Leveraging big data of immune checkpoint blockade response identifies novel potential targets.

BACKGROUND: The development of immune checkpoint blockade (ICB) has changed the way we treat various cancers. While ICB produces durable survival benefits in a number of malignancies, a large proportion of treated patients do not derive clinical benefit. Recent clinical profiling studies have shed light on molecular features and mechanisms that modulate response to ICB. Nevertheless, none of these identified molecular features were investigated in large enough cohorts to be of clinical value. MATERIALS AND METHODS: Literature review was carried out to identify relevant studies including clinical dataset of patients treated with ICB [anti-programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the combination] and available sequencing data. Tumor mutational burden (TMB) and 37 previously reported gene expression (GE) signatures were computed with respect to the original publication. Biomarker association with ICB response (IR) and survival (progression-free survival/overall survival) was investigated separately within each study and combined together for meta-analysis. RESULTS: We carried out a comparative meta-analysis of genomic and transcriptomic biomarkers of IRs in over 3600 patients across 12 tumor types and implemented an open-source web application (predictIO.ca) for exploration. TMB and 21/37 gene signatures were predictive of IRs across tumor types. We next developed a de novo GE signature (PredictIO) from our pan-cancer analysis and demonstrated its superior predictive value over other biomarkers. To identify novel targets, we computed the T-cell dysfunction score for each gene within PredictIO and their ability to predict dual PD-1/CTLA-4 blockade in mice. Two genes, F2RL1 (encoding protease-activated receptor-2) and RBFOX2 (encoding RNA-binding motif protein 9), were concurrently associated with worse ICB clinical outcomes, T-cell dysfunction in ICB-naive patients and resistance to dual PD-1/CTLA-4 blockade in preclinical models. CONCLUSION: Our study highlights the potential of large-scale meta-analyses in identifying novel biomarkers and potential therapeutic targets for cancer immunotherapy.

Effect of CPAP treatment on BP in resistant hypertensive patients according to the BP dipping pattern and the presence of nocturnal hypertension.

High heterogeneity in the blood pressure (BP) response to continuous positive airway pressure (CPAP) exists in patients with resistant hypertension (RH). Only nondipper normotensive and hypertensive patients exhibited BP reductions when treated with CPAP; the baseline BP dipping pattern has been proposed as a predictor of BP response to CPAP but has never been explored in patients with RH. This study aimed to assess the effect of CPAP on BP in subjects with RH with respect to BP dipping pattern or nocturnal hypertension. This is an ancillary study of the SARAH study. RH subjects with an apnea/hypopnea index (AHI) ≥ 15/h and who received CPAP treatment for 1 year were included. Subjects underwent a sleep study and ambulatory BP monitoring (ABPM) at baseline and at the 1-year follow-up. Eighty-nine RH subjects were included. The subjects were mainly male (77.5%) and obese, with a mean age of 66 years (25th-75th percentile; 59.0; 70.0) and an AHI of 32.7/h (25th-75th percentile; 25.0; 54.7). A total of 68.5% of participants were nondippers, and 71.9% had nocturnal hypertension. After 1 year of CPAP, no significant differences in ABPM parameters were observed between dippers and nondippers. According to nighttime BP, subjects with nocturnal normotension did not show significant changes in ABPM parameters, while nocturnal hypertensive subjects achieved a significant reduction in mean nighttime BP of -4.38 mmHg (-7.10 to -1.66). The adjusted difference between groups was 3.04 (-2.25 to 8.34), which was not significant. This study shows that the BP response to CPAP in patients with RH does not differ according to the BP dipping pattern (dipper and nondipper) and suggests a differential response according to the presence of nocturnal hypertension (ClinicalTrials.gov: NCT03002558).

Analgesic effects of a 5-HT3 receptor antagonist in an animal model of complex regional pain syndrome.

OBJECTIVE: Complex regional pain syndrome (CRPS) is caused by injuries from fracture after trauma and orthopaedic surgical procedures in the hind limbs. The symptoms of CRPS include warmth, pain, allodynia, and hyperalgesia. It is known that 5-hydroxytryptamine 3 (5-HT3) receptors contribute to hyperalgesia, but their role has not yet been fully elucidated. This study investigated the mechanism of pain relief when a 5-HT3 receptor antagonist was administered in a CRPS animal model. MATERIALS AND METHODS: To establish a CRPS animal model, 10-week-old Sprague-Dawley rats were used in the experiment. On the fourth week post tibial fracture surgery, we performed the von Frey test to measure mechanical allodynia. After performing behavioural tests, we collected blood and tissue samples after sacrificing the animals. Enzyme-linked immunosorbent assay and western blot were also performed. RESULTS: The experimental tibia fracture model-induced CRPS animals elicited increased 5-HT3 receptor expression, and the 5-HT transporter was decreased in the brain stem after 4 weeks of surgical intervention. Additionally, in CRPS-induced animals, both the concentration of substance P and the level of interleukin 6 were increased peripherally and centrally. Treatment with the 5-HT3 receptor antagonist, ramosetron, exerted an analgesic effect in the paw withdrawal test and was dependent on the attenuation of the 5-HT3 receptor population with inflammatory pain mediators. CONCLUSIONS: These data suggest that treatment with the 5-HT3 receptor antagonist, ramosetron, in experimental CRPS animal models alleviated pain-related behaviours and may be a new therapeutic option or potential therapeutic agent for patients with CRPS.

Mucin 5AC is significantly upregulated in exosomes from the nasal lavage fluid and may promote the expression of COX-2, VEGF and MMP-9: an implication in nasal polyp pathogenesis.

BACKGROUND: Exosomes are critical mediators of intercellular communication and could be involved in many human diseases; however, little is known about the role of exosomes in nasal polyps (NP). METHODS: Exosomes in nasal lavage fluids (NLF) were isolated by ultracentrifugation. Exosome identity was validated by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and specific exosomal markers. The exosome proteome was revealed by LC-MS/MS, and the expression of the candidate exosomal protein, mucin 5AC, was confirmed by Western blot analysis and immunohistochemistry (IHC). Cellular uptake of the exosomes was monitored by fluorescence confocal microscopy and the ensuing effects on COX-2, VEGF and MMP-2/MMP-9 were determined by Western blotting, ELISA and gelatin zymography, respectively. RESULTS: Mass spectrometry analysis and subsequent verification by Western blotting identified that mucin 5AC was significantly upregulated in exosomes from NLFs of NP patients. Moreover, the expression of mucin 5AC was increased in the tissue specimens of the NP patients. Functional assays suggest that the mucin 5 AC-enriched exosomes could be effectively taken up by chronic rhinosinusitis without NP (CRSsNP)-derived fibroblasts, the control cells, resulting in a significant increase in the expression of COX-2, VEGF and MMP-9. CONCLUSIONS: Mucin 5AC, the major airway mucin, cannot only be carried and transferred by nasal exosomes, but may also promote tissue remodeling and angiogenesis and thus could be a potential therapeutic target of NP.

Energy calibration of charged particle detectors using discrete and continuous energy spectra of 137Cs.

An improved method for energy calibration of particle detectors is presented utilizing both the discrete and continuous spectra from the conversion electrons and beta particles of a radioisotope of  137Cs. This method considers the instrument response against the discrete spectrum from the conversion electrons at 624.22 keV and the continuous spectrum from the beta particles emitted by the unique first forbidden transition in the energy range of approximately 120-513 keV. The instrument response is determined by fitting model functions to the measurements, from which the energy scale and energy resolution of the instrument are derived. Inclusion of the beta particles in this method enables a determination of the energy scale in a broader energy range as well as the DC-offset and non-linearity of the instrument. This is an improvement from the conventional method that only utilizes a mono-energetic peak from the conversion electrons. A detailed description of the procedure is provided, from constructing the model functions to determining the instrument response. Results of the method, as successfully applied to a space-borne instrument, are provided to demonstrate the method.

A matching-adjusted indirect comparison of combination nivolumab plus ipilimumab with BRAF plus MEK inhibitors for the treatment of BRAF-mutant advanced melanoma☆.

BACKGROUND: Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC). PATIENTS AND METHODS: A systematic literature review identified RCTs for DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma. Individual patient-level data for NIVO+IPI were derived from the phase III CheckMate 067 trial (BRAF-mutant cohort) and restricted to match the inclusion/exclusion criteria of the comparator trials. Treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using Cox proportional hazards and time-varying hazard ratio (HR) models. Safety outcomes (grade 3 or 4 treatment-related adverse events) with NIVO+IPI and the comparators were compared. RESULTS: In the Cox proportional hazards analysis, NIVO+IPI showed improved OS compared with DAB+TRAM (HR = 0.53; 95% confidence interval [CI], 0.39-0.73), ENCO+BINI (HR = 0.60; CI, 0.42-0.85), and VEM+COBI (HR = 0.50; CI, 0.36-0.70) for the overall study period. In the time-varying analysis, NIVO+IPI was associated with significant improvements in OS and PFS compared with the BRAF/MEK inhibitors 12 months after treatment initiation. There were no significant differences between NIVO+IPI and BRAF/MEK inhibitor treatment from 0 to 12 months. Safety outcomes favored DAB+TRAM over NIVO+IPI, whereas NIVO+IPI was comparable to VEM+COBI. CONCLUSION: Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.

Phase Angle and Frailty Are Important Prognostic Factors in Critically Ill Medical Patients: A Prospective Cohort Study.

OBJECTIVES: To investigate whether phase angle (PhA) measured by bioelectrical impedance analysis (BIA) and frailty are associated with the outcomes of critical illnesses. DESIGN: A single-center prospective cohort study. SETTING: Medical intensive care unit (ICU) in Seoul National University Hospital, Seoul, Republic of Korea. PARTICIPANTS: 97 patients who were admitted to the medical ICU. MEASUREMENTS: On admission, PhA was measured by BIA, and frailty was assessed by the Korean Modified Barthel Index (KMBI) scoring system. Patients were classified according to PhA and KMBI scores, and their impact on the outcomes of critical illnesses was evaluated. RESULTS: The patients' mean age was 62.4 ± 16.4 years, and 56 of the patients (57.7%) were men. Having a high PhA above 3.5 at the time of ICU admission was associated with lower in-hospital mortality (adjusted OR 0.42, p = .042), and a shorter duration of ICU stay (5.6 days vs. 9.8 days, p = .016) compared to those with a low PhA. Other indices measured by BIA were not significantly associated with outcomes of critical illnesses. Frailty (KMBI > 60) was associated with more mechanical ventilation days (2.3 days vs. 7.1 days; p = .018). CONCLUSION: Both PhA and frailty are important prognostic factors predicting the outcomes of critical illnesses. Low PhA scores were associated with increased mortality and a longer duration of ICU stay, and frailty was associated with more mechanical ventilation days.

Knowledge, attitudes and practices of neonatal professionals regarding pain management.

Pain management is an important issue which impacts the prognosis of neonates in neonatal intensive care units. Evidence has shown that professionals' knowledge and attitudes regarding pain management can impact the quality of their practice. The purpose of this study was to evaluate the knowledge, attitudes, and practices of neonatal professionals regarding neonatal pain management. A cross-sectional study was performed involving neonatal physicians and nurses, using a research questionnaire to investigate the knowledge and attitudes of professionals as well as to assess their practice of pain management. Research found an apparent discrepancy between the knowledge levels of neonatologists and nurses regarding pain assessment and management, with nurses displaying weaker professional knowledge and more negative attitudes toward pain management than did neonatologists. Additionally, research revealed a lack of knowledge and negative attitudes among participants regarding the provision of sufficient opioid analgesics to sick infants during invasive procedures and even for dying neonates. There is an urgent need for continuing education regarding neonatal pain management with the goal of empowering neonatal professionals; further research is needed into the question of how to translate education into more reliable practice.Conclusion: This research provides useful information regarding the knowledge, attitudes, and clinical practice of neonatal pain management among neonatologists and nurses and points out some differences in the knowledge levels of these two groups. What is Known: •Neonates can perceive and respond to pain stimuli by showing their biological signals similarly to children and adults. •Untreated or insufficient pain management for high-risk neonates has short-term. negative effects and may also induce long-term negative effects. What is New: •The level of knowledge, the attitudes, and the practices regarding neonatal pain in intensive care are different among neonatal professionals. •There is an urgent need to provide interdisciplinary continuing education to improve the knowledge of neonatal professionals and encourage them to more highly prioritize neonatal pain management.

Transition Strength Measurements to Guide Magic Wavelength Selection in Optically Trapped Molecules.

Optical trapping of molecules with long coherence times is crucial for many protocols in quantum information and metrology. However, the factors that limit the lifetimes of the trapped molecules remain elusive and require improved understanding of the underlying molecular structure. Here we show that measurements of vibronic line strengths in weakly and deeply bound ^{88}Sr_{2} molecules, combined with ab initio calculations, allow for unambiguous identification of vibrational quantum numbers. This, in turn, enables the construction of refined excited potential energy curves, informing the selection of magic wavelengths that facilitate long vibrational coherence. We demonstrate Rabi oscillations between far-separated vibrational states that persist for nearly 100 ms.

Benign postoperative hepaticojejunostomy stricture: percutaneous recanalisation using the reverse end of a microwire.

AIM: To evaluate the technical feasibility and safety of percutaneous recanalisation of benign postoperative hepaticojejunostomy strictures using the reverse end of a microwire. MATERIALS AND METHODS: Twenty-one patients with benign postoperative hepaticojejunostomy strictures that had failed to recanalise following management with conventional percutaneous techniques from January 2012 to March 2019 were included in the study. The stricture was punctured by the reverse end of a microwire. Subsequently, serial balloon dilatation and covered stent placement was performed. Technical as well as clinical success, complications, and patency of the hepaticojejunostomy were evaluated. RESULTS: Technical success was achieved in 19 of 21 (90.5%) patients. The mean number of treatment sessions was 1.2 (range, 1-2). The obstructive symptoms were resolved within 3 days after the procedure in 19 patients (100%). There were no major complications. The 1-year and 3-year patency rates were 76.9% and 61.5%, respectively. CONCLUSION: Percutaneous recanalisation using the reverse end of a microwire is technically feasible and safe in the treatment of benign postoperative hepaticojejunostomy strictures. This technique is useful when the conventional percutaneous technique cannot be used to cross the stricture.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

Effects of quorum quenching on temporal succession of activated sludge microbial community in a membrane bioreactor.

AIMS: Quorum quenching (QQ) is an attractive strategy for mitigating biofouling in membrane bioreactors (MBRs). However, the effects of QQ on the activated sludge (AS) process have not been adequately evaluated. This study investigated the long-term effects of QQ on a laboratory-scale anoxic-oxic MBR, focusing on AS performance and microbial community. METHODS AND RESULTS: Anoxic-oxic MBRs with and without QQ were operated for 91 days. QQ did not affect COD and TN removal efficiencies over the experimental period, during which its activity remained >90%. QQ reduced floc size by approximately 8% but had no effect on biomass concentration. AS microbial communities were regularly analysed using massively parallel sequencing. AS bacterial communities were temporally dynamic irrespective of QQ presence, for example, a temporal increase in bacterial diversity and a temporal decay of community similarity. QQ counteracted the temporal change in diversity and the temporal distance-community decay. Community comparison revealed that QQ changed the successional trajectory of the AS community at a late period, because it decelerated temporal changes of specific members, such as Thiothrix and Sphingomonadaceae*. Correlation networks revealed that QQ increased network clustering, complexity and density. The combined results suggest that the tighter microbial association by QQ increased the community resistance. CONCLUSIONS: QQ can enhance the diversity and stability of the AS community in MBR by counteracting the innate temporal change in community structure. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings are useful for the further advancement of QQ-based strategies in engineered microbial environments.

Magnon profile on SrRuO3 films studied by inelastic neutron scattering.

In this study, the inelastic neutron scattering probe of SIKA in ANSTO is employed to investigate the magnon dispersion curve in ferromagnetic SrRuO3 single crystal epitaxial films and to better understand the underlying mechanisms. This report presents the successful measurement of a magnon peak from the SrRuO3 films which contained an amount of material of only 0.9 mg. We reveal one significant magnon dispersion curve along [002] following the quadratic E ∝ Q 2 ) relation, which shows a magnon gap of 0.32 meV. We have discussed several possible mechanisms, such as the higher symmetry structure and the impurity levels, which may contribute to this smaller gap.

Fine-tuning the photosynthetic light harvesting apparatus for improved photosynthetic efficiency and biomass yield.

Photosynthetic electron transport rates in higher plants and green algae are light-saturated at approximately one quarter of full sunlight intensity. This is due to the large optical cross section of plant light harvesting antenna complexes which capture photons at a rate nearly 10-fold faster than the rate-limiting step in electron transport. As a result, 75% of the light captured at full sunlight intensities is reradiated as heat or fluorescence. Previously, it has been demonstrated that reductions in the optical cross-section of the light-harvesting antenna can lead to substantial improvements in algal photosynthetic rates and biomass yield. By surveying a range of light harvesting antenna sizes achieved by reduction in chlorophyll b levels, we have determined that there is an optimal light-harvesting antenna size that results in the greatest whole plant photosynthetic performance. We also uncover a sharp transition point where further reductions or increases in antenna size reduce photosynthetic efficiency, tolerance to light stress, and impact thylakoid membrane architecture. Plants with optimized antenna sizes are shown to perform well not only in controlled greenhouse conditions, but also in the field achieving a 40% increase in biomass yield.

Revision adenoidectomy in children: a meta-analysis.

BACKGROUND: To estimate the rate of revision surgery after previous adenoidectomy in children and to compare the rate of revision adenoidectomy in children with different conditions and by using different surgical techniques. METHODOLOGY: The study protocol was registered on PROSPERO (CRD42018107877). Two authors independently searched databases, specifically PubMed, MEDLINE, EMBASE, and the Cochrane Review database. The keywords used were "adenoids","adenoidectomy","reoperation","revision"and "regrowth". The revision rate was pooled using a random-effect model. Subgroup analyses were conducted for children based on different settings, countries, risks of bias, and surgical techniques. RESULTS: A total 16 studies with 95 727 children were analyzed (mean age: 4.69 (1.62) years; 60% boys; sample size: 5983 patients). Five studies had a low risk of bias, 10 studies had a moderate risk of bias, and one study had a high risk of bias. The rate of revision adenoidectomy was 1.9%. Ages at initial surgery and follow-up were not significantly associated with revision surgeries. The revision rate was not significantly different in children receiving surgeries in different settings (single center vs multicenter vs population-based, country (non-United States vs United States, and risk of bias. Moreover, surgical techniques, such as curettage, suction cautery, microdebridement, and coblation did not significantly affect revision rates in children who received adenoidectomy. CONCLUSIONS: Revision surgery was undertaken with a frequency of 1.9% in children who underwent adenoidectomy. A lack of strong evidence exists to correlate surgical techniques with revision rate in pediatric adenoidectomy.

Effect of chlorhexidine bathing on colonization or infection with Acinetobacter baumannii: a systematic review and meta-analysis.

Healthcare-associated infections (HAIs) caused by multi-drug-resistant Gram-negative bacteria (MDRGNB) have increased prevalence in intensive care units (ICUs). A common strategy to prevent HAIs is bathing patients with chlorhexidine gluconate (CHG). However, the effectiveness of CHG bathing against multidrug-resistant Acinetobacter baumannii (MDRAB) is still controversial. The aim of this study was to perform a systematic review and meta-analysis of the effectiveness of CHG bathing on Acinetobacter baumannii colonization and infection in the ICU setting. A systematic literature search of PubMed, EMBASE, Web of Science and CINAHL was performed from inception through to June 2018. Randomized controlled trials (RCTs), pre-post studies, or interrupted time series (ITS) studies were included. The numbers of patients with/without colonization or infection of A. baumannii in the experimental or control groups were extracted from each study. Quality assessment was performed by the related instruments of National Institute of Health. Pooled risk ratios (RRs) were calculated using the random-effects model. One RCT and 12 pre-post or ITS studies comprising 18,217 patients were included, of which 8069 were in the CHG bathing arm and 9051 in the control arm. CHG bathing was associated with a reduced colonization of A. baumannii (RR, 0.66; 95% confidence interval: 0.57-0.77; P<0.001). Chlorhexidine at 4% showed a better effect than 2% chlorhexidine (meta-regression P=0.044). CHG bathing was associated with a non-significant reduction of infection (pooled RR 0.41, 95% CI: 0.13-1.25). This study suggests that CHG bathing significantly reduces colonization of A. baumannii in the ICU setting. However, more trials are needed to confirm whether CHG bathing can reduce infections with A. baumannii.

Wound Closure after Thyroid and Parathyroid Surgery: A Meta-Analysis of Randomized Controlled Trials.

AIMS: Wound closure after thyroidectomy and parathyroidectomy is associated with patients' satisfaction, perception of cosmetic appearance, and experience of postoperative pain. Subcutaneous sutures, clips, and tissue adhesive are the three major methods of wound closure. In this study, we conducted a meta-analysis of randomized controlled trials to evaluate the outcomes of these methods. METHODS: Relevant studies published before December 2017 were identified from PubMed, Embase, Cochrane Library, Scopus, and the ClinicalTrials.gov registry. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using random-effect models. The primary outcome was the cosmetic appearance, which was evaluated 4 weeks, 6 weeks, and 6 months after surgery. The secondary outcomes were patient satisfaction, postoperative pain, and complications. RESULTS: A total of nine trials with 612 patients were reviewed. No significant difference was observed in patient satisfaction, postoperative pain, and complications among the wound closure methods. However, according to surgeon assessment, the subcutaneous suture method resulted in a significantly more favorable cosmetic appearance than the clip method (mean difference: -1.47, 95% confidence interval: -2.72 to -0.23). CONCLUSION: In the current study, no differences were found in patient satisfaction and postoperative pain among the subcutaneous suture, clip, and tissue adhesive wound closure methods. However, surgeons provided a more favorable appraisal for the subcutaneous suture method because of the improved cosmetic appearance. The choice of the closure method should be based on surgeon's preference and cost.

Clopidogrel may decrease the risk of post-stroke infection after ischaemic stroke.

BACKGROUND AND PURPOSE: The P2Y12 receptor, a well-known factor in the platelet activation pathway, plays a role in thrombosis as well as systemic inflammation. Clopidogrel, a prototype P2Y12 receptor antagonist, reportedly decreases inflammation and systemic infection. The aim of this study was to evaluate whether clopidogrel use decreases the risk of post-stroke infection following ischaemic stroke. METHODS: A total of 1643 patients with acute ischaemic stroke (within 7 days after onset) were included for analysis between March 2010 and December 2015. Patients were categorized into two groups (clopidogrel users versus clopidogrel non-users), and clinical characteristics and risks of post-stroke infection were compared between the two groups. The inverse probability of treatment weighting using propensity scores for baseline imbalance adjustments was applied. RESULTS: Of the included patients (mean age 67.7 years; men 60.6%), 670 (40.8%) patients were clopidogrel users and 164 (10.0%) patients had post-stroke infection. The proportion of patients with post-stroke infection was significantly lower in clopidogrel users compared to clopidogrel non-users (6.7% vs. 12.2%, P ≤ 0.001). Moreover, clopidogrel users were less likely to be admitted to the intensive care unit (13.3% vs. 35.3%, P = 0.006). A multivariate analysis with inverse probability of treatment weighting revealed that clopidogrel users exhibited a lower risk of post-stroke infection (odds ratio 0.56, 95% confidence interval 0.42-0.75) and intensive care unit admission (odds ratio 0.34, 95% confidence interval 0.22-0.53). CONCLUSIONS: The study suggested that clopidogrel users exhibit a lower risk of infection and develop less severe infections after ischaemic stroke. Further prospective studies are needed.

Crossover from the Ultracold to the Quasiclassical Regime in State-Selected Photodissociation.

Processes that break molecular bonds are typically observed with molecules occupying a mixture of quantum states and successfully described with quasiclassical models, while a few studies have explored the distinctly quantum mechanical low-energy regime. Here, we use photodissociation of diatomic strontium molecules to demonstrate the crossover from the ultracold, quantum regime where photofragment angular distributions strongly depend on the kinetic energy to the quasiclassical regime. Using time-of-flight imaging for photodissociation channels with millikelvin reaction barriers, we explore photofragment energies in the 0.1-300 mK range experimentally and up to 3 K theoretically, and discuss the energy scale at which the crossover occurs. We find that the effects of quantum statistics can persist to high photodissociation energies.