Bacteria and viruses and their role in the preschool wheeze to asthma transition.

Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or recurrent disease. Early-life wheezing and asthma exacerbations are triggered by common respiratory viruses, mainly rhinoviruses (RV), and to a lesser extent, respiratory syncytial virus, parainfluenza, human metapneumovirus, coronaviruses, adenoviruses, influenza, and bocavirus. The excess presence of bacteria, several of which are part of the microbiome, has also been identified in association with wheezing and acute asthma exacerbations, including haemophilus influenza, streptococcus pneumoniae, moraxella catarrhalis, mycoplasma pneumoniae, and chlamydophila pneumonia. While it is not clear when asthma starts, its characteristics develop over time. Airway remodeling already appears between the ages of 1 and 3 years of age even prior to the presence of atopic inflammation or an asthma diagnosis. The role of genetic defect or variations hampering the airway epithelium in response to environmental stimuli and severe disease morbidity are now considered as major determinants for early structural changes. Repeated viral infections can induce and perpetuate airway hyperresponsiveness. Allergic sensitization, that often precedes infection-induced wheezing, shifts inflammation toward type-2, while common respiratory infections themselves promote type-2 inflammation. Nevertheless, most children who wheeze with viral infections during infancy and during preschool years do not develop persistent asthma. Multiple factors, including illness severity, viral etiology, allergic sensitization, and the exposome, are associated with disease persistence. Here, we summarize current knowledge and developments in infection epidemiology of asthma in children, describing the known impact of each individual agent and mechanisms of transition from recurrent wheeze to asthma.

Assessing the need for adenotonsillectomy for sleep-disordered breathing in a community setting: A secondary outcome measures analysis of a randomized controlled study.

OBJECTIVE: To assess whether children with sleep-disordered breathing (SDB) symptom severity above a certain level, measured by a validated questionnaire, improve after adenotonsillectomy (AT) compared to no intervention. METHODS: Children with snoring and tonsillar hypertrophy (4 to 10-years old), who were candidates for AT, were randomly assigned to two evaluation sequences (baseline and 3-month follow-up): (a) evaluation immediately before AT and at 3 months postoperatively (AT group); or (b) evaluation at the initial visit and at the end of the usual 3-month waiting period for surgery (control group). Outcomes were (a) Pediatric Sleep Questionnaire sleep-related breathing disorder scale (PSQ-SRBD); (b) modified Epworth Sleepiness Scale (mESS); and (c) proportion of subjects achieving PSQ-SRBD <0.33 (low-risk for apnea-hypopnea index ≥5/h) if they had score ≥0.33 at baseline. RESULTS: Sixty-eight children were assigned to the AT and 72 to the control group and two-thirds of them had PSQ-SRBD ≥0.33. The AT group experienced significantly larger improvement between follow-up and baseline than controls (between-group difference [95% CI] for PSQ-SRBD: -0.31 [-0.35 to -0.27]; and mESS: -2.76 [-3.63 to -1.90]; P < .001 for both). Children with baseline PSQ-SRBD ≥0.33 in the AT group had an eight-times higher probability of achieving PSQ-SRBD <0.33 at follow-up than controls with similar baseline score (risk ratio [95% CI]: 8.33 [3.92-17.54]; P < .001). CONCLUSION: Among children with snoring, tonsillar hypertrophy, and clinical indications for AT, those with preoperative PSQ-SRBD score ≥0.33 show measurable clinical benefit postoperatively.

Palliative surgical bypass is superior to palliative endoscopic stenting in patients with malignant gastric outlet obstruction: systematic review and meta-analysis.

BACKGROUND: Gastrojejunostomy (GJ) and self-expanding metal stents (SEMS) are the two most common palliative treatment options for patients with malignant gastric outlet obstruction (GOO). Randomised trials and retrospective studies have shown discrepant results, so that there is still a controversy regarding the optimal treatment of GOO. METHODS: Medline, Web of Science and Cochrane Library were systematically searched for studies comparing GJ to SEMS in patients with malignant GOO. Primary outcomes were survival and postoperative mortality. Secondary outcomes were frequency of re-interventions, major complications, time to oral intake and length of hospital stay. RESULTS: Twenty-seven studies, with a total of 2.354 patients, 1.306 (55.5%) patients in the SEMS and 1.048 (44.5%) patients in the GJ group, were considered suitable for inclusion. GJ was associated with significantly longer survival than SEMS (mean difference 43 days, CI 12.00, 73.70, p = 0.006). Postoperative mortality (OR 0.55, CI 0.27, 1.16, p = 0.12) and major complications (OR 0.73, CI 0.5, 1.06, p = 0.10) were similar in both groups. The frequency of re-interventions, however, was almost three times higher in the SEMS group (OR 2.95, CI: 1.70, 5.14, p < 0.001), whereas the mean time to oral intake and length of hospital stay were shorter in the SEMS group (mean differences - 5 days, CI - 6.75, - 3.05 days, p < 0.001 and - 10 days, CI - 11.6, - 7.9 days, p < 0.001, respectively). CONCLUSIONS: Patients with malignant GOO and acceptable performance status should be primarily considered for a palliative GJ rather than SEMS.

Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with pancreatic cancer: Systematic review and meta-analysis.

BACKROUND: The role of sarcopenia and sarcopenic obesity in patients with pancreatic ductal adenocarcinoma(PDAC) remains controversial. MATERIAL AND METHODS: Medline and Web of Science were searched for studies reporting survival in sarcopenic and/or sarcopenic obese patients with pancreatic cancer. Primary outcome was mortality in patients with sarcopenia and/or sarcopenic obesity versus non-sarcopenic and/or non-sarcopenic obese patients. Secondary outcome was the incidence of major postoperative complications. RESULTS: Eleven studies comprising 2.297 patients were considered suitable for inclusion. Overall 959 of 2.111(45.4%) patients were defined as sarcopenic and 163 of 1.254(13%) as sarcopenic obese. Patients' age was above 60 years(range 63-69) with a male proportion ranging from 50.8% to 68.0%. Of 2.297 patients, 958(41.7%) underwent palliative treatment, 1.339(58.3%) curative resections. Follow-up ranged from 11 to 57.7 months. Median overall survival ranged from 4.3 to 12 months in palliative patients and 17.4 to 25.8 months after curative resection. Overall proportions of sarcopenic patients varied from 21.3% to 65.3%. Sarcopenia was significantly associated with poorer overall survival(HR 1.49; 95%CI 1.27-1.74,p<0.001). Sarcopenic obesity was reported in 0.6% to 25.0% of patients, and was also significantly associated with poorer overall survival(HR 2.01; 95%CI 1.55-2.61,p<0.001). The incidence of major complications ranged from 8.6% to 33.9%. Rates of clinically relevant(grade B/C) postoperative pancreatic fistulas varied from 8.3% to 17.8%. Sarcopenic obesity was an independent predictor of major postoperative complications in one study, in another study sarcopenia was significantly associated with clinically relevant pancreatic fistulas. CONCLUSIONS: Sarcopenia and sarcopenic obesity are significantly associated with poorer overall survival in patients with PDAC.

Use of Oximetry to Determine Need for Adenotonsillectomy for Sleep-Disordered Breathing.

: media-1vid110.1542/5802711151001PEDS-VA_2017-3382Video Abstract OBJECTIVES: We evaluated the efficacy of adenotonsillectomy (T/A) in children with sleep-disordered breathing (SDB) in a controlled study using oximetry. We hypothesized that children with SDB and abnormal nocturnal oximetry in a community setting will have improved hypoxemia indices after T/A. METHODS: Children with snoring and tonsillar hypertrophy (4-10 years old) who were candidates for T/A were randomly assigned to 2 oximetry sequences (baseline and 3-month follow-up): (1) oximetry immediately before T/A and at the 3-month follow-up, which occurred postoperatively (T/A group); or (2) oximetry at the initial visit and at the end of the usual 3-month waiting period for surgery (control group). Outcomes were (1) proportion of subjects with McGill oximetry score (MOS) >1 at baseline acquiring MOS of 1 at follow-up and (2) proportion of subjects achieving oxygen desaturation (≥3%) of hemoglobin index (ODI3) <2 episodes per hour at follow-up if they had ODI3 ≥3.5 episodes per hour at baseline. RESULTS: One hundred and forty children had quality oximetry tracings. Twelve of 17 (70.6%) children with MOS >1 in the T/A group and 10 of 21 (47.6%) children with MOS >1 in the control group had MOS of 1 at follow-up (P = .14). More subjects in the T/A than in the control group achieved ODI3 <2 episodes per hour at follow-up (14 of 32 [43.8%] vs 2 of 38 [5.3%]; P < .001). Three children with elevated ODI3 were treated to prevent persistently abnormal ODI3 in 1 child at follow-up. CONCLUSIONS: An ODI3 ≥3.5 episodes per hour in nocturnal oximetry is related to increased resolution rate of nocturnal hypoxemia after T/A for SDB compared with no intervention.

Effect of allergic bronchopulmonary aspergillosis on FEV1 in children and adolescents with cystic fibrosis: a European Cystic Fibrosis Society Patient Registry analysis.

OBJECTIVE: To evaluate the effect of allergic bronchopulmonary aspergillosis (ABPA) on FEV1 percent predicted in children and adolescents with cystic fibrosis. DESIGN: Longitudinal data analysis (2008-2010). SETTING: Patients participating in the European Cystic Fibrosis Society Patient Registry. PARTICIPANTS: 3350 patients aged 6-17 years. MAIN OUTCOME MEASURE: FEV1 percent predicted was the main outcome measure (one measurement per year per child). To describe the effect of ABPA (main explanatory variable) on FEV1 while controlling for other prognostic factors, a linear mixed effects regression model was applied. RESULTS: In 2008, the mean (±SD) FEV1 percent predicted was 78.6 (±20.6) in patients with ABPA (n=346) and 88 (±19.8) in those without ABPA (n=2806). After considering other variables, FEV1 in subjects with ABPA on entry to the study was 1.47 percentage points lower than FEV1 in patients of similar age without ABPA (p=0.003). There was no FEV1 decline associated with ABPA over the subsequent study years as the interaction of ABPA with age was not significant (p>0.05). For patients aged 11.82 years (population mean age), poor body mass index had the greatest impact on FEV1 in 2008, followed by high-risk genotype (two severe mutations), female gender, diabetes mellitus, chronic Pseudomonas aeruginosa infection and ABPA in descending order of effect size. CONCLUSIONS: In contrast to the common clinical belief of ABPA having a serious impact on lung function, the difference in FEV1 between young patients with and without the complication was found to be modest when the effect of other prognostic factors was considered.

High risk of fistula formation in vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis-a retrospective analysis.

PURPOSE: The aim of this study was to evaluate the efficacy of vacuum-assisted closure therapy in patients with open abdomen due to secondary peritonitis and to identify possible risk factors of fistula formation. METHODS: The hospital OPS-database (time period 2005-2014) was searched to identify patients treated with an open abdomen due to secondary peritonitis, who underwent vacuum-assisted closure therapy. Medical records were retrospectively analyzed for patients' characteristics, cause of peritonitis, duration of vacuum therapy, number of relaparotomies, fascial closure rates, and risk factors of fistula formation. RESULTS: Forty-three patients (19 male, 24 female) with a median age of 65 years (range 24-90 years) were identified. The major cause of secondary peritonitis was anastomotic leakage after intestinal anastomosis or bowel perforation, the median APACHE II score was 11. Median duration of VAC treatment was 12 days (range 3-88 days). Twenty of 43 (47 %) patients died from septic complications. Delayed fascial closure was obtained by suturing in 20 of 43 patients (47 %). Overall 16 of 43 (37 %) patients developed enteroatmospheric fistulas. Re-explorations after starting VAC treatment and duration of VAC therapy were significantly associated with the occurrence of enteroatmospheric fistulas (p < 0.001). ROC curve analysis determined the optimal duration of VAC therapy to reduce the risk of fistula formation at 13 days. CONCLUSIONS: Long-term VAC treatment of patients with an open abdomen due to secondary peritonitis results in a relatively low fascial closure rate and a high risk of fistula formation.

Efficacy and Safety Profile of Anti-tumor Necrosis Factor-α Versus Anti-integrin Agents for the Treatment of Crohn's Disease: A Network Meta-analysis of Indirect Comparisons.

PURPOSE: To compare the benefits and harms of anti-tumor necrosis factor (TNF)-α and anti-integrin agents as induction and maintenance therapy in adult patients with Crohn's disease. METHODS: We searched MEDLINE and the Cochrane Central Register of Controlled Trials from inception through July 2015 for randomized clinical trials in patients with Crohn's disease who reported response or remission with anti-TNF-α or anti-integrin agents administered as induction and/or maintenance therapy. Data on the study population, interventions, outcome measures, adverse events, and study methods were extracted independently by 2 authors. FINDINGS: Among 2503 citations identified, 23 met the eligibility criteria. Random-effects model meta-analyses and network meta-analyses were performed. No statistically significant difference was observed between anti-TNF-α and anti-integrin agents with respect to induction and maintenance of response (odds ratio [OR] = 1.20 [95% CI, 0.73-1.96] from 14 trials and OR = 1.23 [95% CI, 0.50-3.03] from 8 trials, respectively) or remission (OR = 1.13 [95% CI, 0.72-1.76] from 17 trials and OR = 1.18 [95% CI, 0.55-2.50] from 9 trials, respectively). No difference was observed in the indirect comparison of trials that reported results on the subgroup of anti-TNF-α naive patients. The proportions of patients with adverse events, infections, and treatment discontinuations were similar between the agents. IMPLICATIONS: Our indirect treatment comparisons did not find a statistically significant difference between anti-TNF-α and anti-integrin agents for induction or maintenance therapy. In the absence of head-to-head comparisons, it remains unclear which patient is more likely to respond better to any of these agents.

Assessing the relative effectiveness and tolerability of treatments in small cell lung cancer: a network meta-analysis.

BACKGROUND: The combination of Cisplatin plus Etoposide (EP) is currently the standard treatment for small cell lung cancer (SCLC). However, a large number of alternative treatments (monotherapies and combinations) have been studied in randomized controlled trials (RCTs) to identify more effective treatments. Aim of the present study was to assess the relative effectiveness and tolerability of these treatments. METHODS: PubMed, EMBASE and Cochrane Central Register of Controlled Trials were systematically searched to identify all RCTs that compared treatments for SCLC. Then, effectiveness of the treatments relative to the combination of Cisplatin plus Etoposide, reference treatment) was estimated by performing a network of treatments analysis. The analysis evaluated two efficacy outcomes (complete response - CR and objective response rate - ORR) and two tolerability outcomes (neutropenia and febrile neutropenia). All RCTs that provided data for calculating the odds ratios (OR) for the selected outcomes were considered. The network analysis involved direct and indirect analyses. RESULTS: We identified 71 articles eligible for inclusion, involving 91 different treatments. In total, 16,026 patients were included in the analysis. In the direct analysis the combination of Cisplatin plus Cyclophosphamide plus Etoposide plus Epirubicin showed better response than EP for the ORR outcome, but with worse tolerability (presence of neutropenia). The indirect analysis revealed that the combination of Cisplatin plus Doxorubicin plus Etoposide (plus Vincrisitine) showed better response that EP for the ORR outcome. CONCLUSIONS: No therapy shows better response for the two efficacy outcomes (CR and ORR); though, Cisplatin plus Doxorubicin plus Etoposide plus Vincrisitine might be a promising therapy for SCLC. The results should be interpreted with caution because the network was dominated by indirect comparisons. Large scale head-to-head RCTs are needed to confirm the present findings.