Rishi, Abdul

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS.

Key messageComplete lung collapse associated with sarcoidosis is exceedingly rare. Although lymphoma should be ruled out when patients with mediastinal lymphadenopathy develop lung collapse, sarcoidosis should be considered in the differential, especially when associated with fibrosing mediastinitis.

Abstract Background: It is well established that the incidence of skin cancers in patients with CLL are significantly elevated compared to age- and sex- matched controls. However, little is known about the characteristics of CLL patients who develop skin cancer. Herein, we evaluate the associations of CLL clinical and prognostic characteristics, along with UV radiation exposure, with risk of first skin cancer following CLL diagnosis. Methods: Newly diagnosed CLL patients from Minnesota, Iowa, and Wisconsin were enrolled in the Mayo Clinic case-control study from 2002-2015 and systematically followed in the Iowa/Mayo Lymphoma SPORE. Clinical and prognostic CLL data were obtained from the Mayo Clinic CLL database, and skin cancer clinical data were abstracted from medical records using a standard protocol. The CLL international prognostic index (CLL-IPI) was computed using a weighted average of five independent CLL prognostic factors (IGHV mutational status, serum b2-microglobulin, Rai stage, age, and FISH 17p deletion/TP53 status). Self-reported history of midday sun exposure at various ages (birth to age 12; 13 to 21 years; 22 to 40 years, and 41+ years) was obtained from a risk factor questionnaire. For each age, we asked the extent of mid-day sun as: practically no exposure (under 3 hours per week), little exposure (4-7 hours per week), moderate exposure (8 to 14 hours per week) and extensive exposure (15+ hours per week). Midday sun exposure was modeled as an ordinal covariate. To evaluate associations with risk of skin cancer following CLL diagnosis, we calculated time from date of CLL diagnosis to date of first skin cancer, death, or last known follow-up. We used Cox regression analysis to estimate hazard ratios (HRs) and 95% CIs. CLL treatment was considered a time-dependent covariate. Results: Among 846 CLL patients enrolled, the median age at diagnosis was 63 years (range 28-91), 68% were male, 7% had Rai stage III-IV at diagnosis. Based on the CLL-IPI, 42% were categorized as low risk, 33% as intermediate risk, and 25% as high or very-high risk. 109 CLL cases (13%) had one or more reported skin cancers at or prior to CLL diagnosis. Melanoma was observed in 19 (2%) cases and non-melanoma was in 90 (11%) cases. At a median follow-up of 7 years from CLL diagnosis, 165 patients (20%) had one or more skin cancers after CLL diagnosis. Among these patients, 49 had skin cancer before CLL diagnosis. The most frequent skin cancer was squamous cell carcinoma (59%), followed by basal cell (31%), melanoma (5%), and Merkel cell (1%). 552 (65%) of the 846 patients returned a questionnaire. Significant associations of clinical and prognostic characteristics with risk of first skin cancer were observed for age (HR=1.35 per 10 year increase, 95% CI=1.17-1.56, P<0.001), male sex (HR=1.38, 95% CI 0.98-1.96, p=0.07), prior history of skin cancer (HR=4.19, 95% CI=2.98-5.88, P<0.001), and CLL-IPI (HR=1.26, 95% CI= 1.03-1.54, P=0.026, after adjusting for age, sex, and prior skin cancer). Of note, the risk of first skin cancer in those CLL patients categorized as very high via CLL-IPI had 2.28 fold risk (95% CI 1.02-5.11). Midday sun exposures for each of the ages considered showed no evidence of association with risk of first skin cancer (all P>0.05). 50 CLL patients were treated prior to first skin cancer following CLL diagnosis; we observed no evidence of association between treatment and risk of first skin cancer (HR=1.44, 95% CI= 0.93-1.92, P=0.12). Conclusion: CLL patients who are at an increased risk of skin cancer following CLL diagnosis are those who either have had a prior history of skin cancer or a more aggressive CLL disease at diagnosis, according to CLL IPI. Routine skin cancer screening is currently recommended for CLL patients. Our data suggest that more frequent screening would be particularly important among patients with aggressive CLL and who have a prior history of skin cancer. Unexpectedly, we found no evidence of association of skin cancer risk with UV radiation following CLL diagnosis or with CLL treatment. Further investigation is needed to determine whether other factors increase the risk of skin cancer following CLL diagnosis. Disclosures Shanafelt: Genentech: Research Funding; GlaxoSmithkKine: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Cephalon: Research Funding; Pharmacyclics: Research Funding; Hospira: Research Funding.

Abstract We and others previously demonstrated an increased risk of monoclonal gammopathy of undetermined significance (MGUS) in first-degree relatives of multiple myeloma (MM) and MGUS patients, underscoring a familial component to this disease. However, MM is known to be a collection of cytogenetically distinct diseases, with 40-50% of MM cases having a reciprocal translocation involving the IgH locus on chromosome 14q32 and in many of the remaining patients, trisomies. In a small proportion of cases, both IgH abnormalities and trisomies are found in the same clone. These MM cytogenetic subtypes are associated with differential prognosis. Whether there are differences in familial risk by cytogenetic subtypes is not known. Patients with MM were recruited from the Mayo Clinic Hematology practice in Rochester, Minnesota (MN) between 2005 and 2015. Serum samples were collected from first-degree relatives and subjected to electrophoresis and immunofixation for MGUS determination. Age- and sex-specific rates of MGUS from the population-based Olmsted County, MN, prevalence study were used as expected rates for the calculation of risk ratios (RRs) for comparisons of first-degree relatives. Cytogenetic subtypes were classified by FISH testing performed in the clinic and categorized into groups defined by IgH translocation , trisomy, intermediate/ high-risk disease (t(4;14), t(14;16), t(14;20), and del17p). Further, the distribution of cytogenetic subtypes was compared between MM cases with and without evidence of MGUS in first degree relatives using Chi square tests. Analyses were also subset to MM probands diagnosed in MN. There were a total of 442 MM probands, with 1235 first-degree relatives recruited and eligible for the study. MGUS was detected in 78 relatives, for an age- and sex-adjusted prevalence of 6.1% (4.7%-7.5%). Analyses comparing prevalence of MGUS in first degree relatives to population-based rates from Olmsted County showed a 2.5-fold (95% CI=1.9-3.0) increased prevalence. When performing analyses among MN probands only (RR=2.9; 95% CI=2.1-3.8), results were similar. Of the 442 probands, 310 had FISH performed on plasma cells (identified by cIG staining; cIg-FISH) at diagnosis. Of these cases, 49% had a trisomy, 23% had an IgH translocation, and 9% had both. Although the proportion of trisomies and IgH translocations were 4-6% higher among MM probands with a relative with MGUS compared to those without, these differences were not statistically significant (Table 1). MM probands with a first degree relative with MGUS also had a similar proportion of cytogenetic subtypes that are considered of intermediate or high risk compared to those MM without a family history (26.9% vs 25.2%) (p=0.79) (Table 1). When restricted to MM probands from MN, results remained non-statistically significant (Table 1). We showed an increased risk of MGUS in first-degree relatives of MM cases, implying shared environment and/or genetics underlying this malignancy. However, we did not find an association between family history of MGUS in MM probands and the cytogenetic subtypes examined. Larger cohorts are needed to examine if a relationship exists between cytogenetic subtypes of MM and familial risk. Disclosures Kumar: Noxxon Pharma: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; AbbVie: Research Funding; Onyx: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Glycomimetics: Consultancy; Kesios: Consultancy; Janssen: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Research Funding; BMS: Consultancy.

AbstractBackgroundRumination syndrome is a functional gastrointestinal disorder characterized by effortless and repetitive regurgitation of recently ingested food from the stomach to the oral cavity followed by either re‐swallowing or spitting. Rumination is thought to occur due to a reversal of the esophagogastric pressure gradient. This is achieved by a coordinated abdominothoracic maneuver consisting of a thoracic suction, crural diaphragm relaxation and an increase in intragastric pressure. Careful history is important in the diagnosis of rumination syndrome; patients often report “vomiting” or “reflux” and the diagnosis can therefore be missed. Objective testing is available with high resolution manometry or gastroduodenal manometry. Increase in intra‐gastric pressure followed by regurgitation is the most important characteristic to distinguish rumination from other disorders such as gastroesophageal reflux. The mainstay of the treatment of rumination syndrome is behavioral therapy via diaphragmatic breathing in addition to patient education and reassurance.PurposeThe purpose of this review was to critically appraise recent key developments in the pathophysiology, diagnosis and therapy for rumination syndrome. A literature search using OVID (Wolters Kluwer Health, New York, NY, USA) to examine the MEDLINE database its inception until May 2016 was performed using the search terms “rumination syndrome,” “biofeedback therapy,” and “regurgitation.” References lists and personal libraries of the authors were used to identify supplemental information. Articles published in English were reviewed in full text. English abstracts were reviewed for all other languages. Priority was given to evidence obtained from randomized controlled trials when possible.

ABSTRACTObjectives:Guidelines for diagnosing celiac disease (CD) recommend initial testing with a highly sensitive serologic test for anti–tissue transglutaminase immunoglobulin A antibodies (tTG IgA). When the probability of CD is high, IgA deficiency should be considered. The 2 approaches to address this include measuring “both tTG IgA and tTG IgG” or measuring “total IgA.” We aim to assess the utility of an isolated positive tTG IgG result in diagnosing CD.Methods:We conducted a retrospective review of patients undergoing serologic testing for CD from January 1997 to June 2014. Patients with positive tTG IgG and negative tTG IgA were included. Moreover, all patients who had any other positive CD‐specific serologic findings were excluded. Demographics, clinical presentation, tests, and biopsy results were recorded.Results:The indication for checking celiac serology was gastrointestinal symptoms in 172 of 233 patients, iron deficiency anemia in 12, and high‐risk screening in 48. Small bowel biopsy was performed in 178 patients (77%); 160 had normal results and 18 had histologic changes suggestive of enteropathy. Nine patients had increased intraepithelial lymphocytes, and 9 had partial villous atrophy. Only 6 cases of CD were, however, confirmed. The utility of isolated tTG IgG in diagnosis of CD was low at 3% (6/178).Conclusion:In this cohort of patients, the utility of isolated tTG IgG in diagnosing CD was low at 3%.

Abstract Retroperitoneal abscess is an uncommon infection that is associated with high morbidity. Early diagnosis is imperative; however, due to its insidious onset and subtle presentation, the diagnosis is often missed. We report a case of a retroperitoneal abscess caused by Streptococcus mitis which is usually not implicated as a serious pathogen, at least in immunocompetent patients.

SummaryBackgroundOlmesartan‐associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue‐like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil.AimTo determine the mechanistic similarities of OAE with coeliac sprue.MethodsDuodenal biopsies were extracted from OAE patients before (n = 11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven ‘on/off’ paired samples. Formalin‐fixed biopsies were stained for CD8, CD4, FoxP3, IL‐15R and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL‐15, IL‐15R and ZO‐1.ResultsIn the ‘on olmesartan medoxomil’ duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T‐cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco‐2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO‐1, a tight junction protein, is disrupted in olmesartan medoxomil‐treated Caco‐2 cells.ConclusionsOlmesartan‐associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.

SummaryAll vertebrates contain a diverse collection of commensal, symbiotic and pathogenic microorganisms, such as bacteria, viruses and fungi, on their various body surfaces, and the ecological community of these microorganisms is referred to as the microbiota. Mucosal sites, such as the intestine, harbour the majority of microorganisms, and the human intestine contains the largest community of commensal and symbiotic bacteria. This intestinal community of bacteria is diverse, and there is a significant variability among individuals with respect to the composition of the intestinal microbiome. Both genetic and environmental factors can influence the diversity and composition of the intestinal bacteria with the predominant environmental factor being diet. So far, studies have shown that diet‐dependent differences in the composition of intestinal bacteria can be classified into three groups, called enterotypes. Other environmental factors that can influence the composition include antibiotics, probiotics, smoking and drugs. Studies of monozygotic and dizygotic twins have proven that genetics plays a role. Recently, MHC II genes have been associated with specific microbial compositions in human infants and transgenic mice that express different HLA alleles. There is a growing list of genes/molecules that are involved with the sensing and monitoring of the intestinal lumen by the intestinal immune system that, when genetically altered, will significantly alter the composition of the intestinal microflora. The focus of this review will be on the genetic factors that influence the composition of the intestinal microflora.