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Background: Down syndrome (DS) is associated with increased risk for Alzheimer’s disease (AD). In neurotypical individuals, clinical AD is preceded by reduced resting state functional connectivity in the default mode network (DMN), but it is unknown whether changes in DMN connectivity predict clinical onset of AD in DS. Objective: Does lower DMN functional connectivity predict clinical onset of AD and cognitive decline in people with DS? Methods: Resting state functional MRI (rsfMRI), longitudinal neuropsychological, and clinical assessment data were collected on 15 nondemented people with DS (mean age = 51.66 years, SD = 5.34 years, range = 42-59 years) over four years, during which 4 transitioned to dementia. Amyloid-β (Aβ) PET data were acquired on 13 of the 15 participants. Resting state fMRI, neuropsychological, and clinical assessment data were also acquired on an independent, slightly younger unimpaired sample of 14 nondemented people with DS (mean age = 44.63 years, SD = 7.99 years, range = 38–61 years). Results: Lower functional connectivity between long-range but not short-range DMN regions predicts AD diagnosis and cognitive decline in people with DS. Aβ accumulation in the inferior parietal cortex is associated with lower regional DMN functional connectivity. Conclusion: Reduction of long-range DMN connectivity is a potential biomarker for AD in people with DS that precedes and predicts clinical conversion.

Background: \ud Reports of HLA incompatible (HLAi) kidney transplant outcomes are inconclusive, especially in the context of lower level Donor Specific Antibodies (DSA).\ud \ud Methods: \ud Multi-centre national cohort study of HLAi kidney transplant recipients matched in 1:2 ratio with HLA compatible (HLAc) kidney transplant recipients. HLAi defined as DSA identified by Luminex. Antibody mediated rejection (AMR) and transplant-survival were analysed using Kaplan-Meier plots. Propensity score (PS) matching was used to compare recipient and transplant survival between groups.\ud \ud Results: \ud We included 61 HLAi and 122 HLAc recipients; mean age 46 years; 60% female. MFIT0: 3327 (IQR 1352 – 6458), 23 (38%) were Flow cytometry crossmatch positive (FC-XMPOS). DSAPOS/FC-XMPOS transplantation carried an increased risk of AMR at 1 year (52%) compared to DSAPOS/FC-XMNEG (27%) and HLAc (0%). Unadjusted death censored graft loss at 3 years was 13% (HLAi) and 8% (HLAc). Three-year patient survival was 95% in HLAc, 84% in DSAPOS/FC-XMNEG and 69% in DSAPOS/FC-XMPOS recipients; 58% of HLAi deaths were infection-related. HLA incompatibility was associated with a decreased 3-year survival in our PS-matched cohort.\ud \ud Conclusion: \ud In kidney transplantation, DSA and positive FC-XM carries an increased risk of AMR. Despite inferior transplant and survival outcomes compared to HLAc transplantation, it remains a realistic option for highly sensitised patients facing prolonged waiting times and reduced survival on dialysis.

HLA-DR, an MHC class II molecule that mediates antigen presentation, is a favourable prognostic indicator in colorectal cancer (CRC). However, the dynamics and location of HLA-DR expression during CRC development are unclear. We aimed to define HLA-DR expression by immunohistochemistry in colorectal epithelium and stromal tissue at different stages of cancer development, assessing non-neoplastic colorectal adenocarcinoma–adjacent tissue, adenomas and carcinoma tissues, and to associate HLA-DR levels with clinical outcomes. Patients with higher than median HLA-DR expression survived at least twice as long as patients with lower expression. This association was significant for HLA-DR staining in the colorectal carcinoma epithelium (n = 152, p = 0.011, HR 1.9, 95% CI 1.15–3.15) and adjacent non-neoplastic epithelium (n = 152, p n = 63, p = 0.015, HR 3.6, 95% CI 1.279–10.25) and stroma (n = 63, p = 0.018, HR 5.07, 95% CI 1.32–19.49). HLA-DR was lower in carcinoma tissue compared to matched adenomas (n = 35), in epithelium (p p n = 101) compared to early stage (n = 105), in epithelium (p p p

Summary Background Pneumocystis pneumonia (PCP) is an opportunistic infection occurring in renal transplant patients. Over a 14-month period an increase in PCP cases was identified among our renal transplant cohort. Aim The outbreak population was studied to identify potential risk factors for the development of PCP. Methods A retrospective analysis of hospital records was carried out, with each case being matched with two case-linked controls. Information was collected on patient demographics, laboratory tests, and hospital visits pre and post development of infection. Findings No patients were receiving PCP prophylaxis at the time of infection and mean time from transplantation to developing PCP was 4.7 years (range: 0.51–14.5). The PCP group had a significantly lower mean estimated glomerular filtration rate than the control group (29.3 mL/min/1.73 m2 vs 70 mL/min−1 (P = 0.0007)). Three patients were treated for active cytomegalovirus (CMV) infection prior to PCP diagnosis and two had active CMV at the time of diagnosis compared to none in the control group (P = 0.001). Those who developed PCP were more likely to have shared a hospital visit with another patient who went on to develop PCP; 37% of clinic visits vs 19% (P = 0.014). Conclusion This study highlights the ongoing risk of opportunistic infection several years after transplantation and adds weight to potential person-to-person Pneumocystis jirovecii transmission. Risk factors have been identified which may highlight those most at risk, enabling targeted rather than blanket long-term PCP prophylaxis.

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in general, non-transplant setting, can predict risk of, and time to post-transplant skin cancer. Genetic variants, reaching pre-defined p-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) non-transplant GWAS. Using these genome-wide association studies, BCC and SCC PRS were calculated for each sample across three European-ancestry renal-transplant cohorts (n=889) and tested as predictors of case:control status and time to NMSC post-transplant. BCC PRS calculated at p-value threshold 1x10 was the most significant predictor of case:control status of NMSC post-transplant (OR=1.65; adjusted P=0.0008; AUC(full model adjusted for clinical predictors and PRS)=0.81). SCC PRS at p-value threshold 1x10 was the most significant predictor of time to post-transplant NMSC (adjusted P=8.15x10 ; HR=1.42, concordance (full model)=0.74). PRS of non-transplant NMSC is predictive of case:control status and time to NMSC post-transplant. These results are relevant to how genomics can risk stratify patients to help develop personalised treatment regimens. This article is protected by copyright. All rights reserved.

Emerging evidence indicates that the predictability of signals early in life may influence the developing brain. This study examines links between a novel indicator of maternal mood dysregulation, mood entropy, and child neurodevelopmental outcomes. Associations between prenatal maternal mood entropy and child neurodevelopment were assessed in 2 longitudinal cohorts. Maternal mood was measured several times over pregnancy beginning as early as 15 weeks' gestation. Shannon's mood entropy was applied to distributions of mothers' responses on mood questionnaires. Child cognitive and language development were evaluated at 2 and 6-9 years of age. Higher prenatal maternal mood entropy was associated with lower cognitive development scores at 2 years of age and lower expressive language scores at 6-9 years of age. These associations persisted after adjusting for maternal pre and postnatal mood levels and for other relevant sociodemographic factors. Our findings identify maternal mood entropy as a novel predictor of child neurodevelopment. Characterizing components of maternal mood in addition to level of severity or valence may further our understanding of specific processes by which maternal mood shapes child development. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Objective The aim of this study is to examine the effect of postoperative chemotherapy on survival in patients with stage II or III rectal adenocarcinoma who undergo neoadjuvant chemoradiation (CRT) and surgical resection. Methods A retrospective review of the National Cancer Database (NCDB) from 2006 to 2013 was performed. Cases were analyzed based on pathologic complete response (pCR) status and use of adjuvant therapy. The Kaplan-Meier method was used to estimate overall survival probabilities. Results 23,045 cases were identified, of which 5832 (25.31%) achieved pCR. In the pCR group, 1513 (25.9%) received adjuvant chemotherapy, and in the non-pCR group, 5966 (34.7%) received adjuvant therapy. In the pCR group, five-year survival probability was 87% (95% CI 84%–89%) with adjuvant therapy and 81% (95% CI 79%–82%) without adjuvant therapy. In the non-pCR group, five-year survival probability was 78% (95% CI 76%–79%) with adjuvant therapy and 70% (95% CI 69%–71%) without adjuvant therapy. In the non-pCR and node-negative subgroup (ypN-), five-year survival probability was 86% (95% CI 84%–88%) with adjuvant therapy and 76% (95% CI 74%–77%) without adjuvant therapy. In the non-pCR and node-positive subgroup (ypN+), five-year survival probability was 67% (95% CI 65%–70%) with adjuvant therapy and 60% (95% CI 58%–63%) without adjuvant therapy. Conclusions Adjuvant chemotherapy in stage II or III rectal adenocarcinoma is associated with increased five-year survival probability regardless of pCR status. We observed similar survival outcomes among non-pCR ypN- treated with adjuvant chemotherapy compared with patients achieving pCR treated with adjuvant chemotherapy.

Background The American Academy of Pediatrics (AAP) recommends shared reading beginning as soon as possible after birth to promote healthy development. Shared reading quality can strongly influence outcomes, especially in children from low-SES households. Dialogic reading is a method developed to enhance verbal interactivity and engagement through book sharing, advocated by the AAP and clinic-based programs such as Reach Out and Read. There is no brief, validated, caregiver report measure of dialogic reading or shared reading quality currently available. Methods This cross-sectional study involved 49 healthy mother-child dyads (mean child age 4.5 yrs., SD = 0.6 yrs.) from 2 separate MRI-based studies. The DialogPR was administered by trained research coordinators following MRI, along with the READ subscale of the validated StimQ-P measure of home cognitive environment. The DialogPR consists of eight items developed in consultation with experts in early literacy, based on the PEER/CROWD dialogic reading conceptual model. Estimated reading level is 6th grade. Descriptive statistics were computed at both the item and scale levels. Modern theory Rasch methods were used to analyze all eight DialogPR items along with preliminary estimates of reliability and validity. Results Our combined sample involved 15 boys and 34 girls, and was diverse in terms of age, household income, and maternal education. DialogPR administration time was less than 2 min, with no problems reported. The DialogPR demonstrated strong internal consistency and reliability (Cronbach’s alpha = 0.82), and criterion-related validity with the StimQ-P READ (Spearman’s rho coefficient = 0.53). Rasch analysis revealed strong psychometric properties in terms of reliability, variability in item difficulty, and inter-item and item-measure correlations. Conclusions Preliminary evidence suggests that the DialogPR may be an efficient means to assess shared reading quality and dialogic reading via caregiver report for clinical and research purposes, warranting further investigation.

Background The effectiveness of thoracic epidural analgesia (EA) vs conventional IV analgesia (IA) after minimally invasive surgery is still unproven. We designed a randomized controlled trial comparing EA with IA after minimally invasive colorectal surgery. Study Design A total of 87 patients who underwent minimally invasive colorectal procedures at a single institution between 2011 and 2014 were enrolled. Eight patients were excluded and 38 were randomized to EA and 41 to IA. Pain was assessed with the Visual Analogue Scale and quality of life with the Overall Benefit of Analgesia Score daily until discharge. Results Mean age was 57 ± 14 years, 43% of patients were female, and mean BMI was 28.6 ± 6 kg/m 2 . The 2 groups were similar in demographic characteristics and distribution of diagnoses and procedures. Epidural analgesia had a higher incidence of hypotensive systolic blood pressure ( 0.05). Epidural and IA had equivalent mean lengths of stay (4 ± 3 days vs 4 ± 3 days), daily Visual Analogue Scale scores (2.4 ± 2.0 vs 3.0 ± 2.0), and Overall Benefit of Analgesia Scores (3.2 ± 2.0 vs 3.2 ± 2.0), and similar time to start oral diet (2.8 ± 2 days vs 2.2 ± 1 days). Epidural analgesia patients used a higher total dose of narcotics (147.5 ± 192.0 mg vs 98.1 ± 112.0 mg; p > 0.05). Epidural and IV analgesia had equivalent total hospital charges ($144,991 ± $67,636 vs $141,339 ± $75,579; p > 0.05). Conclusions This study indicates that EA has no added clinical benefit in patients undergoing minimally invasive colorectal surgery. A trend toward higher total narcotics use and complications with EA was demonstrated.

Background A study to investigate transmission of classical scrapie via goat milk was carried out in sheep: firstly, lambs were challenged orally with goat scrapie brain homogenate to confirm transmission of scrapie from goats to sheep. In the second study phase, milk from scrapie-infected goats was fed to lambs. Lambs were selected according to their prion protein gene (PRNP) genotype, which was either VRQ/VRQ or ARQ/ARQ, with or without additional polymorphisms at codon 141 (FF141, LF141 or LL141) of the ovine PRNP. This report describes the clinical, pathological and molecular phenotype of goat scrapie in those sheep that progressed to clinical end-stage. Results Ten sheep (six VRQ/VRQ and four ARQ/ARQ, of which three FF141 and one LL141) challenged with one of two scrapie brain homogenates, and six pairs of sheep (ARQ, of which five LL141 and seven LF141) fed milk from six different goats, developed clinical disease, which was characterised by a pruritic (all VRQ/VRQ and LL141 sheep) or a non-pruritic form (all LF141 and FF141 sheep). Immunohistochemical (IHC) examination revealed that the pattern of intra- and extracellular accumulation of disease-associated prion protein in the brain was also dependent on PRNP polymorphisms at codon 141, which was similar in VRQ and LL141 sheep but different from LF141 and FF141 sheep. The influence of codon 141 was also seen in discriminatory Western blot (WB), with LF141 and FF141 sheep showing a bovine spongiform encephalopathy-like profile (diminished reactivity with P4 antibody) on brain tissue. However, discriminatory WB in lymphoid tissues, and IHC pattern and profile both in lymphoid and brain tissue was consistent with classical scrapie in all sheep. Conclusions This study provided further evidence that the clinical presentation and the pathological and molecular phenotypes of scrapie in sheep are influenced by PRNP polymorphisms, particularly at codon 141. Differences in the truncation of disease-associated prion protein between LL141 sheep and those carrying the F141 allele may be responsible for these observations. Electronic supplementary material The online version of this article (doi:10.1186/s12917-017-1036-1) contains supplementary material, which is available to authorized users.

An increasing body of evidence suggests that bone marrow–derived myeloid cells play a critical role in the pathophysiology of pulmonary hypertension (PH). However, the true requirement for myeloid cells in PH development has not been demonstrated, and a specific disease-promoting myeloid cell population has not been identified. Using bone marrow chimeras, lineage labeling, and proliferation studies, we determined that, in murine hypoxia-induced PH, Ly6Clo nonclassical monocytes are recruited to small pulmonary arteries and differentiate into pulmonary interstitial macrophages. Accumulation of these nonclassical monocyte–derived pulmonary interstitial macrophages around pulmonary vasculature is associated with increased muscularization of small pulmonary arteries and disease severity. To determine if the sensing of hypoxia by nonclassical monocytes contributes to the development of PH, mice lacking expression of hypoxia-inducible factor-1α in the Ly6Clo monocyte lineage were exposed to hypoxia. In these mice, vascular remodeling and PH severity were significantly reduced. Transcriptome analyses suggest that the Ly6Clo monocyte lineage regulates PH through complement, phagocytosis, Ag presentation, and chemokine/cytokine pathways. Consistent with these murine findings, relative to controls, lungs from pulmonary arterial hypertension patients displayed a significant increase in the frequency of nonclassical monocytes. Taken together, these findings show that, in response to hypoxia, nonclassical monocytes in the lung sense hypoxia, infiltrate small pulmonary arteries, and promote vascular remodeling and development of PH. Our results demonstrate that myeloid cells, specifically cells of the nonclassical monocyte lineage, play a direct role in the pathogenesis of PH.

Background: In Scotland, standard maintenance immunosuppression following kidney transplantation consists of mycophenolate (MPA), tacrolimus and prednisolone irrespective of recipient age. We analysed the tolerability of this immunosuppression regimen and the association with transplant outcomes. Methods: A national, multicentre retrospective analysis of patients transplanted in 2015 and 2016, comparing graft function, acute rejection, significant infection rates and immunosuppression dosing between patients aged 18-59 years (Group 1) and ≥60 years (Group 2). Results: Of the 490 patients, 26% were aged ≥60 years. Acute rejection (AR) rates at 1 year were 15% and 11% in Group 1 and 2 respectively. Full dose MPA was poorly tolerated with 53% in Group 1 and 77% in Group 2 requiring dose reduction or cessation. Female gender and age ≥60 years were independent predictors for MPA dose changes. One year following MPA dose reduction AR risk was low (5%) in Group 2, however those remaining on full dose MPA had a 79% increased rate of serious infections. Conclusion: The majority of renal transplant recipients aged ≥60 fail to tolerate full dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate.

Background & Aims: KH-type splicing regulatory protein (KHSRP) is a multifunctional nucleic acid binding protein. KHSRP regulates transcription, mRNA decay and translation, and miRNA biogenesis. These distinct functions are associated with key aspects of cancer cell biology: inflammation and cell-fate determination. However, the role KHSRP plays in colorectal cancer (CRC) tumorigenesis remains largely unknown. Methods: We investigated the oncogenic role of KHSRP in CRC using a combination of in silico analysis of large datasets, ex vivo analysis of protein expression in patient samples, and mechanistic studies using in vitro models of CRC. Results: KHSRP was expressed in the epithelial and stromal compartments of both primary and metastatic tumors. Elevated KHSRP expression was found in tumor versus matched normal tissue in a cohort of 62 patients. This finding was validated in larger independent cohorts in silico. KHSRP expression was a prognostic indicator of worse overall survival (HR=3.74, 95% CI = 1.43-22.97, p=0.0138). Mechanistic data in CRC cell line models supported a role of KHSRP in driving epithelial cell proliferation in both a primary and metastatic setting, through control of the G1/S transition. Additionally, epithelial KHSRP was involved in promoting a pro-angiogenic extracellular environment, as well as regulating the secretion of oncogenic proteins involved in diverse cellular processes such as migration and response to cellular stress. Conclusion: Our study has uncovered novel mechanistic-based data on the tumor- promoting effects of KHSRP in CRC.

Barrett&rsquo, s esophagus (BE), a chronic inflammatory condition, is the leading risk factor for esophageal adenocarcinoma (EAC). In inflammation to cancer pathways, oxidative stress profiles have been linked to cancer progression. However, the relevance of oxidative stress profiles along the BE-disease sequence remains to be elucidated. In this study, markers of oxidative stress, DNA adducts (8-oxo-dG) and lipoperoxidation (4-HNE), and markers of proliferation (Ki67) were measured in patient biopsies representing the BE-disease sequence. Differences in expression of these markers in Barrett&rsquo, s patients with cancer-progression and non-progression were examined. Proliferation was reduced in Barrett&rsquo, s specialized intestinal metaplasia (SIM) compared with EAC (p &lt, 0.035). Correcting for cell proliferation levels, a confounding factor, linked to oxidative stress profiles, SIM demonstrated increased levels of 8-oxo-dG and 4-HNE (p &lt, 0.05) compared with EAC. Longitudinal analysis of Barrett&rsquo, s patients demonstrated decreased levels of 8-oxo-dG in SIM cancer progression (p &lt, 0.05). BE is an environment of increased oxidative stress and inflammation. Patients with progressive disease demonstrated reduced oxidative stress levels in 8-oxo-dG. Perhaps these alterations facilitate Barrett&rsquo, s progression, whereas in non-progressive disease, cells follow the rules of increased oxidative stress ultimately triggers cell apoptosis, thereby preventing propagation and survival.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media from explanted tissue was used to model the effects of the tumor microenvironment on MAIT cell function. Associations were assessed between MAIT cell frequency, circulating inflammatory markers, and clinical parameters to elucidate the role of MAIT cells in inflammation driven cancer. MAIT cells were decreased in BO and OAC blood compared to healthy controls, but were increased in oesophageal tissues, compared to BO-adjacent tissue, and remained detectable after neo-adjuvant treatment. MAIT cells in tumors expressed CD8, PD-1, and NKG2A but lower NKG2D than BO cohorts. MAIT cells produced less IFN-γ and TNF-α in the presence of tumor-conditioned media. OAC cell line viability was reduced upon exposure to expanded MAIT cells. Serum levels of chemokine IP-10 were inversely correlated with MAIT cell frequency in both tumors and blood. MAIT cells were higher in the tumors of node-negative patients, but were not significantly associated with other clinical parameters. This study demonstrates that OAC tumors are infiltrated by MAIT cells, a type of CD8 T cell featuring immune checkpoint expression and cytotoxic potential. These findings may have implications for immunotherapy and immune scoring approaches.

Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables.

Amorphous silicon dioxide nanoparticles (SiNPs) are ubiquitous, and they are currently found in cosmetics, drugs, and foods. Biomedical research is also focused on using these nanoparticles as drug delivery and bio-sensing platforms. Due to the high potential for skin exposure to SiNPs, research into the effect of topical exposure on both healthy and inflammatory skin models is warranted. While we observe only minimal effects of SiNPs on healthy mouse skin, there is an immunomodulatory effect of these NPs in a model of allergic contact dermatitis. The effect appears to be mediated partly by keratinocytes and results in decreases in epidermal hyperplasia, inflammatory cytokine release, immune cell infiltration, and a subsequent reduction in skin swelling. Additional research is required to further our mechanistic understanding and to validate the extent of this immunomodulatory effect in human subjects in order to assess the potential prophylactic use of SiNPs for treating allergic skin conditions.

Overexpression of the amyloid precursor protein (APP)gene on chromosome 21 in Down syndrome (DS) has been linked to increased brain amyloid levels and early-onset Alzheimer’s disease (AD). An elderly man with phenotypic DS and partial trisomy of chromosome 21 (PT21) lacked triplication of APP affording an opportunity to study the role of this gene in the pathogenesis of dementia. Multidisciplinary studies between ages 66–72 years comprised neuropsychological testing, independent neurological exams, amyloid PET imaging with 11C-Pittsburgh compound-B (PiB), plasma Amyloid-β(Aβ)measurements and a brain autopsy examination. The clinical phenotype was typical for DS and his intellectual disability was mild in severity. His serial neuropsychological test scores showed less than a 3% decline as compared to high functioning individuals with DS who developed dementia wherein the scores declined 17–28% per year. No dementia was detected on neurological examinations. On both PiB-PET scans, the patient with PT21 had lower PiB standard uptake values than controls with typical DS or sporadic AD. Plasma Aβ42 was lower than values for demented or non -demented adults with DS. Neuropathological findings showed only a single neuritic plaque and neurofibrillary degeneration consistent with normal aging but not AD. Taken together the findings in this rare patient with PT21 confirm the obligatory role of APPin the clinical, biochemical and neuropathological findings of AD in DS.

Residential injury is a leading cause of morbidity and mortality in US children. Rates and types of injury vary by child age but little is known about injury risk based on child cognitive and motor abilities. The objective of this study was to determine whether cognitive or motor development in young children is associated with residential injury.We employed data from Health Outcomes and Measures of the Environment (HOME) Study. Parent report of medically attended injury was obtained at regular intervals from 0 to 42 months. Child development was assessed at 12, 24 and 36 months using Bayley Scales of Infant and Toddler Development, 2nd edition, which generates both mental developmental index (MDI) and a psychomotor developmental index (PDI). Injury risk was modelled using multivariable logistic regression as function of child's MDI or PDI. Effects of MDI and PDI on injury risk were examined separately and jointly, adjusting for important covariates.Children with cognitive delay (MDI77) were at significantly higher risk of injury than children without cognitive delay (OR=3.7, 95% CI 1.4 to 10.5, p=0.012). There was no significant association of PDI with injury. There was, however, significant interaction of MDI and PDI (p=0.02); children with cognitive delay but normal motor development were at significantly higher risk of injury than children with normal cognitive and motor development (OR=9.6, 95% CI 2.6 to 35.8, p=0.001).Children with cognitive delays, especially those with normal motor development, are at elevated risk for residential injuries. Injury prevention efforts should target children with developmental delays.NCT00129324; post-results.

Previous research has revealed similarities in the neuropathology, clinical presentation, and risk factors between persons with Alzheimer’s disease from the general population (GP-AD) and those with Down syndrome (DS-AD). Less is known, however, about the extent of similarities and differences in the cognitive profiles of these two populations. Fifty-one moderate-to-severely demented GP-AD and 59 DS-AD individuals participated in this study which compared the cognitive profiles of these two populations on the Severe Impairment Battery (SIB), controlling for gender as well as level of functional ability using a modified version of the Bristol Activities of Daily Living Scale. Overall, the neuropsychological profiles of the higher-functioning individuals within the DS-AD and advanced GP-AD groups, as represented by mean difference scores on the SIB as a whole and across the nine separate cognitive domains, were very similar to one another after adjusting for gender and functional impairment. To our knowledge, this is the first study to directly compare the cognitive profiles of these two populations on the SIB. Findings suggest that the underlying dementia in GP-AD and DS-AD may have corresponding and parallel effects on cognition.

Utilization of bariatric surgery has changed dramatically over the past two decades. The aim of this study was to update the trends in volume and procedural type of bariatric surgery in the USA. Data were derived from the National Inpatient Sample from 2009 through 2012. We used ICD-9 diagnosis and procedural codes to identify all hospitalizations during which a bariatric procedure was performed for the treatment of severe obesity. The data were reviewed for patient demographics and characteristics, annual number of bariatric operations, and specific procedural types and proportion of laparoscopic cases. The US Census data were used to calculate the population-based annual rate of bariatric surgery per 100,000 adults. Between 2009 and 2012, the number of inpatient bariatric operations ranged between 81,005 and 114,780 cases annually. During this time period, the annual rate of bariatric procedures was highest for 2012 at 47.3 procedures per 100,000 adults. The bariatric surgery approach most commonly performed continues to be laparoscopic, ranging between 93.1 and 97.1 %. In 2012, there was a precipitous reduction in the number of gastric bypass and gastric banding operations and replaced by an increase in the number of sleeve gastrectomy operation. The in-hospital mortality rate remains low, ranging from 0.07 to 0.10 %. In the USA, the annual volume of inpatient bariatric surgery continues to be stable. Utilization of the laparoscopic approach to bariatric surgery remains high, while the in-hospital mortality continues to be low at ≤0.10 % throughout the 4-year period.

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, atherosclerosis and arteriolosclerosis were used as measures of cerebrovascular pathology and compared in post mortem tissue from individuals with DS (n= 32), sporadic AD (n= 80) and controls (n= 37). CAA was observed with significantly higher frequencies in brains of individuals with DS compared to sporadic AD and controls. Atherosclerosis and arteriolosclerosis were rare in the cases with DS. CAA in DS may be a target for future interventional clinical trials.

OBJECTIVE: The primary endpoints of this study were long-term weight loss, morbidity, and changes in comorbidities and quality of life. BACKGROUND: Bariatric surgery is an effective option for the treatment of severe obesity and its related comorbidities. However, few studies have reported on the long-term outcome (>5 yrs) of bariatric surgery. METHODS: Between 2002 and 2007, 250 patients with a body mass index (BMI) of 35 to 60 kg/m(2) were randomly assigned to undergo laparoscopic gastric bypass or laparoscopic gastric banding. After exclusions, 111 patients underwent gastric bypass and 86 patients underwent gastric banding. Factors predictive of improved weight loss were analyzed using multiple logistic regressions. RESULTS: At baseline, the mean age was 43 ± 10 years and the mean BMI was 46.5 ± 5.6 kg/m(2). At 10-year follow-up, the mean total body weight loss for the entire cohort was −37.5 ± 19.4 kg, −42.4 ± 19.6 kg for gastric bypass versus −27.4 ± 14.5 kg for gastric banding. Late reoperation was significantly higher after gastric banding compared with the gastric bypass group (31.4% vs. 8.1%, respectively, P < 0.01). For the entire cohort, improvement or remission of diabetes occurred in 68%; 61% for hypertension; and 57% for dyslipidemia. The long-term mortality for the entire cohort was 1.0% at a mean follow-up of 9.5 ± 0.4 years. Factors predictive of improved weight loss included the type of operation (ie, gastric bypass), female sex, and the absence of diabetes at baseline. At long-term follow-up, quality of life continues to be improved from baseline for both the groups. CONCLUSIONS: Bariatric surgery is an effective treatment for severe obesity with durable 10-year weight loss and improvement in comorbidities and quality of life. Compared with gastric banding, gastric bypass was associated with better long-term weight loss, lower rate of late reoperation, and improved remission of comorbidities.

BackgroundThe management algorithm for appendiceal adenocarcinoma is not well defined. This study sought to determine whether tumor size or depth of invasion better correlates with the presence of lymph node metastases in appendiceal adenocarcinoma, and to compare these rates with colon adenocarcinoma.Study designA retrospective review of the National Cancer Database was performed to identify patients with appendiceal or colonic adenocarcinoma from 2004 to 2013 who underwent surgical resection. Cases were categorized by tumor size and by T stage. Rates of lymph node metastases were examined as a function of size and T stage.ResultsA total of 3,402 appendiceal and 314,864 colonic cases were identified. For appendiceal adenocarcinoma, larger tumor size was associated with higher T stage: Pearson correlation of 0.41 (95% CI 0.408 to 0.414; p < 0.001). Lymph node metastases were present in 19.1%, 27.8%, 39.6%, 39.4%, 42.4% and 39.1% for tumor sizes 1 to 2 cm, >2 to 3 cm, >3 to 4 cm, >4 to 5 cm, and >5 cm, respectively. Lymph node metastases were present in 0%, 11.2%, 12.3%, 35.5%, and 40.0% for in situ, T1, T2, T3, and T4 tumors, respectively. There was no difference in the rates of lymph node metastases between appendiceal and colonic adenocarcinoma for tumor sizes 3 cm and for T2, T3, and T4 tumors (p < 0.01).ConclusionsIn appendiceal adenocarcinoma, the rate of lymph node metastases is substantial, even for small tumors. Tumor size should play no role in the decision of whether to perform a hemicolectomy. Appendectomy alone does not produce an adequate lymph node sample. Right hemicolectomy should be performed for all appendiceal adenocarcinomas.

In recent years there has been considerable effort to understand the interaction of nanomaterials with the skin. In this study we use an in vivo mouse model of allergic contact dermatitis to investigate how nanoparticles (NPs) may alter allergic responses in skin. We investigate a variety of NPs that vary in size, charge and composition. Results show that small (

This study quantifies the dynamics of maternal mood focusing on unpredictability, and to assess if greater unpredictability of prenatal maternal mood predicts child temperament and internalizing symptoms through early adolescence.The association between prenatal mood predictability and child internalizing symptoms were assessed in two longitudinal cohorts (N's = 227 and 180). Maternal mood was assessed repeatedly during pregnancy as early as 15 weeks' gestation. Predictability of maternal mood was calculated by applying Shannon's entropy to the distribution of responses on mood questionnaires. Maternal reports of child negative affectivity (a predictor of later internalizing) were collected at 6, 12, 24 months and 7 years of age. Child self-reports of anxiety symptoms were collected at 10 years and reports of depression symptoms at 13 years.Fetal exposure to more elevated maternal mood entropy predicted higher levels of child negative affectivity at 12 months (r = .36; p01), 24 months (r = .31; p01) and 7 years (r = .32; p01) of age. In addition, children exposed to higher prenatal maternal mood entropy, reported higher levels of anxiety symptoms at 10 years (r = .24; p01) and elevated depressive symptoms at 13 years (r = .29; p.01). These associations persisted after adjusting for maternal pre and postnatal mood valence (e.g. depression levels) and for other relevant demographic characteristics.Our findings provide strong support for the notion that patterns of maternal mood influence the developing brain. More specifically, they suggest that prenatal maternal mood predictability may be a critical predictor of developmental mental health trajectories and should be considered when assessing early life influences on lifespan mental health.

Author(s): Al-Temimi, Mohammed H; Chandrasekaran, Bindupriya; Phelan, Michael J; Pigazzi, Alessio; Mills, Steven D; Stamos, Michael J; Carmichael, Joseph C | Abstract: BackgroundMotor peripheral nerve injury is a rare but serious event after colorectal surgery, and a nationwide study of this complication is lacking.ObjectiveThe purpose of this study was to report the incidence, trends, and risk factors of motor peripheral nerve injury during colorectal surgery.DesignThe National Surgical Quality Improvement Program database was surveyed for motor peripheral nerve injury complicating colorectal procedures. Risk factors for this complication were identified using logistic regression analysis.SettingsThe study used a national database.PatientsPatients undergoing colorectal resection between 2005 and 2013 were included.Main outcome measuresThe incidence, trends, and risk factors for motor peripheral nerve injury complicating colorectal procedures were measured.ResultsWe identified 186,936 colorectal cases, of which 50,470 (27%) were performed laparoscopically. Motor peripheral nerve injury occurred in 122 patients (0.065%). Injury rates declined over the study period, from 0.025% in 2006 to l0.010% in 2013 (p l 0.001). Patients with motor peripheral nerve injury were younger (mean ± SD; 54.02 ± 15.41 y vs 61.56 ± 15.95 y; p l 0.001), more likely to be obese (BMI ≥30; 43% vs 31%; p = 0.003), and more likely to have received radiotherapy (12.3% vs 4.7%; p l 0.001). Nerve injury was also associated with longer operative times (277.16 ± 169.79 min vs 176.69 ± 104.80 min; p l 0.001) and was less likely to be associated with laparoscopy (p = 0.043). Multivariate analysis revealed that increasing operative time was associated with nerve injury (OR = 1.04 (95% CI, 1.03-1.04)), whereas increasing age was associated with a protective effect (OR = 0.80 (95% CI, 0.71-0.90)).LimitationsThis study was limited by its retrospective nature.ConclusionsMotor peripheral nerve injury during colorectal procedures is uncommon (0.065%), and its rate declined significantly over the study period. Prolonged operative time is the strongest predictor of motor peripheral nerve injury during colorectal procedures. Instituting and documenting measures to prevent nerve injury is imperative; however, special attention to this complication is necessary when surgeons contemplate long colorectal procedures.

© 2014, The Society for Surgery of the Alimentary Tract. Results: We sampled 27,860 patients who underwent colorectal resection. Patients with dehydration had higher risk of ARF compared to patients with BUN/Cr 20 as a marker of relative dehydration. Multivariate analysis using logistic regression was performed to quantify the association of BUN/Cr ratio with ARF.

Background: Several studies have shown improved outcomes associated with accredited bariatric centers. The aim of our study was to examine the outcomes of bariatric surgery performed at accredited versus nonaccredited centers using a nationally representative database. Additionally, we aimed to determine if the presence of bariatric surgery accreditation could lead to improved outcomes for morbidly obese patients undergoing other general laparoscopic operations. Methods: Using the Nationwide Inpatient Sample database, for data between 2008 and 2010, clinical data of morbidly obese patients who underwent bariatric surgery, laparoscopic antireflux surgery, cholecystectomy, and colectomy were analyzed according to the hospital’s bariatric accreditation status. Results: A total of 277,068 bariatric operations were performed during the 3-year period, with 88.4% of cases performed at accredited centers. In-hospital mortality was significantly lower at accredited compared to nonaccredited centers (.08% versus .19%, respectively). Multivariate analysis showed that nonaccredited centers had higher risk-adjusted mortality for bariatric procedures compared to accredited centers (odds ratio [OR] 3.1, P o .01). Post hoc analysis showed improved mortality for patients who underwent gastric bypass and sleeve gastrectomy at accredited centers compared to nonaccredited centers (.09% versus .27%, respectively, P o .01). Patients with a high severity of illness who underwent bariatric surgery also had lower mortality rates when the surgery was performed at accredited versus nonaccredited centers (.17% versus .45%, respectively, P o .01). Multivariate analysis showed that morbidly obese patients who underwent laparoscopic cholecystectomy (OR 2.4, P o .05) and antireflux surgery (OR 2.03, P o .01) at nonaccredited centers had higher rates of serious complications. Conclusion: Accreditation in bariatric surgery was associated with more than a 3-fold reduction in risk-adjusted in-hospital mortality. Resources established for bariatric surgery accreditation may have the secondary benefit of improving outcomes for morbidly obese patients undergoing general laparoscopic operations. (Surg Obes Relat Dis 2014;10:767–773.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Background: Patients with rectal prolapse often have significant comorbidities that lead surgeons to select a perineal resection for treatment despite a reported higher recurrence rate over abdominal approaches. There is a lack of data to support this practice in the laparoscopic era. The objective of this study was to evaluate if risk-adjusted morbidity of perineal surgery for rectal prolapse is actually lower than laparoscopic surgery. Design: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database as performed for patients undergoing surgical treatment of rectal prolapse between 2005 and 2011. Outcomes were analyzed according to procedure-type: laparoscopic rectopexy (LR), laparoscopic resection/rectopexy (LRR), open rectopexy (OR), open resection/rectopexy (ORR), and perineal resection (PR). A multivariate logistic regression was used to compare risk-adjusted morbidity and mortality between each procedure. Main outcome measures were 30-day morbidity and mortality. Results: Among 3,254 cases sampled, a laparoscopic approach was used in 22%, an open abdominal approach in 30%, and PR in 48%. Patients undergoing PR were older (76) and had a higher ASA (3) compared to laparoscopic (58, 2) and open abdominal procedures (58, 2). Risk-adjusted mortality could not be assessed due to a low overall incidence of mortality (0.01%). Overall morbidity was 9.3%. ORR was associated with a higher risk-adjusted morbidity compared to PR (OR: 1.89 CI (1.19–2.99), p=0.03). There were no significant differences in risk-adjusted morbidity found between LR and LRR compared to PR (OR 0.44 CI (0.19–1.03), p=0.18; OR 1.55 CI (0.86–2.77), p=0.18). Laparoscopic cases averaged 27min longer than open cases (p&nbsp

OBJECTIVE: The present study examined the effect of child gender and maternal depressive symptoms on routine supervisory practices of mothers longitudinally. METHOD: Self-report supervision practices were obtained at various time points from 3 months through 3 years of age. RESULTS: From 3 to 36 months, the quantity of time mothers reported supervising decreased from 7.1 to 6.3 hours, and the proportion of time spent in an intense style decreased from 63 to 46%, whereas that spent in a peripheral style increased from 14 to 32%. Mothers reported more time supervising girls and a greater proportion of this was in an intense style. Mothers with elevated depressive symptoms reported more time supervising but a lower proportion in an intense style. CONCLUSION: Over the first 36 months of life, routine patterns of supervision change and these vary as a function of maternal depression symptoms and child gender. Implications for child injury risk are discussed. Language: en

Objective: To examine the trends and outcomes of partial esophagectomy with an intrathoracic anastomosis compared with total esophagectomy with a cervical anastomosis. Background: Controversy exists regarding the optimal surgical approach in the management of esophageal cancer. Methods: Using the Nationwide Inpatient Sample database, yearly trends of patients with esophageal cancer who underwent partial and total esophagectomy were analyzed. Multivariate logistic regression analysis was used to analyze serious morbidity and in-hospital mortality between partial and total esophagectomy. In addition, outcomes were analyzed according to hospital volume, with low-volume centers defined as those with fewer than 10 cases per year and high-volume centers as those with 10 or more cases per year. Results: Between 2001 and 2010, 15,190 esophagectomies were performed for cancer. There was an overall increase in the number of esophagectomy procedures performed (1402 to 1975), with a concomitant reduction in the mortality rate (8.3% to 4.2%), particularly for partial esophagectomy. Partial esophagectomy was the predominant operation (76%). Most operations were performed at low-volume centers (62%), with a recent shift of cases to high-volume center. Compared with total esophagectomy, partial esophagectomy was associated with a shorter length of hospital stay (16 ± 6 vs 19 ± 9 days; P < 0.05), a lower in-hospital mortality rate (5.8% vs 8.3%; P < 0.05), and a lower hospital charge ($119,339 vs $138,496; P < 0.05). On multivariate regression analysis, total esophagectomy was associated with higher serious morbidity (odds ratio, 1.39; P < 0.01) and in-hospital mortality (odds ratio, 1.67; P = 0.03). There were no significant differences in risk-adjusted outcomes between low-volume centers and high-volume center. Conclusions: The number of esophagectomies performed for esophageal cancer has increased over the past decade accompanied by an overall reduction in mortality, particularly for the partial esophagectomy approach. The predominant operation in the United States continues to be partial esophagectomy with an intrathoracic anastomosis, which was associated with lower morbidity and in-hospital mortality than total esophagectomy. Hospital volume at a threshold of 10 cases per year was not a predictor of outcome. © 2013 Lippincott Williams & Wilkins.

The necessity of routine endoscopic retrograde cholangiopancreatography (ERCP) after positive intraoperative cholangiogram (IOC) during laparoscopic cholecystectomy is not well defined. We aimed to examine the incidence of positive IOC among patients who undergo IOC during cholecystectomy and the rate of subsequent ERCP stone extraction. The Nationwide Inpatient Sample database was reviewed for all patients undergoing cholecystectomy with IOC from 2002 to 2012. Patients were then analyzed for ERCP and stone extraction. A total of 73,508 patients who underwent cholecystectomy with IOC for a diagnosis of acute cholecystitis and found to have a bile duct stone were identified. Of these patients, 5915 underwent subsequent ERCP. In the patients that underwent subsequent ERCP, 1478 had a documented stone extraction during ERCP. The rate of stone extraction in the ERCP subset is 25 per cent, which is 2 per cent of all patients who had a positive IOC. The rate of stone extraction after positive IOC is low. Positive IOC may not warrant a routine postoperative ERCP. Our results suggest that clinical monitoring of patients with positive IOC is reasonable, as the majority of patients with a positive IOC ultimately have no stone extraction.

Disparities in access to health care between white and minority patients are well described. We aimed to analyze the trends and outcomes of cholecystectomy based on racial classification. The Nationwide Inpatient Sample database was reviewed for all patients undergoing cholecystectomy from 2009 to 2012. Patients were stratified as white or non-white. A total of 243,536 patients were analyzed: 159,901 white and 83,635 non-white. Non-white patients had significantly higher proportions of Medicaid (25% vs 9.3%), self-pay (14% vs 7.1%), and no-charge (1.8% vs 0.64%). Non-white patients had significantly higher rates of emergent admission (84% vs 78%) compared with the white patients. Multivariate analysis revealed that non-whites had a significantly longer length of stay [mean difference of 0.14 days, 95% confidence interval (CI) 0.08-0.20] and higher total hospital charges (mean difference of $6748.00, 95% CI 5994.19-7501.81) than whites, despite a lower morbidity (odds ratio 0.94, 95% CI 0.90-0.98). Use of laparoscopy and mortality were not different. These differences persisted on subgroup analysis by insurance type. These findings suggest a gap in access to and outcomes of cholecystectomy in the minority population nationwide.

peer-reviewed Despite extensive efforts, cancer therapies directed at the Protein Kinase C (PKC) family of serine/threonine kinases have failed in clinical trials. These therapies have been directed at inhibiting PKC and have, in some cases, worsened disease outcome. Here we examine colon cancer patients and show not only that PKC Beta II is a tumour suppressor, but patients with low levels of this isozyme have significantly decreased disease free survival. Specifically, analysis of gene expression levels of all PKC genes in matched normal and cancer tissue samples from colon cancer patients revealed a striking down-regulation of the gene coding PKC Beta in the cancer tissue (n = 21). Tissue microarray analysis revealed a dramatic down-regulation of PKC Beta II protein levels in both the epithelial and stromal diseased tissue (n = 166). Of clinical significance, low levels of the protein in the normal tissue of patients is associated with a low (10%) 10 year survival compared with a much higher (60%) survival in patients with relatively high levels of the protein. Consistent with PKC Beta II levels protecting against colon cancer, overexpression of PKC Beta II in colon cancer cell lines reveals that PKC Beta II reverses transformation in cell based assays. Further to this, activation of PKC Beta II results in a dramatic downregulation of IGF-I-induced AKT, indicating a role for PKCs in regulating IGF-1 mediated cell survival. Thus, PKC Beta II is a tumour suppressor in colon cancer and low levels serve as a predictor for poor survival outcome. PUBLISHED peer-reviewed

There is no published data regarding the relationship between hospital volume and outcomes in patients undergoing laparoscopic diaphragmatic hernia repair. We hypothesize that hospitals performing high case volume have improved outcomes compared to low-volume hospitals.We reviewed the National Inpatient Sample (NIS) database between 2008 and 2012 for adults with the diagnosis of diaphragmatic hernia who underwent elective laparoscopic repair of diaphragmatic Hernia and/or Nissen fundoplication. Pediatric, emergent, and open cases were excluded. Main outcome measures included logistic regression analysis of factors predictive of in-hospital mortality and outcomes according to annual hospital case volume.A total of 31,228 laparoscopic diaphragmatic hernia operations were analyzed. The overall in-hospital mortality was 0.14%. Risk factors for higher in-hospital mortality included renal failure (AOR: 6.26; 95% CI: 2.48-15.78; p 60 years (AOR: 5.06; 95% CI: 2.38-10.76; p

Objective Up to 90% of adolescents with attention deficit hyperactivity disorder (ADHD) remain functionally impaired, yet less than half continue to take medication. The objective of this study was to gain a detailed understanding of how adolescents with ADHD contribute to medication treatment decisions. Methods Forty-four adolescents with ADHD aged 13 to 18 years old participated in 1 of 7 focus groups. An experienced facilitator used a semi-structured focus group guide to prompt discussion which was audio-recorded and transcribed verbatim. We coded transcripts using an inductive approach. Thematic saturation was reached after the seventh focus group. Results Adolescents assumed increased responsibility for managing medication as they matured and developed insight into the functional impact of ADHD and medication on their lives. Insights were often formed by contrasting time spent on and off medication. ADHD impacted functioning in the following domains: academics, social interactions and relationships, creativity, and driving skills. Select domains were relevant for some adolescents but not others. Adolescents described different roles that they played in managing medication as well as strategies they used to exert autonomy over medication use. Side effects were common and contributed to negative feelings toward medication. Some adolescents had begun to use medication selectively. Many expressed uncertainty about future use of medication. Conclusions Adolescents assume an increasing role in managing medication for ADHD. Well-structured and coordinated trials stopping medication and measuring outcomes relevant to adolescents, parents, teachers, doctors, and/or other stakeholders may help ensure a developmentally appropriate transition from family to self-management of ADHD.

Across 366 California hospitals, we identified hospital-level characteristics predicting increased hospital-associated Clostridium difficile infection (HA-CDI) rates including more licensed beds, teaching and long-term acute care (LTAC) hospitals, and polymerase chain reaction testing. Adjustment for these characteristics impacted rankings in 24% of teaching hospitals, 13% of community hospitals, and 11% of LTAC hospitals.Infect Control Hosp Epidemiol 2015;00(0): 1–3

Background: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. Methods: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. Results: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001 ) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). Conclusions: This study confirms the higher bleeding risk associated with HD/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. Summary: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A secondary finding was that INR variability was significantly higher in HD patients than non-HD patients on warfarin.

The objectives of this study are to assess: (a) the prevalence of vitamin D deficiency among new patients attending rheumatology outpatient departments, (b) the age profile of these low vitamin D patients and (c) whether any diagnostic category had a particularly high number of vitamin D-deficient patients. All new patients seen consecutively in general rheumatology clinics between January to June 2007 inclusive were eligible to partake in this study, and 231 out of 264 consented to do so. Parathyroid hormone, 25-hydroxyvitamin D, creatinine, calcium, phosphate, albumin and alkaline phosphatase levels were measured. We defined vitamin D deficiency as ≤53 nmol/l and severe deficiency as ≤25 nmol/l. Overall, 70% of 231 patients had vitamin D deficiency, and 26% had severe deficiency. Sixty-five percent of patients aged ≥65 and 78% of patients aged ≤30 years had low vitamin D levels. Vitamin D deficiency in each diagnostic category was as follows: (a) inflammatory joint diseases/connective tissue diseases (IJD/CTD), 69%; (b) soft tissue rheumatism, 77%; (c) osteoarthritis, 62%; (d) non-specific musculoskeletal back pain, 75% and (e) osteoporosis, 71%. Seasonal variation of vitamin D levels was noted in all diagnostic groups apart from IJD/CTD group, where the degree of vitamin D deficiency persisted from late winter to peak summer. Very high prevalence of vitamin D deficiency was noted in all diagnostic categories (p = 0.006), and it was independent of age (p = 0.297). The results suggest vitamin D deficiency as a possible modifiable risk factor in different rheumatologic conditions, and its role in IJD/CTD warrants further attention.

Steroid therapy is associated with significant morbidity in renal transplant recipients. However, there is concern that steroid withdrawal will adversely affect outcome. We report on 241 renal transplant recipients on different doses of corticosteroids at 3 months (zero, ≤5 mg/day, >5 mg/day). Parameters analysed included blood pressure, lipid profile, weight change, new onset diabetes after transplantation (NODAT), allograft survival and acute rejection. Elimination of corticosteroids had no impact on allograft survival at 1 year. There were no cases of NODAT in the steroid withdrawal group compared with over 7% in each of the steroid groups. There were no significant improvements in weight gain, blood pressure control or total cholesterol with withdrawal of steroids before 3 months. In renal transplant patients treated with tacrolimus and mycophenolate, early withdrawal of steroids does not appear to adversely affect allograft outcome at 1 year. It may result in less NODAT.

Encapsulating peritoneal sclerosis (EPS) is arguably the most serious complication of chronic peritoneal dialysis (PD) therapy with extremely high mortality rates. We aimed to establish the rates of EPS and factors associated with its development in a single center.We retrospectively reviewed the records of all our PD patients from 1 January 1989 until 31 December 2008. All suspected cases were confirmed at laparotomy. Multifactorial models adjusted for potentially confounding variables such as age and sex.Eleven cases of EPS were identified giving a prevalence rate of 1.98%. Median duration on PD was substantially longer in affected versus unaffected patients (42.5 months versus 13.8 months; p = 0.0002). EPS patients had experienced a mean of 3.54 previous cases of peritonitis (1 infection per year versus 0.71 per year in unaffected patients; p = 0.075). Six patients died (54.5%) due to intra-abdominal sepsis including all five who presented with small bowel obstruction. Three patients had an omentectomy and adhesiolysis performed with a successful outcome.Our study reinforces the link between duration on PD and EPS. While mortality was high in our cohort, emerging surgical techniques demonstrate a favorable outcome that can be achieved even in severely affected cases.

We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

To identify cardiovascular and other comorbidities in a general rheumatology cohort.Interviews/retrospective chart audits were conducted on 1,000 patients attending rheumatology outpatient clinics of a university teaching hospital. Comorbidities were classified using the Charlson comorbidity index (Ambrose et al. in Ir J Med Sci 178(1):53-55, 2009).Mean age 58 +/- 15.3 years, mean BMI 26. Of the patients, 400 (40%) were diagnosed with dyslipidemia and hypertension (p = 0.002), 160 (16%) with obesity and 80 (8%) with hypothyroidism. Overall 160 (16%) patients were diagnosed with coronary heart disease (CHD). Of these, 120 (75%) had RA (p = 0.001), 100 (63%) were male, mean age 60 +/- 15.8 years, 120 (75%) had dyslipidemia and BMI30 (p = 0.002), 112 (70%) were smokers (p = 0.002), 40 (25%) were diagnosed with diabetes mellitus and 20 (12%) with hypothyroidism.The increased prevalence of these comorbidities may serve as a reminder to the rheumatologists that many of their patients will have coexistent disease of which they need to be aware to properly plan their management.

It has been suggested that the left kidney is easier to transplant than the right kidney because of the longer length of the left renal vein, facilitating the formation of the venous anastomosis. There are conflicting reports of differing renal allograft outcomes based on the side of donor kidney transplanted (left or right).We sought to determine the effect of side of donor kidney on early and late allograft outcome in our renal transplant population. We performed a retrospective analysis of transplanted left-right deceased donor kidney pairs in Ireland between January 1, 1998 and December 31, 2008. We used a time to death-censored graft failure approach for long-term allograft survival and also examined serum creatinine at different time points post-transplantation. All outcomes were included from day of transplant onwards. A total of 646 transplants were performed from 323 donors. The incidence of delayed graft function was 16.1% in both groups and there was no significant difference in acute rejection episodes or serum creatinine from 1 month to 8 years post-transplantation.There were 47 death-censored allograft failures in the left-sided group compared to 57 in the right-sided group (P = 0.24). These observations show no difference in renal transplant outcome between the recipients of left- and right-sided deceased donor kidneys.

Multiple studies examining the impact of resident involvement on patient outcomes in general surgical operations have shown an associated increase in morbidity and operative time. However, these studies included basic and advanced laparoscopic and open operations. The aim of this study was to examine the impact of resident involvement on outcomes specifically in patients who underwent complex minimally invasive gastrointestinal operations.The American College of Surgeons NSQIP database was reviewed for patients who underwent laparoscopic colectomy and laparoscopic paraesophageal hernia and anti-reflux procedures between 2002 and 2010. Data were analyzed based on operations performed with a resident involved compared with those performed by an attending surgeon without resident involvement. Primary end points included risk-adjusted 30-day mortality, 30-day reoperation, and 30-day serious morbidity. Secondary end points were operative time, hospital length of stay, and 30-day overall morbidity.A total of 31,736 cases were analyzed; 63.3% of cases had a resident involved in the operation and 36.7% were performed by an attending without resident involvement. Operative time was significantly longer in cases performed with a resident (162 vs 138 minutes in attending-only cases; p0.01), however, there were no significant differences between groups with regard to hospital length of stay (4.5 vs 4.5 days, respectively). Compared with cases without resident involvement, risk-adjusted outcomes for cases with resident involvement showed no significant differences in 30-day serious morbidity (odds ratio = 1.03; 95% CI, 0.94-1.14; p = 1.0), 30-day mortality (odds ratio = 0.83; 95% CI, 0.60-1.15; p = 1.0), or 30-day reoperation (odds ratio = 0.93; 95% CI, 0.81-1.06; p = 1.0).Resident involvement in complex laparoscopic gastrointestinal procedures is associated with an increase in operative time with no impact on postoperative outcomes.

Background: Few data exist on the effect of maternal depression on child injury outcomes and mediators of this relationship. Objective: To examine the relationship between mothers’ depressive symptoms and medically attended injuries in their children and the potential mediating role of child behavior. Design/Methods: A cohort of mother–child dyads from the National Longitudinal Study of Youth followed from 1992 to1994. The primary exposure variable was maternal depressive symptoms as measured by the Center for Epidemiologic Studies Depression Scale in 1992. Child behavior was assessed by the Behavior Problems Index externalizing subscale. Logistic regression was used to examine the relationship between depressive symptoms, child behavior, and injury reported in the prior year in 1994. Results: 94 medically attended injuries were reported in the 1106 children (8.5%); two-thirds were sustained in the home environment. Maternal depressive symptoms significantly increased the risk of child injury; injury risk increased 4% for every 1-point increase in depressive symptoms (adjusted OR 1.04, 95% CI 1.01 to 1.08, p = 0.02). Increasing maternal depressive symptoms also increased the risk of externalizing behavior problems (adjusted OR 1.06, 95% CI 1.03 to 1.09), but externalizing behavior problems did not significantly mediate the relationship between maternal symptoms and child injury. Conclusions: Increasing depressive symptoms in mothers was associated with an increased risk of child injury. Child behavior did not significantly mediate the association between maternal depressive symptoms and child injury in this cohort. Greater recognition, referral, and treatment of depressive symptoms in mothers may have effects on child behavior and injury risk.

Author(s): Moghadamyeghaneh, Zhobin; Phelan, Michael; Smith, Brian R; Stamos, Michael J | Abstract: BackgroundThere are limited available data comparing open, laparoscopic, and robotic approaches for rectal cancer surgery.ObjectiveWe sought to investigate outcomes of different surgical approaches to abdominoperineal resection in patients with rectal cancer.DesignThe nationwide inpatient sample database was used to examine the clinical data of patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012 in the United States. Multivariate regression analysis was performed to compare outcomes of different surgical approaches.SettingsA retrospective review according to the national inpatient sample database was designed.PatientsWe included patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012.Main outcome measuresOutcomes of different surgical approaches to abdominoperineal resection were investigated.ResultsWe sampled 18,359 patients with rectal cancer who underwent elective abdominoperineal resections. Of these, 69.5% had open surgery, 25.8% had laparoscopic surgery, and 4.7% had robotic surgery. The rate of robotic procedures increased g4-fold, from 2.1% to 8.1%, from 2009 to 2012. The conversion rate in robotic surgery was significantly lower compared with laparoscopic surgery (5.7% vs 13.4%; p l 0.01). After risk adjustment, patients who underwent laparoscopic and robotic approaches had lower morbidity risks compared with those who underwent the open approach (adjusted OR = 0.77 (95% CI, 0.65-0.92), 0.57 (95% CI, 0.40-0.80); p l 0. 01). There were no significant differences in the morbidity rate of patients who underwent laparoscopic or robotic approaches (adjusted OR = 0.79 (95% CI, 0.55-1.14); p = 0.21). However, patients who underwent the robotic approach had significantly higher total hospital charges compared with those who underwent the laparoscopic approach (mean difference, $24,890; p l 0.01).LimitationsWe could not adjust the results with some important factors, such as the tumor stage and BMI.ConclusionsThe use of robotic and laparoscopic approaches to abdominoperineal resection have increased between 2009 and 2012. Both minimally invasive approaches decrease morbidity rates of patients undergoing abdominoperineal resection. The robotic approach has a significantly lower conversion rate compared with the laparoscopic approach. However, it had significantly higher total hospital charges compared with the laparoscopic approach.

Male obesity rates are now estimated to be equal to female obesity rates. Despite this, men constitute a minority of patients undergoing bariatric surgery. The aim of this study was to examine the national trends and outcomes of bariatric surgery in male patients compared with female patients.The Nationwide Inpatient Sample database was reviewed for obese patients undergoing bariatric surgery between 2002 and 2011. Outcomes were analyzed according to sex. Main outcomes measures were patient demographics, length of stay, risk-adjusted inpatient morbidity and mortality, and hospital charge.During the 10-year period, 810,999 patients underwent bariatric surgery; 19.3% were male and 80.7% were female. The percentage of male patients increased from 15.4% in 2002 to 21.7% in 2011. Mean age was significantly older for males (46 ± 11 years vs 43 ± 11 years; p0.01, respectively). Male patients had a higher proportion of moderate, major, and extreme severity of illness classifications and higher rates of comorbid conditions. Serious morbidity was significantly higher in male patients compared with female patients (7.58% vs 5.42%; p0.01). Mean hospital length of stay was longer for male patients (2.75 vs 2.61 days; p0.01) with a higher mean hospital charge ($38,682 vs $34,294; p0.01). Compared with the female group, the male group had higher risk-adjusted in-hospital mortality (odds ratio = 2.16; 95% CI, 1.62-2.88; p0.01) and serious morbidity (odds ratio = 1.23; 95% CI, 1.17-1.29; p0.01).The number of male patients undergoing bariatric surgery in the past decade continues to be a small fraction compared with the number of female patients. Men undergoing bariatric surgery tend to have higher severity of illness, with higher risk-adjusted serious morbidity and mortality rates. Additional studies are necessary to examine barriers in obtaining treatment for obese men.

Adhesions account for 74 per cent of admissions for small bowel obstruction (SBO). There is a lack of data regarding the usage and outcomes of laparoscopy (LS) for SBO. A retrospective review of urgent admissions for SBO using the Nationwide Inpatient Sample 2001 to 2011 was conducted. Among the estimated 3,948,987 SBO admissions, 36.7 per cent underwent operative management and LS was performed in 26.5 per cent with a 22.5 per cent conversion rate. Admissions increased by 3.1 per cent annually, whereas nonoperative management increased by 3.8 per cent annually. Operative management increased by 1.8 per cent annually, whereas LS increased by 8.9 per cent annually and open surgery decreased by 0.6 per cent annually. LS small bowel resection increased by a mean of 25 per cent annually. LS was associated with a 24.4 per cent in-hospital morbidity with intra-abdominal abscess/enteric fistulas (8.3%) and ileus (8.9%) as the most common complications. In-hospital mortality was 0.9 per cent with length of stay of 13 ± 9 days and a hospital charge of $80,080 ± 6,634. The majority of patients were operated on hospital day (HD) 1 (43.0%). Patients who underwent LS on HD7 had a higher risk-adjusted mortality compared with earlier HD (odds ratio = 2.63; 95% confidence interval: 2.40-2.89; P0.01). There has been an increase in admissions for SBO and an increase in LS over the past 11 years. There seems to be an increase in mortality and morbidity with a later HD operation.