A Leptin-regulated Circuit Controls Glucose Mobilization During Noxious Stimuli

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor–expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation

Background. Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. Methods. Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. Results. Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. Conclusions. Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratificatio

A Promising Future for Hands-On At-Home Training in Pediatric Surgery

Introduction Sufficient training is needed to acquire and retain the procedural skills needed for the surgical correction of congenital anatomical malformations. This study aims to assess the opinions of trainees and pediatric surgeons on the use of simulation-based continued at-home training, which can help to acquire these skills. Methods This study consisted of two parts. First, an international survey among trainees and pediatric surgeons assessed their opinions on simulation-based at-home training for pediatric surgical procedures (5-point Likert scale). Second, participants of pediatric colorectal courses were instructed to practice the posterior sagittal anorectoplasty procedure at-home on a simulation model and, subsequently, complete a questionnaire regarding their opinions on continuous at-home training (5-point Likert scale). Results A total of 163 participants (83% pediatric surgeons) completed the international survey (response rate 43%). Overall, participants considered the training useful for both laparoscopic (mean 4.7) and open procedures (mean 4.2) and agreed that it may be used at home after a hands-on course (mean 4.3). Twenty participants completed the questionnaire on continued training (response rate 36%). All agreed that at-home training was of added value (mean 4.5) and that the skills were transferable to the clinical setting (mean 4.3). At-home training was regarded a suitable exercise after a hands-on workshop (mean 4.3), but less so without a workshop (mean 3.7, p =0.017). Conclusion Participating trainees and pediatric surgeons were of the opinion that simulation models and at-home training have added value. This implies that simulation-based training may be used more often in pediatric surgical training

The value of routine ultrasound at discharge to identify patients at risk of developing symptomatic lymphoceles after kidney transplantation: A case-cohort study

Introduction: Ultrasound examination is frequently used to evaluate the graft after renal transplantation and to detect possible lymphoceles. The first ultrasound scan in our hospital is normally performed on the day of discharge. We questioned whether perirenal fluid collections detected by ultrasound examination at discharge are predictive for future symptomatic lymphoceles. Methods: All ultrasound reports of all renal transplant recipients treated in our hospital between January 2010 and December 2017 were collected and screened for abnormalities such as fluid collections. Patients that developed a symptomatic lymphocele were compared with a control group from the same cohort. Sensitivity and specificity of ultrasound examination to detect symptomatic lymphoceles were calculated for the primary and consecutive ultrasounds tests. Results: There were no significant differences at baseline characteristics between the Symptomatic lymphocele group and control group, with the exception of mean age at kidney transplantation (47 ± 17 years in the control group vs. 56 ± 13 years in the symptomatic lymphocele group, p=0.02). The ultrasound examination at discharge had a sensitivity of 31% and specificity of 87% to detect future symptomatic lymphoceles. The positive predictive value was only 10%. The second ultrasound test had the best test variables to detect symptomatic lymphoceles with a sensitivity of 93% and a specificity of 87% and a predictive value of 28%. Conclusion: Routinely use of ultrasound testing on the day of discharge does detect perirenal fluid collections, but is not predictive for development of symptomatic lymphoceles in the future

Development and validation of a condition-specific quality of life instrument for adults with esophageal atresia: the SQEA questionnaire

The importance of multidisciplinary long-term follow-up for adults born with esophageal atresia (EA) is increasingly recognized. Hence, a valid, condition-specific instrument to measure health-related quality of life (HRQoL) becomes imperative. This study aimed to develop and validate such an instrument for adults with EA. The Specific Quality of life in Esophageal atresia Adults (SQEA) questionnaire was developed through focus group-based item generation, pilot testing, item reduction and a multicenter, nationwide field test to evaluate the feasibility, reliability (internal and retest) and validity (structural, construct, criterion and convergent), in compliance with the consensus-based standards for the selection of health measurement instruments guidelines. After pilot testing (n = 42), items were reduced from 144 to 36 questions. After field testing (n = 447), three items were discarded based on item-response theory results. The final SQEA questionnaire (33 items) forms a unidimensional scale generating an unweighted total score. Feasibility, internal reliability (Cronbach's alpha 0.94) and test-retest agreement (intra-class coefficient 0.92) were good. Construct validity was discriminative for esophageal replacement (P < 0.001), dysphagia (P < 0.001) and airway obstruction (P = 0.029). Criterion validity showed a good correlation with dysphagia (area under the receiver operating characteristic 0.736). SQEA scores correlated well with other validated disease-specific HRQoL scales such as the GIQLI and SGRQ, but poorly with the more generic RAND-36. Overall, this first condition-specific instrument for EA adults showed satisfactory feasibility, reliability and validity. Additionally, it shows discriminative ability to detect disease burden. Therefore, the SQEA questionnaire is both a valid instrument to assess the HRQoL in EA adults and an interesting signaling tool, enabling clinicians to recognize more severely affected patients

Psychometric Performance of a Condition-Specific Quality-of-Life Instrument for Dutch Children Born with Esophageal Atresia

A condition-specific instrument (EA-QOL&copy;) to assess quality of life of children born with esophageal atresia (EA) was developed in Sweden and Germany. Before implementing this in the Netherlands, we evaluated its psychometric performance in Dutch children. After Swedish&ndash;Dutch translation, cognitive debriefing was conducted with a subset of EA patients and their parents. Next, feasibility, reliability, and validity were evaluated in a nationwide field test. Cognitive debriefing confirmed the predefined concepts, although some questions were not generally applicable. Feasibility was poor to moderate. In 2-to-7-year-old children, 8/17 items had &gt;5% missing values. In 8-to-17-year-old children, this concerned 3/24 items of the proxy-report and 5/14 items of the self-report. The internal reliability was good. The retest reliability showed good correlation. The comparison reliability between self-reports and proxy-reports was strong. The construct validity was discriminative. The convergent validity was strong for the 2-to-7-year-old proxy-report, and weak to moderate for the 8-to-17-year-old proxy-report and self-report. In conclusion, the Dutch-translated EA-QOL questionnaires showed good reliability and validity. Feasibility was likely affected by items not deemed applicable to an individual child&rsquo;s situation. Computer adaptive testing could be a potential solution to customizing the questionnaire to the individual patient. Furthermore, cross-cultural validation studies and implementation-evaluation studies in different countries are needed

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially