Citations

Background/aim To determine if Boys Bantam and Peewee and Girls U14 sustain fewer concussions, head hits, ‘other injuries’ and penalties in hockey tournaments governed by intensified fair play (IFP) than non-intensified fair play (NIFP). Methods A prospective comparison of IFP, a behaviour modification programme that promotes sportsmanship, versus control (non-intensified, NIFP) effects on numbers of diagnosed concussions, head hits without diagnosed concussion (HHWDC), ‘other injuries’, number of penalties and fair play points (FPPs). 1514 players, ages 11–14 years, in 6 IFP (N=950) and 5 NIFP (N=564) tournaments were studied. Results Two diagnosed concussions, four HHWDC, and six ‘other injuries’ occurred in IFP tournaments compared to one concussion, eight HHWDC and five ‘other injuries’ in NIFP. There were significantly fewer HHWDC in IFP than NIFP (p=0.018). However, diagnosed concussions, ‘other injuries’, penalties and FPPs did not differ significantly between conditions. In IFP, a minority of teams forfeited the majority of FPPs. Most diagnosed concussions, HHWDC, and other injuries occurred to Bantam B players and usually in penalised teams that forfeited their FPPs. Conclusions In response to significant differences in HHWDC between IFP and NIFP tournaments, the following considerations are encouraged: mandatory implementation of fair play in regular season and tournaments, empowering tournament directors to not accept heavily penalised teams, and introducing ‘no body checking’ in Bantam.

Abstract Introduction: Few studies have assessed the impact of obesity on laparoscopic cholecystectomy (LC) in pediatric patients. Materials and Methods: Children who underwent LC were identified from the 2012 to 2013 American College of Surgeons' National Surgical Quality Improvement Program Pediatrics data. Patient characteristics, operative details, and outcomes were compared. Multivariable logistic regression was utilized to identify predictors of increased operative time (OT) and duration of anesthesia (DOAn). Results: In total, 1757 patients were identified. Due to low rates of obesity in children <9 years old, analyses were limited to those 9–17 ( n = 1611, 43% obese). Among obese children, 80.6% were girls. A higher proportion of obese patients had diabetes (3.0% versus 1.0%, P < .01) and contaminated or dirty/infected wounds (15.1% versus 9.4%, P < .01). Complication rates were low. The most frequent indications for surgery were cholelithiasis/biliary colic (34.3%), chronic cholecystitis (26.9%), and biliary dyskinesia (18.2%). On multivariable analysis, obesity was an independent predictor of OT >90 (odds ratio [OR] 2.02; 95% confidence interval [95% CI] 1.55–2.63), and DOAn >140 minutes (OR 1.86; 95% CI 1.42–2.43). Conclusions: Obesity is an independent risk factor for increased OT in children undergoing LC. Pediatric surgeons and anesthesiologists should be prepared for the technical and physiological challenges that obesity may pose in this patient population.

Background Historically, lumbar drains (LD) have played a prominent role in endonasal skull base surgery. Over the past few decades, advancements in techniques have augmented our ability to successfully reconstruct complex skull base defects and often obviates the need for cerebrospinal fluid (CSF) diversion. Clarity on the appropriate use of LDs is needed. Objective To examine the literature for the need for LDs in contemporary skull base reconstruction after resection of skull base tumors. Methods A systematic literature review of English language articles by using PubMed and Ovid. Search terms included “lumbar drain,” “CSF leak,” and “endoscopic endonasal reconstruction.” Articles were included when they pertained to adults, used current methods for reconstruction (i.e., multilayered repair or vascularized tissue), and addressed CSF leak rates secondary to endoscopic resection of skull base masses. All the studies discussed CSF leaks that resulted from traumatic-, idiopathic-, or sinus surgery-related iatrogenic causes were excluded. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Results A total of five articles met inclusion criteria. These comprised 376 endoscopic skull base tumor resection and reconstruction cases; 5.59% developed postoperative CSF leaks. A meta-analysis was conducted by incorporating three studies that met criteria based on testing for heterogeneity. The average odds ratio for postoperative CSF leak for patients who did not have an LD relative to patients who had an LD was 0.590 (95% confidence interval, 0.214–1.630). Given a p value of 0.30, the results demonstrated a lack of statistically significant improvement between patients who had an LD and patients who did not have an LD. Various details, such as the defect size and type of CSF leak, were not consistently reported among studies. Conclusions Available evidence for the use of LDs in skull base surgery is of poor quality. Analysis of the literature revealed heterogenous and varied reporting in the primary literature. Further studies that include randomized controlled trials are needed.

Abstract Purpose of the Study Middle-aged adults are often called upon to support aging parents. However, providing support to an aging parent with health problems and disability may be a stressful experience. This study asked whether giving everyday support to parents in the context of health problems and disability has implications for middle-aged children’s diurnal cortisol and daily mood. Design and Methods During four consecutive days, 148 middle-aged adults (mean age = 55) reported the support they gave to their parents and provided saliva 4 times a day (wake, 30 min post-wake, lunchtime, and bedtime). Multilevel models estimated within-person differences in positive affect (PA) and negative affect (NA), cortisol awakening response and area under the curve with respect to ground (AUC-G) as a function of giving same-day and previous-day support. We examined whether these associations are exacerbated when a parent has health problems or activities of daily living (ADL) needs. Results Middle-aged children had significantly higher next-day AUC-G on days after they gave support to parents with ADL needs. When participants gave support to parents with ADL needs, they had significantly greater same-day PA and lower next-day NA. Giving support to parents with health problems was associated with significantly higher next-day NA. Implications Giving support to parents is an ambiguous experience with implications for biological stress and daily mood. A biopsychosocial approach reveals under what conditions giving support to parents may become detrimental to health and well-being; this knowledge is essential for the development and implementation of interventions.

Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathologic findings, we performed a retrospective search of the patient and pathologic databases of Mayo Clinic in Rochester, MN, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had clinical, pathologic, or laboratory evidence of an adrenocortical disorder. Seventeen had classic CS; 15 underwent bilateral, subtotal, or partial unilateral adrenalectomy, and 2 had no treatment. Pathologically, the glands were normal sized or slightly enlarged with multiple small (1 to 4 mm), brown, black, and yellow micronodules (primary pigmented nodular adrenocortical disease; PPNAD). Three glands each had a mass: a 2 cm adenoma, a 1.5 cm macronodule, and an unencapsulated 1.8 cm myelolipoma. Fourteen of the patients were alive at follow-up, and 3 were deceased; 2 of the latter had PPNAD at autopsy, and the third had PPNAD at surgery. Twelve patients without clinical features of classic CS had abnormal adrenocortical testing results; none developed classic CS during follow-up (mean, 10 y). Autopsy findings in 1 showed bilateral vacuolated cell cortical hyperplasia.

Abstract Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo. The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632–45. ©2016 AACR.

Abstract Clinical trial Data and Safety Monitoring Boards (DSMBs) have a primary obligation of ensuring study participant safety, while maintaining trial integrity. The role of DSMBs is expanding, and ideally should include post-hoc reporting of deliberative processes related to clinically important safety issues or factors that could impact on future trial designs. We describe how the TOPCAT DSMB detected, investigated, and adjudicated an unexpectedly large renal adverse event signal midway through the trial, and offer general guidelines for dealing with similar unanticipated occurrences in future trials. The detection of a greater than expected incidence of deterioration in renal function, occurring in 6.1% of patients in the spironolactone arm compared with 3.9% in the placebo arm (P = 0.009), led to an in-depth DSMB review of associated study medication withdrawals and adverse events. The trial continued uninterrupted throughout the review, which reached the conclusions that spironolactone-associated renal dysfunction did not compromise overall patient safety or interfere with a perceived efficacy signal. Although no discrete mechanism for the spironolactone-associated renal adverse event signal was identified, likely possibilities are discussed. In clinical trials, DSMBs and co-ordinating centres should have the resources to detect, investigate, and adjudicate unexpected safety issues, with goals of ensuring patient safety and preserving the potential for detection of therapeutic effectiveness. In TOPCAT, spironolactone-associated renal dysfunction emerged as a potentially trial-threatening adverse event and, although clinically important, did not lead to compromise of patient safety, trial interruption, termination, or apparent loss of treatment effectiveness.

Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase–isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase–isomaltase ( SI ) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case–control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.

Pharmacogenomics, studying genetic variation related to drug response, was established decades ago. Today, performing clinical pharmacogenomics testing has increased, creating great potential to improve patient care. Yet widespread implementation of pharmacogenomics in practice is currently limited, resulting in the “therapeutic odyssey” of patients. Preemptive clinical pharmacogenomics testing prior to the time of prescribing is now emerging as an option that could tailor the pharmacotherapy of patients by increasing drug effectiveness while reducing adverse drug reaction risk.