The impact of sink removal and other water-free interventions in intensive care units on water-borne healthcare-associated infections: a systematic review.

With increasing awareness of water sinks as potential sources of outbreaks and transmission of multi-drug resistant (MDR) bacteria in intensive care units (ICUs), there is growing interest in water-free patient care systems. This systematic review reviewed and synthesized available evidence on the effectiveness of sink removal with or without water-free activities in the ICU environment to reduce water-borne healthcare-associated infections. We searched five databases (PubMed, MEDLINE, Scopus, Web of Science and Embase) for studies published from 1st January 1980 to 2nd April 2024 that examined water-less or water-free activities in the ICU to reduce healthcare-associated infections and patient colonization. Of 2075 articles, seven quasi-experimental studies (total: 332 patient beds) met the study selection criteria. Six of these seven studies (85.7%) were based in adult ICUs; one (14%) was in a neonatal ICU. Five of seven sites (71.4%) implemented water-less interventions after an outbreak. Water-free alternatives used included water-less bath products (six of seven; 85.7%), bottled water for consumption (three of seven; 42.9%), oral care (three of seven; 42.9%) and dissolving of oral medication (four of seven; 57.1%), designated 'contaminated' sink outside of patient and medication preparation areas for disposal of wastewater (four of seven; 57.1%). Implicated pathogens studied included MDR Gram-negative bacteria (four of seven; 57.1%), MDR Pseudomonas aeruginosa only (two of seven; 28.6%), and pulmonary non-tuberculous mycobacterium (NTB) (one of seven; 14.3%). Five of seven (71.4%) studies reported outbreak cessation. Preliminary evidence, from a limited number of studies of which the majority were conducted in an outbreak setting, suggest that sink removal and other water-free interventions in the ICU helped terminate outbreaks involving taps and decrease hospital-onset respiratory isolation of pulmonary NTB.

Randomized Trial of Postoperative Radiation Therapy After Wide Excision of Neurotropic Melanoma of the Head and Neck (RTN2 Trial 01.09).

BACKGROUND: Cutaneous neurotropic melanoma (NM) of the head and neck (H&N) is prone to local relapse, possibly due to difficulties widely excising the tumor. This trial assessed radiation therapy (RT) to the primary site after local excision. METHODS: Participants from 15 international centers were randomized to observation or RT. The participants were required to have microscopically negative excision margins 5 mm wide or wider and no evidence of disease elsewhere. The primary outcome was time to local relapse. The secondary outcomes included time to any recurrence, overall survival (OS), and toxicity. RESULTS: The trial ceased prematurely due to slow recruitment and the COVID-19 pandemic. During 2009-2020, 50 participants were randomized: 23 to observation and 27 to RT. The most common NM subsites were scalp (32%), midface (22%), and lip (20%). The median depth of invasion was 5 mm, and desmoplasia observed in 69%. The median duration from randomization to last contact was 4.8 years. Four participants (8%) experienced local relapse as a first recurrence during the study period: 3 in the observation arm and 1 in the RT arm (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.03-2.76; p = 0.279). No statistically significant difference in time to any relapse or OS was observed. More than 6 months after randomization, grade 3 or greater toxicity was experienced by 10% of the participants in the observation arm and 12.5% of the participants in the RT arm of the study. CONCLUSION: Due to low accrual, the role of adjuvant RT for cutaneous NM of the H&N excised with microscopically negative margins 5 mm wide or wider remains undefined. Its routine use cannot be recommended. Local relapse might be less common than previously anticipated based on retrospective reports.

Knowledge, attitudes, practices, and perceived challenges for healthcare workers on waterless intensive care unit (ICU) care at a neonatal ICU in Singapore.

BACKGROUND: Implementation of waterless care, including removal of sinks from patient care areas, is an emerging approach to reduce waterborne infections in high-risk areas such as intensive care units (ICUs). This approach, however, requires significant changes from traditional infection control practices and acceptance by healthcare workers (HCWs) for successful transition. AIM: To explore the knowledge, attitudes, practices (KAPs), and perceived challenges of HCWs who transitioned from working in a unit with standard infection control practices to one with waterless ICU care practices. METHODS: The study was conducted using a customized 30-item self-reported survey instrument administered to HCWs working in tertiary neonatal units at a single hospital. FINDINGS: Participation rate was 88.6% (101/114), comprising 66.3% (67/101) nurses, 31.0% (31/101) doctors, and 3.0% (3/101) allied health professionals; 90.1% (91/101) had positive attitudes and 53.5% (54/101) had good knowledge regarding waterless ICU care; 83.1% (84/101) followed the appropriate practice of hand hygiene when their hands were visibly soiled. Main challenges with waterless ICU care were perceived compromise of personal (46.5% (47/101)) and patient (22.8% (23/101)) hygiene. A total of 43.6% (44/101) reported an increase in skin-related conditions: 10.9% (11/101) had to visit a doctor for this reason, of whom 64.0% (7/11) had pre-existing skin conditions. CONCLUSION: Despite overall good attitudes and practices toward waterless ICU care, HCWs may have specific concerns related to hygiene and skin conditions which need to be addressed. For units transiting to waterless ICU care, similar surveys may provide valuable information by identifying gaps in KAP to improve compliance.

Field-Based Planetary Protection Operations for Melt Probes: Validation of Clean Access into the Blood Falls, Antarctica, Englacial Ecosystem.

Subglacial environments on Earth offer important analogs to Ocean World targets in our solar system. These unique microbial ecosystems remain understudied due to the challenges of access through thick glacial ice (tens to hundreds of meters). Additionally, sub-ice collections must be conducted in a clean manner to ensure sample integrity for downstream microbiological and geochemical analyses. We describe the field-based cleaning of a melt probe that was used to collect brine samples from within a glacier conduit at Blood Falls, Antarctica, for geomicrobiological studies. We used a thermoelectric melting probe called the IceMole that was designed to be minimally invasive in that the logistical requirements in support of drilling operations were small and the probe could be cleaned, even in a remote field setting, so as to minimize potential contamination. In our study, the exterior bioburden on the IceMole was reduced to levels measured in most clean rooms, and below that of the ice surrounding our sampling target. Potential microbial contaminants were identified during the cleaning process; however, very few were detected in the final englacial sample collected with the IceMole and were present in extremely low abundances (∼0.063% of 16S rRNA gene amplicon sequences). This cleaning protocol can help minimize contamination when working in remote field locations, support microbiological sampling of terrestrial subglacial environments using melting probes, and help inform planetary protection challenges for Ocean World analog mission concepts.

Microalgal extract as bio-coating to enhance biofilm growth of marine microalgae on microporous membranes.

Microalgal biofilm is a popular platform for algal production, nutrient removal and carbon capture; however, it suffers from significant biofilm exfoliation under shear force exposure. Hence, a biologically-safe coating made up of algal extracellular polymeric substances (EPS) was utilized to secure the biofilm cell retention and cell loading on commercial microporous membrane (polyvinylidene fluoride), making the surfaces more hydrophobic (contact angle increase up to 12°). Results demonstrated that initial cell adhesion of three marine microalgae (Amphora coffeaeformis, Cylindrotheca fusiformis and Navicula incerta) was enhanced by at least 1.3 times higher than that of pristine control within only seven days with minimized biofilm exfoliation issue due to uniform distribution of sticky transparent exopolymer particles. Bounded extracellular polysaccharide gathered was approximately 23% higher on EPS-coated membranes to improve the biofilm's hydraulic resistance, whereas bounded extracellular protein would only be substantially elevated after the attached cells re-accommodate themselves onto the EPS pre-coating of themselves. In accounting the rises of hydrophobic protein content, biofilm was believed to be more stabilized, presumably via hydrophobic interactions. EPS biocoating would generate a groundswell of interest for bioprocess intensifications though there are lots of inherent technical and molecular challenges to be further investigated in future.

Novel approach to analysis of the immune system using an ungated model of immune surface marker abundance to predict health outcomes.

Traditionally, the immune system is understood to be divided into discrete cell types that are identified via surface markers. While some cell type distinctions are no doubt discrete, others may in fact vary on a continum, and even within discrete types, differences in surface marker abundance could have functional implications. Here we propose a new way of looking at immune data, which is by looking directly at the values of the surface markers without dividing the cells into different subtypes. To assess the merit of this approach, we compared it with manual gating using cytometry data from the Singapore Longitudinal Aging Study (SLAS) database. We used two different neural networks (one for each method) to predict the presence of several health conditions. We found that the model built using raw surface marker abundance outperformed the manual gating one and we were able to identify some markers that contributed more to the predictions. This study is intended as a brief proof-of-concept and was not designed to predict health outcomes in an applied setting; nonetheless, it demonstrates that alternative methods to understand the structure of immune variation hold substantial progress.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

A pilot screening study for low bone mass in Singaporean women using years since menopause and BMI.

OBJECTIVE: Current risk assessment tools for osteoporosis have inconsistent performance across different cohorts, making them difficult for clinical practice. This study aimed to evaluate a simple screening index comprising years since menopause (YSM) and body mass index (BMI) that identifies postmenopausal Singaporean women with a greater likelihood of low bone mass. METHODS: The study used data from 188 treatment-naïve postmenopausal women. The associations between low bone mass and different demographic variables, including age, YSM and BMI, were assessed using multivariable logistic regression. Diagnostic performance of the calculated screening index was compared to the Osteoporosis Self-Assessment Tool for Asians (OSTA) and the Fracture Risk Assessment Tool (FRAX®). RESULTS: YSM and BMI were significantly associated with low bone mass. The area under the receiver operating characteristic curves was 0.803 for the screening index, 0.759 for the OSTA, 0.683 for the FRAX® (major osteoporotic fracture probability [MOFP]) and 0.647 for the FRAX® (hip fracture probability [HFP]). Non-parametric Spearman's correlation between the screening index and the other models was 0.857 with the OSTA score, 0.694 with the FRAX® (HFP) and 0.565 with the FRAX® (MOFP) (p < 0.0005). CONCLUSIONS: The diagnostic performance of the screening index comprising YSM and BMI was equivalent to the OSTA and the FRAX®. A risk chart was developed for clinicians to identify and recommend subjects for a further dual-energy X-ray absorptiometry scan. Validation of this model in larger and more diverse cohorts is required.

Repurposing Proton Beam Therapy through Novel Insights into Tumour Radioresistance.

Despite improvements in radiotherapy, radioresistance remains an important clinical challenge. Radioresistance can be mediated through enhanced DNA damage response mechanisms within the tumour or through selective pressures exerted by the tumour microenvironment (TME). The effects of the TME have in recent times gained increased attention, in part due to the success of immune modulating strategies, but also through improved understanding of the downstream effects of hypoxia and dysregulated wound healing processes on mediating radioresistance. Although we have a better appreciation of these molecular mechanisms, efforts to address them through novel combination approaches have been scarce, owing to limitations of photon therapy and concerns over toxicity. At the same time, proton beam therapy (PBT) represents an advancement in radiotherapy technologies. However, early clinical results have been mixed and the clinical strategies around optimal use and patient selection for PBT remain unclear. Here we highlight the role that PBT can play in addressing radioresistance, through better patient selection, and by providing an improved toxicity profile for integration with novel agents. We will also describe the developments around FLASH PBT. Through close examination of its normal tissue-sparing effects, we will highlight how FLASH PBT can facilitate combination strategies to tackle radioresistance by further improving toxicity profiles and by directly mediating the mechanisms of radioresistance.

Perceptions of heat-health impacts and the effects of knowledge and preventive actions by outdoor workers in Hanoi, Vietnam.

Extreme heat is an increasing climate threat, most pronounced in urban areas where poor populations are at particular risk. We analyzed heat impacts and vulnerabilities of 1027 outdoor workers who participated in a KAP survey in Hanoi, Vietnam in 2018, and the influence of their mitigation actions, their knowledge of heat-risks, and access to early warnings. We grouped respondents by their main income (vendors, builders, shippers, others, multiple jobs, and non-working) and analyzed their reported heat-health impacts, taking into consideration socioeconomics, knowledge of heat impacts and preventive measures, actions taken, access to air-conditioning, drinking amounts and use of weather forecasts. We applied linear and logistic regression analyses using R. Construction workers were younger and had less knowledge of heat-health impacts, but also reported fewer symptoms. Older females were more likely to report symptoms and visit a doctor. Access to air-conditioning in the bedroom depended on age and house ownership, but did not influence heat impacts as cooling was too expensive. Respondents who knew more heat exhaustion symptoms were more likely to report impacts (p < 0.01) or consult a doctor (p < 0.05). Similarly, those who checked weather updates were more likely to report heat impacts (p < 0.01) and experienced about 0.6 more symptoms (p < 0.01). Even though occupation type did not explain heat illness, builders knew considerably less (40%; p < 0.05) about heat than other groups but were twice as likely to consult a doctor than street vendors (p < 0.01). Knowledge of preventive actions and taking these actions both correlated positively with reporting of heat-health symptoms, while drinking water did not reduce these symptoms (p < 0.01). Child carers and homeowners experienced income losses in heatwaves (p < 0.01). The differences support directed actions, such as dissemination of educational materials and weather forecasts for construction workers. The Red Cross assisted all groups with cooling tents, provision of drinks and health advice.

Real-time kidney graft perfusion monitoring using infrared imaging during pediatric kidney transplantation.

INTRODUCTION: Ischemia times in kidney transplantation have shown to be predictive for future graft function. Preservation solutions and anticoagulation protocols have improved the management of pediatric kidney transplantation. Nonetheless, there is no current tool for intra-operative graft monitoring. The aim of this project is to present a novel technique for intra-operative real-time assessment of graft perfusion using a non-invasive infrared camera. METHODS: Prospectively, the authors included 10 pediatric patients. Surgical procedure followed their institutional protocol. Infrared imaging was captured at graft preparation, vascular anastomosis, unclamping, and at 30 s, 1, 5, and 10 min after unclamping. Analyzed variables included type of transplant, ischemia and procedure times, type of anastomosis, and results of doppler/ultrasound. Postoperative variables included creatinine levels during first 72 h. Any complications were also recorded. Delta analysis was calculated to establish the variation of temperature after unclamping. RESULTS: Average age at transplant was 9.9 years. Five cases were living donor transplants. Mean overall ischemia time was 395.6 (SD 64.4 min). Two patients had poor graft perfusion after unclamping. Of those, one had torsion of the arterial anastomosis and the other was a graft from a donor that required cardiopulmonary resuscitation for 45 min. Thermal imaging showed a correlation of 0.318 between graft temperature change and creatinine decrease. Cut-off delta for temperature for good reperfusion was above 0.2 at 1 min CONCLUSION: Real-time infrared imaging shows to be a promising option for non-invasive graft perfusion monitoring. Initial results show good correlation between intra-operative temperature changes, graft perfusion, and postoperative graft function.

Population-based trend analysis of voiding cystourethrogram ordering practices in a single-payer healthcare system before and after the release of evaluation guidelines.

INTRODUCTION: While voiding cystourethrogram (VCUG) is a widely-accepted test, it is invasive and associated with radiation exposure. Most cases of primary vesicoureteral reflux (VUR) are low-grade and unlikely to be associated with acquired renal scarring. To select patients at greatest risk, in 2011 the American Academy of Pediatrics (AAP) published guidelines for evaluation of children ages 2 - 24 months with urinary tract infections (UTIs). Similarly, in 2010 the Society for Fetal Urology (SFU) published guidelines for patients with hydronephrosis. Herein a prospectively-collected database was queried through the Institute of Clinical Evaluative Sciences (ICES), exploring trends in VCUG ordering within the Ontario Health Insurance Program (OHIP), which guarantees universal access to care. MATERIAL AND METHODS: A dedicated ICES analyst extracted data on all patients younger than 18 years in Ontario, Canada, with billing codes for VCUG and ICD-9 codes for VUR, from 2004-2014. The baseline characteristics included patient age, gender, geographic region, specialty of ordering provider and previous diagnoses of UTI and/or antenatal hydronephrosis to determine the indication for ordering the test. Of these, patients were subsequently incurred OHIP procedure codes for endoscopic injection or ureteral reimplantation. Patients who had a VCUG in the setting of urethral trauma, posterior urethral valves, and neurogenic bladder were excluded. RESULTS AND DISCUSSION: Trend analysis demonstrated that the total number of VCUGs ordered in the province has decreased over a decade (Figure 1), with a concurrent decrease in VUR diagnosis. On multivariate regression analysis, the decrease in VCUG ordering could not be explained by changes in population demographics or other baseline patient variables. Most VCUGs obtained per year were ordered by pediatricians or family physicians (mean 2,022+523.8), compared with urologists and nephrologists (mean 616+358.3). Interestingly, while the rate of VCUG requests decreased, the annual number of surgeries performed for VUR (endoscopic or open) did not show a significant reduction over time. CONCLUSIONS: We present a large population-based analysis in a universal access to care system, reporting a decreasing trend in the number of cystograms and differences by primary care versus specialist providers. While it is reassuring to see practice patterns favorably impacted by guidelines, it is also encouraging to note that the number of surgeries has remained stable. This suggests that patients at risk continue to be detected and offered surgical correction. These data confirm previous institution-based assessments and affirm changes in VCUG ordering independent of variables not relevant to the healthcare system, such as the insurance status.

The evaluation of vesicoureteral reflux among children using contrast-enhanced ultrasound: a literature review.

INTRODUCTION: Voiding cystourethrogram (VCUG) with fluoroscopy remains the gold standard for detection and evaluation of vesicoureteral reflux (VUR) among children. However, the ionizing radiation exposure remains a concern for this diagnostic modality. Recent studies have proposed using contrast-enhanced ultrasound as an alternative option for VUR screening and follow-up in children. The aim of the study was to review the literature of comparative studies that assessed the diagnostic accuracy of contrast-enhanced ultrasound compared with VCUG. METHODOLOGY: A systematic literature search was performed on electronic medical literature databases in July 2017. Literature identification, screening, and assessment of eligibility were performed by five reviewers with a pediatric radiologist. Literature was summarized for the study population, contrast used, and ultrasound mode as well as the timing of comparative reference study being performed. The studies were clustered according to the kind of contrast used. Reported diagnostic accuracy was extracted from individual studies and summarized across the included studies using descriptive statistics of median and interquartile range (IQR). RESULT: A total of 45 comparative studies were identified as eligible for the summary of the literature. Two generations of ultrasound contrast were identified in the available studies (first generation, Levovist and second generation, SonoVue). For the ultrasound studies using the first-generation contrast, the median sensitivity, regardless of the ultrasound mode, was 90.25 (IQR 83.25-97), and the median specificity was 93 (IQR 91.3-95.25). Among studies using the second-generation contrast, the median sensitivity was 86.26 (IQR 81.13-97), and the median specificity was 90.99 (IQR 84-98). No serious adverse events were reported in any of the studies. CONCLUSION: Overall, this review highlights the application of contrast-enhanced ultrasound for its advantage of no exposure to ionizing radiation and diagnostic accuracy relatively comparable to VCUG in the evaluation of VUR. In addition to the functional evaluation of the VUR, it also provides an anatomic evaluation of the kidneys and bladder with ultrasound imaging. However, one should also note that this alternate procedure is highly operator dependent where diagnostic accuracy is excellent when the expertise is available.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial.

BACKGROUND: We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy. METHODS: Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m2 D1) and 5-fluorouracil (4 g/m2 continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. RESULTS: A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717), P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%). CONCLUSION: Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.

Modified staged repair of bladder exstrophy: a strategy to prevent penile ischemia while maintaining advantage of the complete primary repair of bladder exstrophy.

INTRODUCTION: Penile ischemic injury is a reported catastrophic complication after complete primary repair of exstrophy (CPRE). Aiming to improve the bladder exstrophy-epispadias repair outcomes, the study institution adopted a modified staged exstrophy repair to incorporate the advantages of CPRE by avoiding concurrent epispadias repair and adding bilateral ureteral re-implantation and bladder neck tailoring (staged repair of bladder exstrophy with bilateral ureteral re-implantation [SRBE-BUR]) at the initial repair. It was hypothesized that such modifications minimize penile complications and prevent upper tract deterioration while enhancing bladder resistance and consequent capacity. Here, a comparative series of outcomes between CPRE and SRBE-BUR is reported. METHODS: A retrospective cohort study including all exstrophy-epispadias male neonates managed in the study institution from January 2000 to December 2014 was performed. Patients were divided into those who underwent CPRE-BUR (group 1) and SRBE-BUR (group 2) (Figure). Baseline characteristics, peri-operative data, and long-term surgical outcomes were collected and analyzed for between-group comparison. Fisher exact and Mann-Whitney U tests were performed for statistical analysis. RESULTS: A total of 21 eligible patients were included: 10 in group 1 and 11 in group 2. Baseline characteristics were comparable. Two patients in group 1 had intra-operative penile ischemic injury (one with subsequent penile tissue loss), whereas none of the group 2 patients had intra-operative complications. No significant difference between the groups was noted for operative time; however, significantly lesser blood loss was noted in group 2. Comparable long-term surgical outcomes such as additional surgical intervention, urinary continence, bladder capacity, vesicoureteral reflux, hydronephrosis and recurrent urinary tract infections (UTIs) were noted. In addition, although subjective, better penile length and cosmesis were achieved by staging the repair (Figure). CONCLUSION: The SRBE with bilateral ureteral re-implantation is a safe alternative for the repair of the exstrophy-epispadias repair as it prevents the catastrophic complication of penile tissue loss, while having comparable long-term outcomes with the CPRE. Delaying epispadias repair avoids penile injury besides possible improvement of its overall cosmesis.

Return to emergency department after pediatric urology procedures.

BACKGROUND: Unplanned postoperative return visits to the emergency department (ED) and readmission represent a quality bench outcome and pose a considerable cost burden to health-care systems. OBJECTIVE: The aim of this study is to evaluate ED return visits after pediatric urology procedures in a tertiary care children's hospital, trying to identify potential causes. This may constitute a platform for future improvement areas. MATERIALS AND METHODS: A Quality Board-approved retrospective study was performed identifying all urologic cases completed between October 2012 and September 2015. Baseline demographics, American Society of Anesthesia class, operating surgeon, type of admission, type and duration of surgical procedure, and type of anesthesia given were evaluated. Patients who returned to the ED within 30 days of the surgery date were identified. The ED records were reviewed for time of return, etiology for visit, and management received. Univariate and subsequent multivariate logistic regression statistical analyses were performed to identify variables associated with ED return. Odds ratio (OR) and 95% confidence intervals (95% CIs) were generated to determine the significance of relationships. RESULTS: Total of 4125 cases was identified. Median age was 32.9 months, with 85.1% of them being male. 349 (8.5%) cases returned to the ED within 30 days of the surgery. The majority of the returned patients, 295 (84.5%), managed conservatively with medications or reassurance, whereas 54 (15.5%) required readmission, and of those readmitted, 15 (4.3%) cases needed further surgical interventions, mainly urinary tract drainage procedures. Multivariate logistic regression analysis identified that the age, residence, admission type, inguinoscrotal surgery, and duration of surgical procedure were significantly associated with ED return (Table). The most common reason for the ED visit was UTI in 17.2%, followed by stent and catheter issues in 14.3%, wound-related in 14.3%, and bleeding in 11.7%. DISCUSSION: Pediatric literature show varying rates of ED return ranging from 2.4% to 2.6% after urologic procedures. Our return to ED rate exceeds that found in US studies, which can perhaps be attributed to the differences between the Canadian and US health-care systems. As found with other studies, age, inpatient admission, procedure type, and increased operative time were related to ED returns, possibly because of the difficulty of young children expressing themselves and the presumed complex nature of longer operations that mostly need inpatient admission. The most common reason for ED return in this study as in others was presumptive UTI. A known limitation of this study is its retrospective nature, along with the possible missed visits of patients who presented to outside hospitals. CONCLUSION: We present an account of the status of ED return visits after pediatric urology procedures in our institute. The majority of ED returns can be managed conservatively and are probably preventable.

The use of postoperative prophylactic antibiotics in stented distal hypospadias repair: a systematic review and meta-analysis.

INTRODUCTION: The current literature on the use of antibiotics perioperatively for many pediatric procedures, including hypospadias, is inconsistent. There is currently no clear evidence for the use of postoperative antibiotic prophylaxis for stented distal hypospadias repair. OBJECTIVE: This study aims to synthesize and assess the available literature on the use versus non-use of postoperative antibiotic prophylaxis for stented distal hypospadias repair. METHODOLOGY: Systematic literature search was performed on March 2018 for evaluation of trials that assessed the use and non-use of postoperative prophylactic antibiotics among stented distal hypospadias repair in children. Methodological quality of the studies was assessed according to the study design as recommended by the Cochrane Collaboration. The outcome assessed includes composite overall posthypospadias repair complications of infection and wound healing complications. The event rate for each treatment group was extracted to extrapolate intervention relative risk (RR) and corresponding 95% confidence interval (CI). Mantel-Haenszel method with random effect model was used in pooling of effect estimates from the included studies. Heterogeneity was assessed with subgroup analysis performed according to the study design. Publication bias was likewise determined. The protocol of this review was registered in PROSPERO (CRD42018087301) and reported in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULT: A total of seven studies (four cohorts, three randomized controlled trials) with 986 stented distal hypospadias repairs (408 with no post-operative prophylactic antibiotics and 578 given postoperative prophylactic antibiotics) were included for the meta-analysis. Moderate to serious risk of bias was noted among the cohort studies, while the included randomized controlled trials (RCT) were of high risk of bias. Inconsistencies of effect estimates between subgroups and publication bias with small study effect were likely present. The overall pooled effect estimates comparing treatment groups showed no significant difference for outcomes of overall composite postoperative complication (RR 0.93, 95% CI 0.45, 1.93). Assessment of composite infection related complications and wound healing complications likewise did not show any significant between-group differences (RR 1.28, 95% CI 0.49, 3.35 and RR 1.01, 95% CI 0.48, 2.12; respectively) (Table). Asymptomatic bacteriuria was noted to be significantly higher among the intervention group with no postoperative prophylactic antibiotics (RR 4.01, 95% CI 1.11, 14.54). CONCLUSION: The available evidence to date was assessed to be of high risk. The low level of evidence generated suggests that there is limited utility in the use of postoperative prophylactic antibiotics to prevent clinically significant posthypospadias repair complications.

Identification and validation of novel microenvironment-based immune molecular subgroups of head and neck squamous cell carcinoma: implications for immunotherapy.

Background: Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups. Patients and methods: A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation. Results: Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-ß signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01). Conclusions: This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.