discharge was ≤ 100 or 60 mm Hg respectively C) A decrease in SBP of ≥ 20 mm Hg was observed between admission and discharge Patients who did not meet any of the above criteria were classified into group 2. Baseline and peri- SCT characteristics of the two groups were compared using the chi square test. Results Of the 102 patients analyzed, 6 had AL amyloid and the remaining 96 had MM. 43 met at least one inclusion criteria for group 1 and the remaining 59 were classified as group 2. Specifically, of the patients in group 1, 18 met inclusion criteria A, 21 met inclusion criteria B, and 23 met inclusion criteria C. Among the patients in group 1 who met 2 criteria: 4 patients met criteria A and B, 4 patients met criteria A and C, and 9 patients met criteria B and C. Baseline characteristics including median age (64 and 63), gender distribution (55.8% and 47.5% females respectively), and a history of HTN (41.9% vs. 37.3%) were comparable in both groups (p>0.05). The median length of stay was 17 days in both groups. The incidence of gastrointestinal complications was comparable in both groups including diarrhea 72.1% vs. 62.7%, mucositis 14.0 % vs 8. 5%, and Clostridium difficile infection 9.3% vs. 6.8%. The ensuing weight loss in the 2 groups was also comparable 2.4 kg and 1.9 kg respectively. The incidence of infectious complications was similarly comparable in the 2 groups with fever 51.1 % vs 61% and bacteremia occurring in 7.0% vs 11.9%. Of the 43 patients in group 1, one patient had shock requiring ICU transfer for vasopressors in the setting of adrenal insufficiency and sepsis/bacteremia. Interestingly, of the 102 included patients, only 15 were reported to have clinically significant hypotension on the discharge summary. Of these 15 patients, 3 experienced transient hypotension, (i.e. for 1 -2 days,) with rapid normalization of pressure, and therefore, did not meet our inclusion criteria of persistent hypotension. Conclusions Although the incidence of hypotension in this series of MM patients undergoing ASCT was 42%, only 15% had documentation of this occurrence in the discharge summary. Interestingly, there were no statistically significant differences in the risk factors for ASCT associated hypotension in the 2 groups, including gastrointestinal and infectious complications. Given the unexpectedly high incidence of hypotension during ASCT, consideration should be given to the following: 1) Prior to SCT, anti-HTN medications should not be added (as is sometimes done for perioperative clearance) or titrated up; 2) During ASCT, anti-HTN medications may need to be discontinued; 3) Prior to discharge from ASCT, physical therapy/orthostatic evaluation and risk of falls from new relative hypotension needs to be assessed, especially in the setting of recovering thrombocytopenia. Although further studies are required, we hypothesize that fatigue, presyncopal events, and falls post SCT could be minimized with increased attention to HTN management peri ASCT. Disclosures: Chari: Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Millenium : Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees.