Analysis of the effect of staple line reinforcement on leaking and bleeding after sleeve gastrectomy from the UK National Bariatric Surgery Registry.

INTRODUCTION: Sleeve gastrectomy (SG) is currently the most frequently performed procedure for obesity worldwide. Staple line reinforcement (SLR) has been suggested as a strategy to reduce the risk of staple line leak or bleeding; however, its use for SG in the United Kingdom (UK) is unknown. This study examined the effect of SLR on the development of postoperative complications from SG using a large national dataset from the UK. METHODS: Patients undergoing either primary or revision SG over 10 years from Jan 2012 to Dec 2021 were identified by the National Bariatric Surgery Registry. Comparative and logistic regression analyses were undertaken to determine the effect of SLR on staple line leak and bleeding. RESULTS: During this time, 14,231 patients underwent SG for whom there were complete data. Of these, 76.5% were female and the median age was 46 years (IQR: 36-53). The rate of surgical complications was 2.3% (n = 219/14,231). The incidence of bleeding was 1.3% (n = 179/14,231) and leak was 1.0% (n = 140/14,231). Over time, the use of SLR of any variety declined significantly from 99.7% in 2012 to 57.3% in 2021 (p < 0.001). Multivariable (adjusted) regression analysis demonstrated that neither the use of nor the type of reinforcement had any effect on the rate of bleeding or leaking. CONCLUSION: SLR for SG has declined in the UK since 2012. There were no differences in staple line leak or bleed with or without reinforcement.

Efficacy of Nissen Sleeve Gastrectomy on Mid-term Barrett's Esophagus Regression.

INTRODUCTION: Sleeve gastrectomy is the most commonly performed bariatric operation globally. The main complication is GERD. In the medium term, it can increase the incidence of Barrett's esophagus (BE), which is a risk factor for esophageal adenocarcinoma. Following conventional sleeve gastrectomy, BE is noted in up to 16% of patients postoperatively. Recently, Nissen sleeve gastrectomy (NSG) has been shown to reduce the frequency of postoperative GERD compared to conventional sleeve gastrectomy. This study aims to evaluate the impact of NSG on the incidence and remission of BE in the long term. MATERIAL AND METHOD: This bicentric retrospective study included 692 patients who received NSG from September 2013 to July 2021. All patients underwent preoperative upper GI endoscopy and were then scheduled to receive upper GI endoscopy between 1 and 2 years and then between 3 and 5 years postoperatively. BE was systematically confirmed by biopsies. RESULTS: Seventy-four patients had endoscopic suspicion of BE, which was confirmed on 54/692 patients by histology. The BE lesions consisted of 18.5% intestinal metaplasia and 75.9% fundal metaplasia. Among these 54 patients, 38 underwent endoscopic investigation within 2 years postoperatively. The biopsies showed healed BE in 25/38 patients (64.1%). At 5 years, two patients had proven BE. Concerning the incidence of BE post NSG: 234 performed the follow-up endoscopy within 2 years. The incidence of de novo BE is nil. CONCLUSION: The NSG is associated with healing of known BE in approximately two-thirds of patients at 2-year follow-up. This is consistent with the GERD improvement that has been shown with NSG.

Prospective evaluation of transoral outlet reduction (TORe) after Roux-en-Y gastric bypass (RYGB) failure.

BACKGROUND AND AIMS: Weight regain after RYGB is multifactorial including dilatation of the gastro-jejunal anastomosis. Transoral outlet reduction (TORe) procedure is a minimally invasive alternative to surgical anastomotic revision. METHODS: We conducted a prospective, multicenter, simple blind, randomized study in patients with weight regain following RYGB, comparing the efficacy of conventional nutritional and behavioral management associated with a TORe procedure (TORe group) with conventional management alone and a Sham procedure (Sham group). The main objective of this study was to evaluate the percentage of excess weight loss (%EWL) at 12 months after endoscopy. RESULTS: From January 2015 to January 2019, 73 subjects were randomized in four French Bariatric centers. The final analysis involved 50 subjects, 25 in each group, 44 women, 6 men, with an average BMI of 40.6 kg/m2. At 12 months, the average %EWL was significantly higher in the TORe group than in the Sham group (13.5 ± 14.1 vs. - 0.77 ± 17.1; p = 0.002). Cohen's d was 0.91, indicating a large effect size of the procedure on the %EWL. There was no significant difference between groups concerning the improvement of obesity-related comorbidities (diabetes and dyslipidemia) and quality of life at 12 months. We report frequent adverse events in the TORe group (20% had adverse events related to the procedure). Three adverse events were serious, including two perforations of the gastro-jejunal anastomosis after TORe group that led to the premature termination of the study. CONCLUSIONS: After RYGBP failure linked to the dilatation of the gastro-jejunal anastomosis, TORe procedure with nutritional management results in significantly higher %EWL at 12 months compared to patients with nutritional management alone. As surgery, this minimally invasive endoscopic procedure can be associated with severe adverse events.

Skin-Microbiome Assembly in Preterm Infants during the First Three Weeks of Life and Impact of Topical Coconut Oil Application.

The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.

Bariatric surgery provision in response to the COVID-19 pandemic: retrospective cohort study of a national registry.

BACKGROUND: When surgery resumed following the outbreak of the COVID-19 pandemic, guidelines recommended the prioritization of patients with greater obesity-related co-morbidities and/or higher body mass index. OBJECTIVE: The aim of this study was to record the effect of the pandemic on total number, patient demographics, and perioperative outcomes of elective bariatric surgery patients in the United Kingdom. SETTING AND METHODS: The United Kingdom National Bariatric Surgical Registry was used to identify patients who underwent elective bariatric surgery during the pandemic (1 yr from April 1, 2020). Characteristics of this group were compared with those of a pre-pandemic cohort. Primary outcomes were case volume, case mix, and providers. National Health Service cases were analyzed for baseline health status and perioperative outcomes. Fisher exact, χ2, and Student t tests were used as appropriate. RESULTS: The total number of cases decreased to one third of pre-pandemic volume (8615 to 2930). The decrease in operating volume varied, with 36 hospitals (45%) experiencing a 75%-100% reduction. Cases performed in the National Health Service fell from 74% to 53% (P < .0001). There was no change in baseline body mass index (45.2 ± 8.3 kg/m2 from 45.5 ± 8.3 kg/m2; P = .23) or prevalence of type 2 diabetes (26% from 26%; P = .99). Length of stay (median 2 d) and surgical complication rate (1.4% from 2.0%; relative risk = .71; 95% CI .45-1.12; P = .13) were unchanged. CONCLUSIONS: In the context of a dramatic reduction in elective bariatric surgery due to the COVID-19 pandemic, patients with more severe co-morbidities were not prioritized for surgery. These findings should inform preparation for future crises.

Results of the ARROW survey of anti-reflux practice in the United Kingdom.

Gastro-esophageal reflux disease (GERD) is a common, significant health burden. United Kingdom guidance states that surgery should be considered for patients with a diagnosis of GERD not suitable for long-term acid suppression. There is no consensus on many aspects of patient pathways and optimal surgical technique, and an absence of information on how patients are currently selected for surgery. Further detail on the delivery of anti-reflux surgery (ARS) is required. A United Kingdom-wide survey was designed to gather surgeon opinion regarding pre-, peri- and post-operative practice of ARS. Responses were received from 155 surgeons at 57 institutions. Most agreed that endoscopy (99%), 24-hour pH monitoring (83%) and esophageal manometry (83%) were essential investigations prior to surgery. Of 57 units, 30 (53%) had access to a multidisciplinary team to discuss cases; case-loads were higher in those units (median 50 vs. 30, P < 0.024). The most popular form of fundoplication was a Nissen posterior 360° (75% of surgeons), followed by a posterior 270° Toupet (48%). Only seven surgeons stated they had no upper limit of body mass index prior to surgery. A total of 46% of respondents maintain a database of their practice and less than a fifth routinely record quality of life scores before (19%) or after (14%) surgery. While there are areas of consensus, a lack of evidence to support workup, intervention and outcome evaluation is reflected in the variability of practice. ARS patients are not receiving the same level of evidence-based care as other patient groups.

Clinical characteristics of patients undergoing primary bariatric surgery in the United Kingdom based on the National Bariatric Surgery Registry.

Baseline demographic characteristics and operations undertaken for patients having bariatric surgery in the United Kingdom are largely unknown. This study aimed to describe the profile of patients having primary bariatric surgery in the National Health Service (NHS) or by self-pay, and associated operations performed for both pathways. The National Bariatric Surgery Registry dataset for 5 years between January 2015 and December 2019 was used. 34 580 patients underwent primary bariatric surgery, of which 75.9% were NHS patients. Mean patient age and initial body mass index were significantly higher for NHS compared to self-pay patients (mean age 45.8 ± 11.3 [SD] vs. 43.0 ± 12.0 years and initial body mass index 48.0 ± 7.9 vs. 42.9 ± 7.3 kg/m2 , p < .001). NHS patients were more likely to have obesity-related complications compared to self-pay patients: prevalence of Type 2 diabetes mellitus 27.7% versus 8.3%, hypertension 37.1% versus 20.1%, obstructive sleep apnoea 27.4% versus 8.9%, severely impaired functional status 19.3% versus 13.9%, musculoskeletal pain 32.5% versus 20.1% and being on medication for depression 31.0% versus 25.9%, respectively (all p < .001). Gastric bypass was the most commonly performed primary NHS bariatric operation 57.2%, but sleeve gastrectomy predominated in self-pay patients 48.7% (both p < .001). In contrast to self-pay patients, NHS patients are receiving bariatric surgery only once they are older and at a much more advanced stage of obesity-related disease complications.

A Video-Based Review of Important Technical Concepts in the Nissen-Sleeve Gastrectomy.

PURPOSE: The development of gastroesophageal reflux disease (GERD) is a commonly encountered scenario after sleeve gastrectomy. A recently reported technical amendment to incorporate a Nissen fundoplication is discussed in this multimedia article focussing on optimising outcomes and reducing complications. MATERIALS AND METHODS: An intraoperative video has been edited to demonstrate the Nissen-Sleeve Gastrectomy and important technical considerations in its technical performance. RESULTS: Gastrolysis is performed proximally from 6 cm proximal to the pylorus. Routine full mediastinal mobilisation of the oesophagus (5 cm) is completed. Cruroplasty is routinely performed. A short Nissen fundoplication is completed calibrated on a 37 French bougie and then sleeve gastrectomy is performed. Our team's experience suggests that careful manipulation of the fundus and using reproducible measurements of the fundus are key to completing the fundoplication whilst minimising complications. A control test with mobilisation of the bougie through the wrap is recommended at the end of the procedure. CONCLUSION: The Nissen-Sleeve Gastrectomy, as presented in this video, is safe and has good short-term efficacy outcomes. Longer term and randomised studies are ongoing.

Bariatric-metabolic surgery for NHS patients with type 2 diabetes in the United Kingdom National Bariatric Surgery Registry.

AIM: Bariatric-metabolic surgery is approved by the National Institute of Health and Care Excellence (NICE) for people with severe obesity and type 2 diabetes (T2DM) (including class 1 obesity after 2014). This study analysed baseline characteristics, disease severity and operations undertaken in people with obesity and T2DM undergoing bariatric-metabolic surgery in the UK National Health Service (NHS) compared to those without T2DM. METHODS: Baseline characteristics, trends over time and operations undertaken were analysed for people undergoing primary bariatric-metabolic surgery in the NHS using the National Bariatric Surgical Registry (NBSR) for 11 years from 2009 to 2019. Clinical practice before and after the publication of the NICE guidance (2014) was examined. Multivariate logistic regression was used to determine associations with T2DM status and the procedure undertaken. RESULTS: 14,948/51,715 (28.9%) participants had T2DM, with 10,626 (71.1%) on oral hypoglycaemics, 4322 (28.9%) on insulin/other injectables, and with T2DM diagnosed 10+ years before surgery in 3876 (25.9%). Participants with T2DM, compared to those without T2DM, were associated with older age (p < 0.001), male sex (p < 0.001), poorer functional status (p < 0.001), dyslipidaemia (OR: 3.58 (CI: 3.39-3.79); p < 0.001), hypertension (OR: 2.32 (2.19-2.45); p < 0.001) and liver disease (OR: 1.73 (1.58-1.90); p < 0.001), but no difference in body mass index was noted. Fewer people receiving bariatric-metabolic surgery after 2015 had T2DM (p < 0.001), although a very small percentage increase of those with class I obesity and T2DM was noted. Gastric bypass was the commonest operation overall. T2DM status was associated with selection for gastric bypass compared to sleeve gastrectomy (p < 0.001). CONCLUSION: NHS bariatric-metabolic surgery is used for people with T2DM much later in the disease process when it is less effective. National guidance on bariatric-metabolic surgery and data from multiple RCTs have had little impact on clinical practice.

Network Meta-Analysis of Metabolic Surgery Procedures for the Treatment of Obesity and Diabetes.

BACKGROUND: Metabolic surgery is part of a well-established treatment intensification strategy for obesity and its related comorbidities including type 2 diabetes (T2DM). Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) and one-anastomosis gastric bypass (OAGB) are the most commonly performed metabolic surgeries worldwide, but comparative efficacy is uncertain. This study employed network meta-analysis to compare weight loss, T2DM remission and perioperative complications in adults between RYGB, SG and OAGB. METHODS: MEDLINE, EMBASE, trial registries were searched for randomised trials comparing RYGB, SG and OAGB. Study outcomes were excess weight loss (at 1, 2 and 3-5 years), trial-defined T2DM remission at any time point and perioperative complications. RESULTS: Twenty randomised controlled trials were included involving 1803 patients investigating the three metabolic surgical interventions. RYGB was the index for comparison. The excess weight loss (EWL) demonstrated minor differences at 1 and 2 years, but no differences between interventions at 3-5 years. T2DM remission was more likely to occur with either RYGB or OAGB when compared to SG. Perioperative complications were higher with RYGB when compared to either SG or OAGB. Two-way analysis of EWL and T2DM remission against the risk of perioperative complications demonstrated OAGB was the most positive on this assessment at all time points. CONCLUSION: OAGB offers comparable metabolic control through weight loss and T2DM remission to RYGB and SG whilst minimising perioperative complications. Registration number: CRD42020199779 (https:// www.crd.york.ac.uk/PROSPERO ).

Obstructive sleep apnea remission following bariatric surgery: a national registry cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) is strongly associated with metabolic syndrome. Bariatric surgery is an effective available treatment for OSA; however, limited research predicts which patients undergoing bariatric surgery will undergo OSA resolution. OBJECTIVES: To determine perioperative predictors for OSA resolution following bariatric surgery using a national database. SETTING: United Kingdom national bariatric surgery database. METHODS: The UK National Bariatric Surgery Registry (NBSR) was interrogated to identify all patients with OSA that underwent primary bariatric surgery between January 2009 and June 2017. Those with at least 1 follow-up recording postoperative OSA status were selected for further analysis. Demographic, pre- and postoperative outcomes were collected and analyzed. Poisson multivariate regression was conducted to identify predictors of OSA remission. RESULTS: A total of 4015 bariatric cases were eligible for inclusion: 2482 (61.8%) patients underwent laparoscopic Roux-en-Y gastric bypass (LRYGB), 1196 (29.8%) sleeve gastrectomy (LSG), and 337 (8.4%) adjustable gastric banding (LAGB). Overall, the mean excess weight loss (EWL) % for the whole group was 61.2 (SD ± 27.2). OSA resolution was recorded in 2377 (59.2%) patients. Following Poisson regression, LRYGB (risk ratio [RR], 1.49 confidence interval [CI] 1.25-1.78) and LSG (RR, 1.46 [CI 1.22-1.75] were associated with approximately 50% increased likelihood of OSA remission compared with LAGB. Greater weight loss following intervention was associated with greater likelihood of OSA remission, while both greater age and greater preoperative body mass index (BMI) were associated with reduced likelihood of OSA remission (P < .001). CONCLUSION: This study demonstrated that metabolic surgery results in OSA remission in the majority of patients with obesity. Younger age, lower BMI preprocedure, greater %EWL and the use of LSG or LRYGB positively predicted OSA remission.

Systematic Review and Meta-Analysis of the Impact of Bariatric Surgery on Lower Urinary Tract Symptoms in Males.

BACKGROUND: Obesity is a chronic disease with multisystem morbidity. There are multiple studies reporting the effect of bariatric surgery on cardiovascular and metabolic disease, but few examine its impact on lower urinary tract symptoms. This article aims to perform a systematic review with meta-analysis, to determine the effects of bariatric surgery on lower urinary tract symptoms in male patients. METHODS: Medline, Embase, conference proceedings, and reference lists were searched for studies reporting the quantitative measurement of lower urinary tract symptoms score pre- and postweight loss surgery. The primary outcome was International Prostate Symptom Score (IPSS) before and after bariatric surgery. Secondary outcomes were changed in body mass index (BMI) and total body weight (TBW). Weighted mean differences (MD) were calculated for continuous outcomes. RESULTS: Seven studies were included in the analysis of 334 patients undergoing bariatric surgery. Mean study follow-up was between 3 and 36 months. IPSS score ranged from 3-12.7 preoperatively and 1.9-6.9 postoperatively. There was a statistically significant improvement in the IPSS score following bariatric surgery (MD 2.82, 95% CI 0.96 to 4.69, p=0.003). Bariatric surgery also resulted in statistically significant reduction of BMI and TBW. CONCLUSION: Bariatric surgery produces a significant improvement on lower urinary tract symptoms in men with obesity. This may be due to improvement of insulin sensitivity, testosterone levels or lipid profile associated with weight loss.

Systematic Review of Innovation Reporting in Endoscopic Sleeve Gastroplasty.

BACKGROUND: Endoscopic sleeve gastroplasty (ESG) is a novel endoscopic procedure used to treat obesity-related comorbidities. Whilst its use is increasing in clinical practice, there is comparatively little understanding about how it has been evaluated. This study aimed to systematically summarize and appraise the reporting of ESG in the context of guidelines for evaluating innovative surgical devices and procedures. METHODS: Systematic searches were used to identify all published studies reporting ESG insertion. Data collected included patient selection, governance arrangements, proceduralist expertise, technique description and outcome reporting. RESULTS: Searches identified 2289 abstracts; 37 full-text papers were included (one prospective comparative cohort study, 16 retrospective cohort studies, 17 prospective cohort studies and three case reports). No randomized trials were identified. Eighteen studies were conducted prospectively. The number of patients in the included studies ranged from 1 to 1000. The lower BMI limit ranged from 27 to 35 kg/m2. Research approvals were reported in 26 studies. Two studies reported on the learning curve. All studies reported some aspect of technical implementation, but many variations were noted. Suturing device used and suture pattern were the most commonly reported aspects (32 studies). Follow-up ranged from 1 to 24 months, but was 12 months or less in 28 studies. Forty-eight different outcomes were reported across all studies. CONCLUSION: The literature on ESG has demonstrated some progression in reporting and analysis and the next stage of assessment should be a randomized controlled trial to demonstrate efficacy.

A multicenter prospective audit to investigate the current management of patients undergoing anti-reflux surgery in the UK: Audit & Review of Anti-Reflux Operations & Workup.

BACKGROUND: There are a variety of surgical and endoscopic interventions available to treat gastroesophageal reflux disease. There is, however, no consensus on which approach is best.The aim of this national audit is to describe the current variation in the UK clinical practice in relation to anti-reflux surgery (ARS) and to report adherence to available clinical guidelines. METHODS: This national audit will be conducted at centers across the UK using the secure online web platform ALEA. The study will comprise two parts: a registration questionnaire and a prospective multicenter audit of ARS. All participating centers will be required to complete the registration questionnaire comprising details regarding pre-, peri-, and post-operative care pathways and whether or not these are standardized within each center. Following this, a 12-month multicenter prospective audit will be undertaken to capture data including patient demographics, predominant symptoms, preoperative investigations, surgery indication, intraoperative details, and postoperative outcomes within the first 90 days.Local teams will retain access to their own data to facilitate local quality improvement. The full dataset will be reported at national and international scientific congresses and will contribute to peer-reviewed publications and national quality improvement initiatives. CONCLUSIONS: This study will identify and explore variation in the processes and outcomes following ARS within the UK using a collaborative cohort methodology. The results generated by this audit will facilitate local and national quality improvement initiatives and generate new possibilities for future research in anti-reflux interventions.

Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis.

BACKGROUND: Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS. METHODS: We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay. RESULTS: Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis-induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor-α) and the regulatory cytokine IL-10. CONCLUSIONS: Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.

Regional Variation in Unmet Need for Metabolic Surgery in England: a Retrospective, Multicohort Analysis.

Metabolic surgery provision is severely limited despite extensive supportive trial evidence. This study estimated the eligible population and the unmet need for metabolic surgery within English regions. Health Survey for England, National Diabetes Audit and population estimates were used to estimate the metabolic surgery eligible population by English region. Hospital Episode Statistics data was examined for metabolic surgery procedure volume by region (2013-2019). Regression analysis examined factors associated with metabolic surgery eligibility. 7.3% of the English population is potentially eligible for metabolic surgery; equivalent to 3.21 million people. Only 0.20% of the eligible English population receive metabolic surgery per year (regional variation 0.08-0.41%). The metabolic surgery eligible population was more likely to be female, older, have fewer educational qualifications and live in more deprived areas.

The impact of cytokine levels in young South African children with and without HIV-associated acute lower respiratory infections.

Altered host immune responses are considered to play a key role in the pathogenesis of acute lower respiratory infections (ALRI). The existing literature on cytokine responses in ALRI is largely focussed on adults from developed countries and there are few reports describing the role of cytokines in childhood ALRI, particularly in African or human immunodeficiency virus (HIV)-infected populations. To measure systemic cytokine levels in blood plasma from young South African children with and without ALRI and with and without HIV to determine associations between cytokine responses and disease status and respiratory viral identification. Blood plasma samples were collected from 106 hospitalized ALRI cases and 54 non-ALRI controls less than 2 years of age. HIV status was determined. Blood plasma concentrations of 19 cytokines, 7 chemokines, and 4 growth factors (epidermal growth factor, fibroblast growth factor-basic, hepatocyte growth factor, and vascular endothelial) were measured using The Human Cytokine 30-Plex Panel. Common respiratory viruses were identified by PCR. Mean cytokine concentrations for G-CSF, interferon (IFN)-γ, interleukin (IL)-5, and MCP-1 were significantly higher in ALRI cases than in nonrespiratory controls. Within the ALRI cases, several cytokines were higher in children with a virus compared with children without a virus. Mean cytokine concentrations for IFN-α, IFN-γ, IL-4, IL-5, IL-13, tumour necrosis factor-α, and MIP-1α were significantly lower in HIV-infected cases than in HIV-uninfected cases, while IP-10 and monokine induced by interferon-γ were significantly higher in HIV-infected cases than in HIV-uninfected cases. Certain cytokines are likely to play an important role in the host immune response to ALRI. HIV-infected children have impaired inflammatory responses to respiratory infections compared with HIV-uninfected children.

A Meta-analysis of the Impact of Bariatric Surgery on Back Pain.

BACKGROUND: The functional aspects of obesity are increasingly recognised as a significant clinical and public health concern. Whilst there is substantial evidence for the beneficial impact of bariatric surgery on metabolic and cardiovascular disease, there is less understanding of the quantitative effect of bariatric surgery on back pain. The aim of this meta-analysis was to assess the impact of bariatric surgery on back pain in reported studies. METHODS: Medline, Embase, conference proceedings and reference lists were searched for studies assessing quantitative back pain scores both before and after bariatric surgery. The primary outcome was visual analogue score for back pain pre- and post-bariatric surgery. Secondary outcomes were change in BMI, SF-36 quality of life scores and Oswestry Disability Index (ODI) scores. Weighted mean differences (MD) were calculated for continuous outcomes. RESULTS: Seven studies were included in the analysis of 246 patients undergoing bariatric surgery. Mean study follow-up was between 3 and 24 months. There was a statistically significant reduction in visual analogue score for back pain following bariatric surgery (MD - 3.01; 95% CI - 4.19 to - 1.89; p < 0.001). Bariatric surgery also resulted in statistically significant improvements in BMI, SF-36 score and ODI score. CONCLUSIONS: Bariatric surgery produces significant and quantifiable reductions in back pain. This may be commuted through reductions in axial load or improved quality of life, but further studies will improve understanding and aid preoperative counselling.

Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.

BACKGROUND: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life. METHODS: Cord and serial peripheral blood samples (days of life 1-28) were obtained from a cohort of very preterm (<30 weeks' gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay. RESULTS: cAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1ß, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis. CONCLUSIONS: The ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.

Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy.

Immunization of patients with autologous, ex vivo matured dendritic cell (DC) preparations, in order to prime antitumor T-cell responses, is the focus of intense research. Despite progress and approval of clinical approaches, significant enhancement of these personalized immunotherapies is urgently needed to improve efficacy. We show that immunotherapeutic murine and human DC, generated in the presence of the antimicrobial host defense peptide LL-37, have dramatically enhanced expansion and differentiation of cells with key features of the critical CD103+/CD141+ DC subsets, including enhanced cross-presentation and co-stimulatory capacity, and upregulation of CCR7 with improved migratory capacity. These LL-37-DC enhanced proliferation, activation and cytokine production by CD8+ (but not CD4+) T cells in vitro and in vivo. Critically, tumor antigen-presenting LL-37-DC increased migration of primed, activated CD8+ T cells into established squamous cell carcinomas in mice, and resulted in tumor regression. This advance therefore has the potential to dramatically enhance DC immunotherapy protocols.