Two-stage repair of low anorectal malformations in girls: is it truly a setback?

Background/purpose Anorectal malformations (ARMs) affect 1 in 4000–5000 births. Low ARMs are nowadays treated in the first stage rather than at second or third stages. However, reports suggest problems with continence in these children because of wound dehiscence and infection; thus, protective colostomy may still be recommended. Colostomies do have complications, but the question is whether these disadvantages outweigh the protective effect on wound healing after anal reconstruction. The aim of this study was to define whether two-stage repair of low ARMs in girls is truly a setback or whether it is beneficial.Patients and methods During the period of June 2008–June 2012, 30 female patients suffering from low ARMs were admitted to Mansoura University Children Hospital. Their ages at the time of surgery ranged from 3 to 11 months (mean age 6.2) and they were divided into two equal groups. The fistula location was defined either anocutaneous or anovestibular according to the Pena classification. The choice of management was totally randomized; thus, patients of group A underwent a two-stage posterior sagittal anorectoplasty and group B patients underwent a one-stage posterior sagittal anorectoplasty operation. Data recorded included age, fistula location, associated anomalies, operation performed, operative time, length of hospital stay, approximate cost, and postoperative complications.Results A comparison of data showed that treatment of patients of group A involved more time and money and they had a longer duration of hospital stay than did patients of group B. Seven patients (47%) in group A and nine patients (60%) in group B showed postoperative complications. Wound infection occurred in three patients (20%) of group A and in eight patients (53%) of group B. More importantly, two (13%) wound disruptions occurred among the three cases with wound infection in group A, whereas six (40%) disruptions occurred among the eight patients (53%) with wound infections in group B. The incidence of redo operation in group B was found to be significantly higher than in group A. Mucosal prolapse occurred in only one patient (7%) of group B. Complications related to colostomy occurred in group A only; five patients (33%) suffered skin excoriation around the stoma and one patient (7%) showed a prolapsed distal stoma loop. Constipation was noted during follow-up in five patients (33%) of group A and in six patients (40%) of group B.Conclusion Two-stage repair of low ARM in girls is truly beneficial, as we could perform a successful operation and achieve continence in the child regardless of the complications of colostomy, which are temporary and tolerable.Keywords: anorectal malformations, colostomy, posterior sagittal anorectoplasty, two-stage repair of low anorectal malformatio

Detrusor wall thickness compared to other non-invasive methods in diagnosing men with bladder outlet obstruction: A prospective controlled study

AbstractIntroductionThe current study aims to compare the diagnostic accuracy of detrusor wall thickness to other noninvasive, tools, using pressure flow studies as a reference, in the assessment of bladder outlet, obstruction among men presenting with lower urinary tract symptoms.Patients and MethodsMen aged 50 or older presenting with lower urinary tract symptoms were evaluated for bladder outlet, obstruction using detrusor wall thickness (measured by a transabdominal 7.5MHz ultrasound) and, other non-invasive tools (namely uroflowmetry, post-void residual, and prostate volume), and the results were compared to pressure flow study.ResultsDetrusor wall thickness ranged from 0.7mm to 7mm (mean±SD of 2.39±1.64mm), and 21 patients, were classified as obstructed (thickness≥2mm). Based on pressure flow study 23 patients had, bladder outlet obstruction. Detrusor wall thickness had the highest accuracy (88.0%), the highest, specificity (92.6%) and the highest positive predictive value (90.5%) among the non-invasive tests.ConclusionsDetrusor wall thickness measurement can be used to diagnose and quantify bladder outlet obstruction, non-invasively in men with lower urinary tract symptoms, with an accuracy approaching that of the standard pressure flow studies

Illuminating Host-Parasite Interaction at the Cellular and Subcellular Levels with Infrared Microspectroscopy

Toxoplasma gondii (T. gondii) is an opportunistic protozoan that can cause brain infection and other serious health consequences in immuno-compromised individuals. This parasite has a remarkable ability to cross biological barriers and exploit the host cell microenvironment to support its own survival and growth. Recent advances in label-free spectroscopic imaging techniques have made it possible to study biological systems at a high spatial resolution. In this study, we used conventional Fourier-transform infrared (FTIR) microspectroscopy and synchrotron-based FTIR microspectroscopy to analyze the chemical changes that are associated with infection of human brain microvascular endothelial cells (hBMECs) by T. gondii (RH) tachyzoites. Both FTIR microspectroscopic methods showed utility in revealing the chemical alterations in the infected hBMECs. Using a ZnS hemisphere device, to increase the numerical aperture, and the synchrotron source to increase the brightness, we obtained spatially resolved spectra from within a single cell. The spectra extracted from the nucleus and cytosol containing the tachyzoites were clearly distinguished. RNA sequencing analysis of T. gondii-infected and uninfected hBMECs revealed significant changes in the expression of host cell genes and pathways in response to T. gondii infection. These FTIR spectroscopic and transcriptomic findings provide significant insight into the molecular changes that occur in hBMECs during T. gondii infection

Marine integrons containing novel integrase genes, attachment sites, attI, and associated gene cassettes in polluted sediments from Suez and Tokyo Bays

In order to understand the structure and biological significance of integrons and associated gene cassettes in marine polluted sediments, metagenomic DNAs were extracted from sites at Suez and Tokyo Bays. PCR amplicons containing new integrase genes, intI, linked with novel gene cassettes, were recovered and had sizes from 1.8 to 2.5 kb. This approach uncovered, for the first time, the structure and diversity of both marine integron attachment site, attI, and the first gene cassette, the most efficiently expressed integron-associated gene cassette. The recovered 13 and 20 intI phylotypes, from Suez and Tokyo Bay samples, respectively, showed a highly divergence, suggesting a difference in integron composition between the sampling sites. Some intI phylotypes showed similarity with that from Geobacter metallireducens, belonging to Deltaproteobacteria, the dominant class in both sampling sites, as determined by 16S rRNA gene analysis. Thirty distinct families of putative attI site, as determined by the presence of an attI-like simple site, were recovered. A total of 146 and 68 gene cassettes represented Suez and Tokyo Bay unsaturated cassette pools, respectively. Gene cassettes, including a first cassette, from both sampling sites encoded two novel families of glyoxalase/bleomycin antibiotic-resistance protein. Gene cassettes from Suez Bay encoded proteins similar to haloacid dehalogenases, protein disulfide isomerases and death-on-curing and plasmid maintenance system killer proteins. First gene cassettes from Tokyo Bay encoded a xenobiotic-degrading protein, cardiolipin synthetase, esterase and WD40-like β propeller protein. Many of the first gene cassettes encoded proteins with no ascribable function but some of them were duplicated and possessed signal functional sites, suggesting efficient adaptive functions to their bacterial sources. Thus, each sampling site had a specific profile of integrons and cassette types consistent with the hypothesis that the environment shapes the genome

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Crystal Structure of an Integron Gene Cassette-Associated Protein from Vibrio cholerae Identifies a Cationic Drug-Binding Module

Background The direct isolation of integron gene cassettes from cultivated and environmental microbial sources allows an assessment of the impact of the integron/gene cassette system on the emergence of new phenotypes, such as drug resistance or virulence. A structural approach is being exploited to investigate the modularity and function of novel integron gene cassettes. Methodology/Principal Findings We report the 1.8 A crystal structure of Cass2, an integron-associated protein derived from an environmental V. cholerae. The structure defines a monomeric beta-barrel protein with a fold related to the effector-binding portion of AraC/XylS transcription activators. The closest homologs of Cass2 are multi-drug binding proteins, such as BmrR. Consistent with this, a binding pocket made up of hydrophobic residues and a single glutamate side chain is evident in Cass2, occupied in the crystal form by polyethylene glycol. Fluorescence assays demonstrate that Cass2 is capable of binding cationic drug compounds with submicromolar affinity. The Cass2 module possesses a protein interaction surface proximal to its drug-binding cavity with features homologous to those seen in multi-domain transcriptional regulators. Conclusions/Significance Genetic analysis identifies Cass2 to be representative of a larger family of independent effector-binding proteins associated with lateral gene transfer within Vibrio and closely-related species. We propose that the Cass2 family not only has capacity to form functional transcription regulator complexes, but represents possible evolutionary precursors to multi-domain regulators associated with cationic drug compounds.National Health and Medical Research Council (Australia) (NHMRC grant 488502)National Institutes of Health (U.S.) (Grant GM62414-0 )Ontario. Ministry of Revenue (Challenge Fund

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Neuropsychological function is related to irritable bowel syndrome in women with premenstrual syndrome and dysmenorrhea

Background There is increasing evidence demonstrating the co-occurrence of primary dysmenorrhea (PD), premenstrual syndrome (PMS), and irritable bowel syndrome (IBS) in women. This study aimed to investigate whether women who have symptoms of IBS in addition to PD and PMS also report more severe or frequent menstruation-associated symptoms and psychological complications compared to women with PD and PMS alone. Methods The study group included 182 female University students aged 18–25 years. IBS was diagnosed using the Rome III criteria. The severity of PMS and PD was determined using a 10-point visual analog scale and PSST (Premenstrual Syndrome Screening Tool), respectively. Neuropsychological functions including cognitive function, depression score, anxiety score, stress, insomnia, daytime sleepiness, quality of life and personality were assessed using standard questionnaires. Results Of the 182 young females, 31 (17.0%) had IBS. Average days of bleeding during the menstrual cycle and mean pain severity on the PSST scale were significantly greater in the group with IBS compared to the non-IBS group (p < 0.01). The non-IBS individuals scored more favorably than the women with IBS with respect to severity of depression, insomnia, daytime sleepiness (p < 0.05). The PSST scores were significantly correlated with scores for depression (r = 0.29; p < 0.001), anxiety (r = 0.28; p < 0.001), stress (r = 0.32; p < 0.001), insomnia (r = 0.34; p < 0.001) and daytime sleepiness (r = 0.31; p < 0.001); while, they were negatively correlated with cognitive abilities (r = − 0.20; p = 0.006) and quality of life (r = − 0.42; p < 0.001). Linear regression analysis showed that the PSST scores were possibly significant factors in determining the scores for depression, anxiety, stress, quality of life, insomnia and daytime sleepiness (p < 0.05). Conclusion IBS is related to psychological comorbidities, in particular depression, sleep problems and menstrual-associated disorders. IBS may exacerbate the features of PMS which should be taken into account in the management of PMS