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BackgroundCurrent enhanced recovery guidelines suggest that opioid sparing medications should be used for analgesia whenever possible following colorectal surgery. The present study aims to assess whether post-operative NSAID use is associated with an increased anastomotic leak rate after a colonic or rectal anastomosis.MethodsA systematic review was performed for studies investigating anastomotic leak rate following NSAID use vs control after colonic or rectal anastomosis. Meta-analysis was performed to assess for overall risk of anastomotic leak with NSAID use, as well as sub-group analysis to compare selective vs non-selective NSAIDs and drug-specific NSAID safety profiles.ResultsSeven studies were included in the final review. Use of an NSAID post-operatively was associated with an overall increased risk of anastomotic leakage [OR 1.58 (1.23, 2.03), P = 0.0003]. Non-selective NSAIDs were associated with an increased risk [OR 1.79 (1.47, 2.18), P < 0.00001], but selective NSAIDs were not. The non-selective NSAID diclofenac was associated with an increased leak rate [OR 2.79 (1.96, 3.96), P < 0.00001], but ketorolac was not [OR 1.36 (0.89, 2.06), P = 0.16].ConclusionsGreat caution must be taken when prescribing NSAIDs following colonic or rectal anastomotic creation. The safety profile varies within the NSAID class and further research is needed to clarify which NSAIDs are safe for use and which are not.

Among surgical residents, research is often perceived as a check-mark exercise. Focus then turns to studying for exams and honing skills for independent practice. While some residents are passionate about research and enroll in other formalized training, pragmatists argue that not every surgeon should engage in research at this level. However, no resident should view research as a one-and-done activity. Rather, research should be viewed as an exercise to improve practice, share gaps in knowledge, collaborate, and empower others to formally study and implement change. The skills acquired during research experiences, at minimum, have value in improving the trainee’s literature literacy, which in turn serves as a foundational element of continuing medical education. A culture supportive of scientific discovery, facilitated by both faculty and peer-to-peer mentorship, will result in better collaborative efforts and lead to improved knowledge generation and resident research satisfaction.

Background Colonoscopy exposes endoscopists to awkward postures and prolonged forces, which increases their risk of musculoskeletal injury. Patient positioning has a significant impact on the ergonomics of colonoscopy. Recent trials have found the right lateral decubitus position is associated with quicker insertion, higher adenoma detection rates, and greater patient comfort compared to the left lateral decubitus position. However, this patient position is perceived as more strenuous by endoscopists. Methods Nineteen endoscopists were observed performing colonoscopies during a series of four-hour endoscopy clinics. Durations of each patient position (right lateral decubitus, left lateral decubitus, prone, and supine) were recorded for all observed procedures ( n  = 64). Endoscopist injury risk was estimated by a trained researcher for the first and last colonoscopies of the shifts ( n  = 34) using Rapid Upper Limb Assessment (RULA), an observational ergonomic tool that estimates risk of musculoskeletal injury by scoring postures of the upper body and factors such as muscle use, force, and load. The total RULA scores were compared with a Wilcoxon Signed-Rank test for patient position (right and left lateral decubitus) and time (first and last procedures) with significance taken at p  < 0.05. Endoscopist preferences were also surveyed. Results The right lateral decubitus position was associated with significantly higher RULA scores than the left lateral decubitus position (median 5 vs. 3, p  < 0.001). RULA scores were not significantly different between the first and last procedures of the shifts (median 5 vs. 5, p  = 0.816). 89% of endoscopists preferred the left lateral decubitus position, primarily due to superior ergonomics and comfort. Conclusion RULA scores indicate an increased risk of musculoskeletal injury in both patient positions, with greater risk in the right lateral decubitus position.

ObjectiveTo investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.DesignPhase 3b multicentre, double-blind, randomised placebo-controlled trial.SettingTwenty-one hospitals in the UK.ParticipantsChildren aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308.InterventionTwo doses (1 g/kg/dose) of either IVIG or matching placebo given 24–36 hours apart, in addition to standard treatment.Main outcome measureThe primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended.Secondary outcome measuresThe secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data.Results18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG.ConclusionsThe IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis.Trial registration numberClinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.

Hermansky Pudlak type 2 syndrome (HPS2) is a rare autosomal recessive primary immune deficiency caused by mutations on β3A gene (AP3B1 gene). The defect results in the impairment of the adaptor protein 3 (AP-3) complex, responsible for protein sorting to secretory lysosomes leading to oculo-cutaneous albinism, bleeding disorders and immunodeficiency. We have studied peripheral blood and lymph node biopsies from two siblings affected by HPS2. Lymph node histology showed a nodular lymphocyte predominance type Hodgkin lymphoma (NLPHL) in both HPS2 siblings. By immunohistochemistry, CD8 T-cells from HPS2 NLPHL contained an increased amount of perforin (Prf) + suggesting a defect in the release of this granules-associated protein. By analyzing peripheral blood immune cells we found a significant reduction of circulating NKT cells and of CD56(bright)CD16(-) Natural Killer (NK) cells subset. Functionally, NK cells were defective in their cytotoxic activity against tumor cell lines including Hodgkin Lymphoma as well as in IFN-γ production. This defect was associated with increased baseline level of CD107a and CD63 at the surface level of unstimulated and IL-2-activated NK cells. In summary, these results suggest that a combined and profound defect of innate and adaptive effector cells might explain the susceptibility to infections and lymphoma in these HPS2 patients.

Key Clinical Message TNPM is a benign, transient, neonatal pustulosis requiring no active treatment. Diagnosis is clinical, characterized by a vesiculopustular eruption, healing with residual hyperpigmented macules. Before diagnosing TNPM, serious conditions including skin infections should be excluded. This case was unusual in that vesiculobullae predominated, with a notable absence of simple pustules. Flacid bullae and desquamation over the scalp and back of a 1 hour old neonate.

MenACWY-TT (Nimenrix ® ) is a quadrivalent meningococcal tetanus toxoid conjugate vaccine licensed in Europe for active immunisation of individuals aged ≥ 6 weeks against invasive disease caused by Neisseria meningitidis capsular groups A, C, W and Y. MenACWY-TT is the first quadrivalent conjugate vaccine to be approved in Europe for use in infants as young as 6 weeks of age. Numerous phase II–IIIb clinical studies showed that intramuscular MenACWY-TT administered as primary or booster vaccination was highly immunogenic for all four vaccine capsular groups and had an acceptable reactogenicity profile in individuals aged 6 weeks to ≥ 56 years. MenACWY-TT is as immunogenic and safe as other previously licensed monovalent capsular group C or quadrivalent capsular groups A, C, W and Y meningococcal vaccines and can be coadministered with other routine vaccines without adversely affecting the immunogenicity or safety profiles of either vaccine. Current data indicate that primary and booster vaccination with MenACWY-TT is a valuable and safe option for broadening meningococcal protection against four capsular groups across a broad age range, starting as early as 6 weeks of age.