High level of complexity and global diversity of the 3q29 locus revealed by optical mapping and long-read sequencing.

BACKGROUND: High sequence identity between segmental duplications (SDs) can facilitate copy number variants (CNVs) via non-allelic homologous recombination (NAHR). These CNVs are one of the fundamental causes of genomic disorders such as the 3q29 deletion syndrome (del3q29S). There are 21 protein-coding genes lost or gained as a result of such recurrent 1.6-Mbp deletions or duplications, respectively, in the 3q29 locus. While NAHR plays a role in CNV occurrence, the factors that increase the risk of NAHR at this particular locus are not well understood. METHODS: We employed an optical genome mapping technique to characterize the 3q29 locus in 161 unaffected individuals, 16 probands with del3q29S and their parents, and 2 probands with the 3q29 duplication syndrome (dup3q29S). Long-read sequencing-based haplotype resolved de novo assemblies from 44 unaffected individuals, and 1 trio was used for orthogonal validation of haplotypes and deletion breakpoints. RESULTS: In total, we discovered 34 haplotypes, of which 19 were novel haplotypes. Among these 19 novel haplotypes, 18 were detected in unaffected individuals, while 1 novel haplotype was detected on the parent-of-origin chromosome of a proband with the del3q29S. Phased assemblies from 44 unaffected individuals enabled the orthogonal validation of 20 haplotypes. In 89% (16/18) of the probands, breakpoints were confined to paralogous copies of a 20-kbp segment within the 3q29 SDs. In one del3q29S proband, the breakpoint was confined to a 374-bp region using long-read sequencing. Furthermore, we categorized del3q29S cases into three classes and dup3q29S cases into two classes based on breakpoints. Finally, we found no evidence of inversions in parent-of-origin chromosomes. CONCLUSIONS: We have generated the most comprehensive haplotype map for the 3q29 locus using unaffected individuals, probands with del3q29S or dup3q29S, and available parents, and also determined the deletion breakpoint to be within a 374-bp region in one proband with del3q29S. These results should provide a better understanding of the underlying genetic architecture that contributes to the etiology of del3q29S and dup3q29S.

Whole-exome sequencing and adrenocorticotropic hormone therapy in individuals with infantile spasms.

AIM: To identify additional genes associated with infantile spasms using a cohort with defined infantile spasms. METHOD: Whole-exome sequencing (WES) was performed on 21 consented individuals with infantile spasms and their unaffected parents (a trio-based study). Clinical history and imaging were reviewed. Potentially deleterious exonic variants were identified and segregated. To refine potential candidates, variants were further prioritized on the basis of evidence for relevance to disease phenotype or known associations with infantile spasms, epilepsy, or neurological disease. RESULTS: Likely pathogenic de novo variants were identified in NR2F1, GNB1, NEUROD2, GABRA2, and NDUFAF5. Suggestive dominant and recessive candidate variants were identified in PEMT, DYNC1I1, ASXL1, RALGAPB, and STRADA; further confirmation is required to support their relevance to disease etiology. INTERPRETATION: This study supports the utility of WES in uncovering the genetic etiology in undiagnosed individuals with infantile spasms with an overall yield of five out of 21. High-priority candidates were identified in an additional five individuals. WES provides additional support for previously described disease-associated genes and expands their already broad mutational and phenotypic spectrum.

Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans.

Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r2 ≥ 0.8), indicating that associations with our internally called CNVs were not captured by previous SNP-based GWASs. Here, we present a GWAS and gene set analysis of the relationship between normal facial variation and CNVs in a sample of Bantu African children. We report the top five regions, which had p values ≤ 9.35 × 10-6 and find nominal evidence of independent CNV association (p < 0.05) in three regions previously identified in SNP-based GWASs. The CNV region with strongest association (p = 1.16 × 10-6, 55 losses and seven gains) contains NFATC1, which has been linked to facial morphogenesis and Cherubism, a syndrome involving abnormal lower facial development. Genomic loss in the region is associated with smaller average lower facial depth. Importantly, new loci identified here were not identified in a SNP-based GWAS, suggesting that CNVs are likely involved in determining facial shape variation. Given the plethora of SNP-based GWASs, calling CNVs from existing data may be a relatively inexpensive way to aid in the study of complex traits.

22q11.2 Low Copy Repeats Expanded in the Human Lineage.

Segmental duplications or low copy repeats (LCRs) constitute duplicated regions interspersed in the human genome, currently neglected in standard analyses due to their extreme complexity. Recent functional studies have indicated the potential of genes within LCRs in synaptogenesis, neuronal migration, and neocortical expansion in the human lineage. One of the regions with the highest proportion of duplicated sequence is the 22q11.2 locus, carrying eight LCRs (LCR22-A until LCR22-H), and rearrangements between them cause the 22q11.2 deletion syndrome. The LCR22-A block was recently reported to be hypervariable in the human population. It remains unknown whether this variability also exists in non-human primates, since research is strongly hampered by the presence of sequence gaps in the human and non-human primate reference genomes. To chart the LCR22 haplotypes and the associated inter- and intra-species variability, we de novo assembled the region in non-human primates by a combination of optical mapping techniques. A minimal and likely ancient haplotype is present in the chimpanzee, bonobo, and rhesus monkey without intra-species variation. In addition, the optical maps identified assembly errors and closed gaps in the orthologous chromosome 22 reference sequences. These findings indicate the LCR22 expansion to be unique to the human population, which might indicate involvement of the region in human evolution and adaptation. Those maps will enable LCR22-specific functional studies and investigate potential associations with the phenotypic variability in the 22q11.2 deletion syndrome.

Genome-wide copy number variations in a large cohort of bantu African children.

BACKGROUND: Copy number variations (CNVs) account for a substantial proportion of inter-individual genomic variation. However, a majority of genomic variation studies have focused on single-nucleotide variations (SNVs), with limited genome-wide analysis of CNVs in large cohorts, especially in populations that are under-represented in genetic studies including people of African descent. METHODS: We carried out a genome-wide copy number analysis in > 3400 healthy Bantu Africans from Tanzania. Signal intensity data from high density (> 2.5 million probes) genotyping arrays were used for CNV calling with three algorithms including PennCNV, DNAcopy and VanillaICE. Stringent quality metrics and filtering criteria were applied to obtain high confidence CNVs. RESULTS: We identified over 400,000 CNVs larger than 1 kilobase (kb), for an average of 120 CNVs (SE = 2.57) per individual. We detected 866 large CNVs (≥ 300 kb), some of which overlapped genomic regions previously associated with multiple congenital anomaly syndromes, including Prader-Willi/Angelman syndrome (Type1) and 22q11.2 deletion syndrome. Furthermore, several of the common CNVs seen in our cohort (≥ 5%) overlap genes previously associated with developmental disorders. CONCLUSIONS: These findings may help refine the phenotypic outcomes and penetrance of variations affecting genes and genomic regions previously implicated in diseases. Our study provides one of the largest datasets of CNVs from individuals of African ancestry, enabling improved clinical evaluation and disease association of CNVs observed in research and clinical studies in African populations.

Genomic regions associated with microdeletion/microduplication syndromes exhibit extreme diversity of structural variation.

Segmental duplications (SDs) are a class of long, repetitive DNA elements whose paralogs share a high level of sequence similarity with each other. SDs mediate chromosomal rearrangements that lead to structural variation in the general population as well as genomic disorders associated with multiple congenital anomalies, including the 7q11.23 (Williams-Beuren Syndrome, WBS), 15q13.3, and 16p12.2 microdeletion syndromes. Population-level characterization of SDs has generally been lacking because most techniques used for analyzing these complex regions are both labor and cost intensive. In this study, we have used a high-throughput technique to genotype complex structural variation with a single molecule, long-range optical mapping approach. We characterized SDs and identified novel structural variants (SVs) at 7q11.23, 15q13.3, and 16p12.2 using optical mapping data from 154 phenotypically normal individuals from 26 populations comprising five super-populations. We detected several novel SVs for each locus, some of which had significantly different prevalence between populations. Additionally, we localized the microdeletion breakpoints to specific paralogous duplicons located within complex SDs in two patients with WBS, one patient with 15q13.3, and one patient with 16p12.2 microdeletion syndromes. The population-level data presented here highlights the extreme diversity of large and complex SVs within SD-containing regions. The approach we outline will greatly facilitate the investigation of the role of inter-SD structural variation as a driver of chromosomal rearrangements and genomic disorders.

Assessing climate-induced agricultural vulnerable coastal communities of Bangladesh using machine learning techniques.

The agricultural arena in the coastal regions of South-East Asian countries is experiencing the mounting pressures of the adverse effects of climate change. Controlling and predicting climatic factors are difficult and require expensive solutions. The study focuses on identifying issues other than climatic factors using the Livelihood Vulnerability Index (LVI) to measure agricultural vulnerability. Factors such as monthly savings of the farmers, income opportunities, damage to cultivable lands, and water availability had significant impacts on increasing community vulnerability with regards to agricultural practice. The study also identified the need for assessing vulnerability after certain intervals, specifically owing to the dynamic nature of the coastal region where the factors were found to vary among the different study areas. The development of a climate-resilient livelihood vulnerability assessment tool to detect the most significant factors to assess agricultural vulnerability was done using machine learning (ML) techniques. The ML techniques identified nine significant factors out of 21 based on the minimum level of standard deviation (0.03). A practical application of the outcome of the study was the development of a mobile application. Custom REST APIs (application programming interface) were developed on the backend to seamlessly sync the app to a server, thus ensuring the acquisition of future data without much effort and resources. The paper provides a methodology for a unique vulnerability assessment technique using a mobile application, which can be used for the planning and management of resources by different stakeholders in a sustainable way.

Abnormal expression of GABAA receptor subunits and hypomotility upon loss of gabra1 in zebrafish.

We used whole-exome sequencing (WES) to determine the genetic etiology of a patient with a multi-system disorder characterized by a seizure phenotype. WES identified a heterozygous de novo missense mutation in the GABRA1 gene (c.875C>T). GABRA1 encodes the alpha subunit of the gamma-aminobutyric acid receptor A (GABAAR). The GABAAR is a ligand gated ion channel that mediates the fast inhibitory signals of the nervous system, and mutations in the subunits that compose the GABAAR have been previously associated with human disease. To understand the mechanisms by which GABRA1 regulates brain development, we developed a zebrafish model of gabra1 deficiency. gabra1 expression is restricted to the nervous system and behavioral analysis of morpholino injected larvae suggests that the knockdown of gabra1 results in hypoactivity and defects in the expression of other subunits of the GABAAR. Expression of the human GABRA1 protein in morphants partially restored the hypomotility phenotype. In contrast, the expression of the c.875C>T variant did not restore these behavioral deficits. Collectively, these results represent a functional approach to understand the mechanisms by which loss-of-function alleles cause disease.

Comparing febrile children presenting on and off antibiotics to the emergency department: a retrospective cohort study.

BACKGROUND: It is not yet known how antibiotics may affect Serious Bacterial Infections (SBI). Our aim is to describe the presentation, management, and serious bacterial infections (SBI) of febrile children on or off antibiotics. METHODS: Retrospective, cohort study of febrile Emergency Department patients, 0-36 months of age, at a single institution, between 2009and 2012. RESULTS: Seven hundred fifty-three patients were included: 584 in the No-Antibiotics group and 169 (22%) in the Antibiotics group. Age and abnormal lung sounds were predictors for being on antibiotics (OR 2.00 [95% CI 1.23-3.25] and OR 1.04 [95% CI 1.02-1.06] respectively) while female gender, and lower temperatures were negative predictors (OR 0.68 [95%0.47-0.98] and OR 0.47 [95% CI 0.32-0.67] respectively). Antibiotics were prescribed by a physician 89% of the time; the most common one being Amoxicillin/Clavulanic Acid (39%). The antibiotic group got more blood tests (57% vs 45%) and Chest X-Rays (37% vs 25%). Overall, the percent of SBIs (and pneumonias) was statistically the same in both groups (6.5% in the No-antibiotic group VS 3.6%). CONCLUSIONS: Children presenting on antibiotics and off antibiotics were significantly different in their presentation and management, although the overall percentages of SBI were similar in each group. Further investigations into this subgroup of febrile children are needed.

Reviewing the evidence on vasomotor symptoms: the role of traditional and non-traditional factors.

This narrative review aims to synthesize evidence on factors that may influence the severity, occurrence, and incidence of vasomotor symptoms (VMS) that encompass hot flashes and/or night sweats. A comprehensive literature search was conducted electronically using Web of Science, Ovid MEDLINE, PubMed, and Google Scholar to retrieve all English language studies on predictors of VMS from 2000 to 2018. Studies evaluating treatment options for VMS, studies of women with comorbidities such as breast cancer or osteoporosis, studies on VMS outcomes, and studies on quality of life among women with VMS were excluded. After screening, 88 articles were reviewed. Findings showed that different factors such as biological, demographic, behavioral, social, and non-traditional were associated with VMS. The most consistent risk factors of VMS were: being in later menopausal stages, smoking, lower socioeconomic status, higher follicle stimulating hormone levels, ethnicity, and higher body mass index. Most studies were either cross-sectional or observational in design, and were conducted in western countries. A more nuanced understanding of the factors contributing to VMS can assist clinicians in screening women for optimal VMS counseling and treatment. This review found that further large-scale studies set in developing countries that examine VMS factors are warranted.

Drain or No Drain Following Pancreaticoduodenectomy: The Unsolved Dilemma.

BACKGROUND AND AIMS: There is no consensus regarding the routine placement of intra-abdominal drains after pancreaticoduodenectomy. We aim to determine the effects of intraperitoneal drain placement during pancreaticoduodenectomy on 30-day postoperative morbidity and mortality. METHODS: Patients who underwent pancreaticoduodenectomy for pancreatic tumors were identified from the 2014-2015 American College of Surgeons-National Surgical Quality Improvement Program Database. Univariate and multivariate analyses adjusting for known prognostic variables were performed. A subgroup analysis was performed based on the risk for development of postoperative pancreatic leak determined by the pancreatic duct caliber, parenchymal texture, and body mass index. RESULTS: A total of 6858 patients with pancreatic tumors who underwent pancreaticoduodenectomy were identified in the 2014-2015 American College of Surgeons-National Surgical Quality Improvement Program Database dataset. In all, 87.4% of patients had intraperitoneal drains placed. A 30-day mortality rate was higher in the no-drain group (2.9% vs. 1.7%, P = 0.003). Patients in the drain group had a higher incidence of overall morbidity (49.5% vs. 41.2%, P = 0.0008), delayed gastric emptying (18.1% vs. 13.7%, P = 0.004), pancreatic fistulae (19.4% vs. 9.9%, P ⩽ 0.0001), and prolonged length of hospital stay over 10 days (43.7% vs. 34.9%, P < 0.0001). Subgroup analysis based on risk categories revealed a higher 30-day mortality rate in the no-drain group among patients with high-risk features (3.1% vs. 1.6%, P = 0.02). Delayed gastric emptying and pancreatic fistula development remained significantly higher in the drain group only in the high-risk category. Prolonged length of hospital stay and composite morbidity remained higher in the drain group regardless of the risk category. CONCLUSION: To our knowledge, this is the largest study to date that aims at clarifying the pros and cons of the intraperitoneal drain placement during pancreaticoduodenectomy for pancreatic tumors. We showed a higher 30-day mortality rate if drain insertion was omitted during pancreaticoduodenectomy in patients with softer pancreatic textures, smaller pancreatic duct caliber, and body mass index over 25. Postoperative 30-day morbidity rate was higher if a drain was inserted regardless of the risk category. Further randomized controlled trials with prospective evaluation of stratification factors for fistula risk are needed to establish a clear recommendation.

Crohn's disease: A retrospective analysis between computed tomography enterography, colonoscopy, and histopathology.

INTRODUCTION: To investigate the spectrum of computed tomography enterography (CTE) findings of active Crohn's disease (CD) in comparison to endoscopic, histopathologic and inflammatory markers. METHODS: Hospital records of 197 patients with known or suspected CD who underwent CTE over a period of 5 years were reviewed. Eighty-nine patients fulfilled the inclusion criteria. Three-point severity scores for endoscopy, pathology, and haematologic inflammatory markers were recorded. The findings on CTE were identified by three readers and correlated with endoscopic, pathologic, and haematologic severity scores. Statistical analysis was carried out employing a Pearson Chi square test and Fisher exact test. Receiver operating characteristic (ROC), visual grading characteristic (VGC) and Cohens' kappa analyses were performed. RESULTS: The CTE findings which were significantly correlated with the severity of active disease on endoscopy include bowel wall thickening, mucosal hyperenhancement, bilaminar stratified wall enhancement, transmural wall enhancement, and mesenteric fluid adjacent to diseased bowel (p < 0.05). Only bowel wall thickening and bilaminar stratified wall enhancement correlated with the pathological severity of active CD. ROC and VGC analysis demonstrated significantly higher areas under the curve (p < 0.0001) together with excellent inter-reader agreement (k = 0.86). CONCLUSION: CTE is a reliable tool for evaluating the severity of active disease and helps in the clinical decision pathway.

The 22q11 low copy repeats are characterized by unprecedented size and structural variability.

Low copy repeats (LCRs) are recognized as a significant source of genomic instability, driving genome variability and evolution. The Chromosome 22 LCRs (LCR22s) mediate nonallelic homologous recombination (NAHR) leading to the 22q11 deletion syndrome (22q11DS). However, LCR22s are among the most complex regions in the genome, and their structure remains unresolved. The difficulty in generating accurate maps of LCR22s has also hindered localization of the deletion end points in 22q11DS patients. Using fiber FISH and Bionano optical mapping, we assembled LCR22 alleles in 187 cell lines. Our analysis uncovered an unprecedented level of variation in LCR22s, including LCR22A alleles ranging in size from 250 to 2000 kb. Further, the incidence of various LCR22 alleles varied within different populations. Additionally, the analysis of LCR22s in 22q11DS patients and their parents enabled further refinement of the rearrangement site within LCR22A and -D, which flank the 22q11 deletion. The NAHR site was localized to a 160-kb paralog shared between the LCR22A and -D in seven 22q11DS patients. Thus, we present the most comprehensive map of LCR22 variation to date. This will greatly facilitate the investigation of the role of LCR variation as a driver of 22q11 rearrangements and the phenotypic variability among 22q11DS patients.

Can CT and MRI features differentiate benign from malignant meningiomas?

AIM: To highlight magnetic resonance imaging (MRI) and computed tomography (CT) characteristics in distinguishing benign from high-grade meningiomas (World Health Organization [WHO] grade II and III) preoperatively. MATERIALS AND METHODS: Seventy-one patient who underwent surgical resection of intracranial meningiomas at American University of Beirut Medical Center between 2008 and 2017 were evaluated for various CT and MRI features. The correlation between imaging findings, histopathological grading, and operative reports was analysed via univariate and multivariate logistic regression analysis. MRI specificity and sensitivity in detecting meningioma brain invasion as compared to operative reports post-resection was detected. RESULTS: Univariate analysis results showed a significant correlation between high-grade meningiomas and several MRI features including tumour size and volume (p=0.002,0.02), heterogeneous enhancement (p<0.0001), presence of intra-tumoural necrosis (p<0.0001), ill-defined margin (p=0.003), bone erosion (p=0.004), brain invasion (p=0.001), and a higher rate of recurrence (p=0.007) Only brain invasion and presence of intra-tumoural necrosis were significantly correlated with the high-grade meningioma in multivariate analysis. Hyperostosis of the adjacent skull was the only significant CT feature predicting the presence of low-grade meningioma. MRI showed 79% specificity and 20% sensitivity, 92% negative predictive value and 7% positive predictive value in detecting meningioma brain invasion. CONCLUSION: MRI has a promising role in predicting meningioma grade prior to resection, which can directly impact patients' management protocols regarding surgical planning and complications.

BPA exposure is associated with non-monotonic alteration in ESR1 promoter methylation in peripheral blood of men and shorter relative telomere length in peripheral blood of women.

The aim of this study was to evaluate the potential association of urinary Bisphenol A (BPA) levels with estrogen receptor alpha (ESR1) promoter % methylation and relative telomere length in a sample of 482 participants. Urinary BPA concentration was measured using organic phase extraction followed by high performance liquid chromatography mass spectroscopy. Peripheral blood ESR1 promoter % methylation and relative telomere length were measured using direct bisulfite sequencing and real-time polymerase chain reaction, respectively. The mean ± SD urinary BPA concentration adjusted for urinary creatinine was 2.90 ± 4.81 (µg/g creatinine) with a median of 1.86 µg/g creatinine (min-max:

Remote ischemic conditioning in a rat model of testicular torsion: does it offer testicular protection?

BACKGROUND: Testicular torsion is a surgical emergency mainly affecting adolescent boys, with a relatively high rate of missed torsion and testicular loss secondary to delay in prompt diagnosis and surgical intervention. With ischemic reperfusion injury as its underlying culprit, testicular torsion may respond favorably to remote ischemic conditioning (RIC) where a non-privileged site (e.g. limb) is concurrently rendered ischemic to divert the cascade of reperfusion injury from the privileged organ (e.g. testicle), thus offering a protective effect in improving salvage. This mechanism is established for other organs, whereas it has not been evaluated for testis. AIM: It was aimed to evaluate RIC in a rat model of testicular torsion as a proof of principle that, similar to what has been demonstrated in other organs, RIC does offer testicular protection. STUDY DESIGN: This is an animal experimental study. Thirty Sprague-Dawley male rats were divided into control group (n = 15) and experimental group (n = 15). Non-survival surgeries of right-sided spermatic cord torsion (720° counter-clockwise twist) were performed for both the groups (45 min) followed by detorsion and reperfusion (5 min) and then orchiectomy. For the experiment group, an intervention of tail clamping to create RIC was applied 5 min after torsion, then unclamping 5 min before detorsion, followed by detorsion and reperfusion for 5 min and then orchiectomy. The testicles were histologically and immunologically examined using a hypoxia inducible factor (HIF-1α) ELISA Kit. The histological findings on ischemic changes, vascular congestion, and immunohistochemistry were quantified using previously described, validated grading systems. RESULTS: DISCUSSION: This is the first study to demonstrate the concept of RIC in an animal model of testicular torsion. It is limited by the non-availability of similar studies to compare outcomes and by the caution of extrapolating animal studies on humans. It does lay grounds, however, to subsequent studies to further elaborate on this concept and its clinical applicability. CONCLUSION: When RIC is applied in the experimental setting of testicular torsion, there is less evidence of hypoxic injury by histology and immunohistochemistry.

Association of protein intake with the outcomes of critically ill patients: a post hoc analysis of the PermiT trial.

Background: The optimal amount of protein intake in critically ill patients is uncertain. Objective: In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design: In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results: Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P < 0.0001]. There was no difference in 90-d mortality between the 2 groups [88/364 (24.2%) compared with 94/363 (25.9%), propensity score-adjusted OR: 0.80; 95% CI: 0.56, 1.16; P = 0.24]. Higher protein intake was associated with an increase in 24-h urea nitrogen excretion compared with lower protein intake, but without a significant change in prealbumin, transferrin, or 24-h nitrogen balance. Conclusions: In the PermiT trial, a moderate difference in protein intake was not associated with lower mortality. Higher protein intake was associated with increased nitrogen excretion in the urine without a corresponding change in prealbumin, transferrin, or nitrogen balance. Protein intake needs to be tested in adequately powered randomized controlled trials targeting larger differences in protein intake in high-risk populations.

Surgical outcomes among inflammatory bowel disease patients undergoing colectomy : results from a national database.

INTRODUCTION: Colectomy is relatively common in inflammatory bowel diseases (IBD), occurring more in Ulcerative Colitis (UC) as compared to Crohn's disease (CD). The surgical outcomes among this mixed population of patients are not well understood. This study aims to determine the predictors of post colectomy surgical outcomes in this patient population. METHODS: Using the National Surgical Quality Improvement Project (NSQIP) demographics, preoperative and post-operative data were analyzed for all patients undergoing colectomy for either CD or UC. Multiple variables were linked to several outcomes including mortality, anastomotic leak, and reoperation post colectomy. RESULTS: A total of 5049 IBD patients that underwent colectomy were identified. Rate of reoperation and anastomotic leak were significantly increased with steroid intake with an Odds Ratio (OR) of 1.66 (95% Confidence Interval (CI) (1.26-2.19)) and 1.81 (95%CI (1.34-2.45)) respectively. As for 30-day mortality, it was significantly lower among patients on steroid (OR=0.41; 95%CI (0.19-0.86)). Comparing UC to CD, anastomotic leaks were less common among UC patients (OR=0.53; 95%CI (0.37-0.76)), but 30-day mortality was significantly more prevalent among UC patients (OR=8.11; 95%CI (4.22-15.6)). CONCLUSION: Among IBD patients undergoing colectomy, major surgical complications except 30-day mortality appear to increase with the use of preoperative steroids.

Prevalence and characteristics of cigarillo smoking in Canada: results from the Canadian Tobacco Use Monitoring Survey.

OBJECTIVES: Cigarillo smoking has been associated with many adverse outcomes; however, little is known about its use in Canada. The aim of this study was to assess the prevalence and characteristics of ever and the current use of cigarillo in Canada. STUDY DESIGN: This study was a cross-sectional study. METHODS: This study was a secondary data analysis of the 2012 cycle of the Canadian Tobacco Use Monitoring Survey collected by Statistics Canada, examining tobacco use among Canadians aged 15 years or older in all 10 provinces. The two main outcomes of the present study were 'ever use' and 'current use' of cigarillos. Covariates examined included the following: demographic factors, socio-economic factors, and smoking-related factors. RESULTS: The overall prevalence of ever and current cigarillo smoking were 38.4% and 3.1%, respectively. Factors that had the highest association with cigarillo smoking included being a male and being young. Cigarette and marijuana use were also associated with increased use of cigarillo. Specifically, marijuana users were at two-fold increase of the current cigarillo smoking (odds ratio = 2.18, 95% confidence interval: 1.97-2.41). CONCLUSIONS: This study highlights the importance of correcting public perception about cigarillos and directing government resources to prevent an increase in their use.