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Early aerobic exercise is associated with improved outcomes following recovery from sport-related concussion (SRC) and is now recommended in guidance for clinicians managing athletes return-to-play. To explore student-athlete experiences of a novel early aerobic exercise intervention. Qualitative study using semi-structured interviews. Loughborough University, UK. Ten rugby union university aged student-athletes (6 men) that had been medically diagnosed with an SRC sustained playing rugby. Three themes divided into eight supporting subthemes were generated. Main findings were: 1) Experience : despite some apprehension over the novel approach, most had a positive experience, 2) Adherence : Participants suggested reasonably good overall adherence to the prescribed exercises but intrinsic and extrinsic factors for non-adherence were identified, 3) Outcomes : the intervention was perceived to help rehabilitation, improve confidence, support retention of athletic identity and, for some, influenced more cautious attitudes toward brain health. The novel early exercise intervention was reasonably well received and adhered to. Unintended benefits included supporting retainment of athletic identity and encouraging precautious health behaviours. As early exercise protocols are refined, these findings will help inform the design and delivery of future interventions, particularly in relation to intensity and diversity of exercises and supporting education. • Controlled early exercise after a Sports-Related Concussion was well received amongst a small sample of rugby union athletes. • Adherence to different aspects of the programme varied, with some constraints to full adherence identified. • The intervention facilitated recovery, confidence and positive health behaviours. • This novel approach may help to improve attitudes towards reporting suspected SRC. [ABSTRACT FROM AUTHOR]

This study combined qualitative and quantitative approaches to evaluate outcomes of isolated nonsyndromic unilateral lambdoid synostosis at the Children's Hospital of Philadelphia. Volumetric, linear, and angular analyses were performed on long-term postoperative and normal control scans. Preoperative and postoperative clinical photographs were evaluated for the presence of dysmorphic frontofacial features. Among 26 included patients, median age of surgery was 10 months and mean postoperative follow-up was 5.9 ± 5.7 years. Two (7.7%) patients underwent secondary cranial vault procedures. At most recent follow-up, 2 (7.7%) subjects reported intermittent headaches. Twenty (90.9%) of 22 patients were assigned Whitaker grade I. Among 9 subjects with long-term imaging at age 11.5 ± 5.3, posterior vault asymmetry, posterior fossa deflection angle, cranial base angle, and ear position asymmetry all remained greater than in the control group. Of subjects included in the frontofacial feature analysis (n = 10), 50% had resolution of all dysmorphic frontofacial features present preoperatively. Overall, most subjects who underwent PVR did not require revisional surgery and had good outcomes both aesthetically and functionally. Despite residual abnormalities in the cranial base and posterior vault, most had resolution of parietal bossing and facial scoliosis. Ear position asymmetry was the most common dysmorphic feature at long-term follow-up. [ABSTRACT FROM AUTHOR]

This study explores visuomotor control in athletes for collision avoidance using virtual reality. Thirty-nine athletes navigated dynamic scenarios, pursuing a virtual target while avoiding two to five virtual defenders. Confirmatory Factor Analysis validated a model that captured two features of scanning behavior based on head movements recorded during activity: the overall amount and temporal pattern. Linear mixed models showed that these features significantly differentiated successful from unsuccessful defender avoidance (p <.05), suggesting that efficient environmental scanning is crucial for collision avoidance while highlighting the potential of visuomotor interventions to reduce collision-related sport injuries. [ABSTRACT FROM AUTHOR]

The wrapping technique aims to protect the nerve when the nerve bed is compromised or more commonly to prevent the recurrence of scar tethering following neurolysis. A wrap provides a physical barrier to scar and helps restore the paraneurial gliding layer. This study aimed to evaluate the results of the AxoGuard® nerve protector, a porcine-derived submucosal extracellular matrix (PECM), used as an adjunct in persistent or recurrent cubital tunnel syndrome (CuTS). This retrospective cohort study evaluated patients diagnosed, between 2012 and 2020, with neuropathic pain who underwent revision surgery. Patients were categorised into Group A (revision surgery only) and Group B (revision surgery and adjunctive PECM nerve wrapping). Disease severity was scored at the baseline and six months post-operatively using the McGowan classification. A linear regression model was used to assess the effect of wrapping the ulnar nerve on the clinical outcome at six months. Fifty-nine nerves were treated; among them, adjunctive PECM wrapping was used in 32 nerves. Disease severity at baseline was similar between the groups. After adjusting for differences in baseline characteristics, participants in Group B improved with a significant difference of 0.43 McGowan points over Group A (95% CI (0.01–0.86), p = 0.049). There were no implant-related complications. Group B improved with excellent or good outcomes in 84.4% patients at the final follow-up. Persistent or recurrent CuTS were associated with neuropathic pain and significant nerve scar tether. The use of PECM appears to lead to improved clinical symptoms, possibly by reducing adhesions and encouraging physiological glide. Level III evidence. [ABSTRACT FROM AUTHOR]

As the rate of total shoulder arthroplasty (TSA) and preoperative benzodiazepine use rise, there is an increased need to understand the impact of preoperative benzodiazepine use on postoperative opioid consumption following TSA, especially amid the current opioid epidemic. The relationship between preoperative benzodiazepine use and chronic opioid use postoperatively has been well described following other orthopedic procedures; however, the impact on patients undergoing TSA remains unclear. This study aims to identify the impact of preoperative benzodiazepine use on opioid use following TSA. A retrospective chart review of 4488 patients undergoing primary TSA (Current Procedural Terminology code 23472) at a single institution from 2014 to 2022 was performed. Patient demographics, surgical variables, comorbidities, Distressed Communities Index (DCI), and clinical outcomes, including readmission and revision, were collected. The Charlson Comorbidity Index (CCI) was used to assess preoperative health status. Opioid use in morphine milligram equivalents (MMEs) and benzodiazepine use were also recorded using the Prescription Drug Monitoring Program Database. Opioid use was collected at 30-, 60-, and 90-day intervals both before and after each patient's date of surgery. Statistical analysis included stepwise logistic regression to identify variables independently affecting benzodiazepine use pre- and postoperatively. Overall, 16% of patients used benzodiazepines within 90 days before their date of surgery. Of those patients, 46.4% were also using preoperative opioids, compared with just 30.0% of patients who were benzodiazepine-naïve (P <.001). Preoperative benzodiazepine use was also associated with increased pre- and postoperative total opioid use in MMEs and the number of opioid prescriptions across all time points when compared to benzodiazepine-naïve patients (P <.001). Furthermore, 37.4% of preoperative benzodiazepine users went on to prolonged opioid use (filled prescriptions >30 days after surgery) compared to 19.0% of those who were benzodiazepine-naïve (P <.001). This study demonstrates a significant association between preoperative benzodiazepine use and increased and prolonged opioid use following TSA. Further exploration of risk factors contributing to preoperative benzodiazepine use may help to reduce overall opioid use in patients undergoing TSA. [ABSTRACT FROM AUTHOR]

To test the hypothesis that weight loss following bariatric surgery is associated with a reduced risk of developing carpal tunnel syndrome (CTS) compared with obese patients who do not undergo bariatric surgery. We performed a cohort study using data from the Swedish nationwide healthcare registries. Patients aged 18–79 years who underwent bariatric surgery from 2006 to 2019 were propensity score (PS)–matched to up to 2 obese bariatric surgery-free patients ("unexposed patients"). Cox proportional hazard regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CIs) to compare the incidence of CTS among bariatric surgery patients to obese unexposed patients both overall and divided by subgroups of age, sex, bariatric surgery type, and duration of follow-up. In total, 40,619 bariatric surgery patients were PS-matched to 63,540 obese unexposed patients who did not undergo surgery. Bariatric surgery was not associated overall with CTS (HR 0.98, 95% CI 0.91–1.05). There was a 23% decreased risk of CTS incidence observed within >1–3 years after bariatric surgery (HR 0.77, 95% CI 0.68–0.88). Decreased CTS risks were observed among bariatric surgery patients aged 18–34 years (HR 0.87, 95% CI 0.74–1.01) and those who underwent sleeve gastrectomy (HR 0.81, 95% CI 0.63–1.03), but these risks did not reach significance level compared with obese unexposed patients. However, there was a 20% increased CTS risk after 6 years (HR 1.20, 95% CI 1.05–1.36). Our results suggest that marked weight does not have a lasting impact on the reduction of CTS incidence. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Re-Os isochron age of the Aoertuokenashi Mn deposit is 302 ± 9 Ma. • A mantle plume promoted Mn mineralization in the Western Kunlun Orogen. • Back-arc basin with starving basin features is favorable for Mn-carbonate. • Organic matter played an important role in the Mn deposition. • Microbial mediation enhanced Mn mineralization. The Aoertuokanashi deposit located in the Western Kunlun Orogen is the first known Late Carboniferous large high-grade carbonate-hosted Mn deposit in the world and it has been mined since 2018. The deposit is considered to have formed in a back-arc basin developed during the northward subduction of the Paleo-Tethys Ocean beneath the Tarim Block. The Re-Os isotope isochron age of Mn ore at the Aoertuokanashi deposit is 302 ± 9 Ma. The minimum initial 187Os/188Os values obtained from the deposit is 0.28, which indicates the presence of a mantle source for the mineralization. The Aoertuokanashi deposit is similar in age to the 301 ± 5 Ma Wajilitag kimberlite in the Tarim Block, which is considered to be the initial magmatic pulse triggered by the Tarim mantle plume. The Late Carboniferous Aoertuokanashi Mn deposit was likely promoted by igneous activity from the Tarim mantle plume. The Aoertuokanashi deposit shows geochemical characteristics of hot water activity in a back-arc basin. The Mn mineralization is hosted in the restricted platform facies. Framboidal pyrite, typical biomat, and authigenic quartz are observed in the Mn deposit, indicating the influence of microbial processes. The sedimentary facies show a starving basin feature that can enhance microbial mediation. The δ13C V-PDB values of mineralized rocks (from −19.5 to −8.2 ‰) are more negative than those of wall rocks (from −5.3 to + 4.2 ‰), whereas the δ13C V-PDB values (around −29 ‰) of kerogen for the Mn ore are significantly lower than those of the whole rock. These compositions indicate that the reducing function of organic matter played an important role in Mn mineralization. In the inferred extensional tectonic environment, under the influence of a mantle plume, the stratum with strong hot water activities and a large amount of organic matter becomes the focal point for the formation of carbonate type manganese ore deposit. [ABSTRACT FROM AUTHOR]

Preoperative opioid users experience worse outcomes and higher complication rates compared to opioid-naïve patients following shoulder arthroplasty. This study evaluates the effects of socioeconomic status, as measured by the Distressed Communities Index (DCI), on pre- and postoperative opioid use and its influence on clinical outcomes such as readmission and revision surgery. A retrospective review of patients who underwent primary shoulder arthroplasty (Current Procedural Terminology code 23472) from 2014 to 2022 at a single academic institution was performed. Exclusion criteria included arthroplasty for fracture, active malignancy, and revision arthroplasty. Demographics, Charlson Comorbidity Index, DCI, and clinical outcomes including 90-day readmission and revision surgery were collected. Patients were classified according to the DCI score of their zip code. Using the Prescription Drug Monitoring Program database, patient pre- and postoperative opioid use in morphine milligram equivalents was gathered. Individuals from distressed communities used more opioids within 90 days preoperatively compared to patients from prosperous, comfortable, mid-tier, and at-risk populations, respectively. Patients from distressed communities also used significantly more opioids within 90 days postoperatively compared with prosperous, comfortable, and mid-tier, respectively. Of patients from distressed communities, 35.1% developed prolonged opioid use (filling prescriptions >30 days after surgery), significantly more than all other cohorts. Among all patients, 3.5% were readmitted within 90 days and were more likely to be prolonged opioid users (38.9 vs. 21.3%, P <.001). Similarly, 1.5% of patients underwent revision surgery. Those who underwent revision were significantly more likely to be prolonged opioid users (38.2 vs. 21.7%, P =.002). Shoulder arthroplasty patients from distressed communities use more opioids within 90 days before and after their surgery and are more likely to become prolonged opioid users, placing them at risk for readmission and revision surgery. Identifying patients at an increased risk for excess opioid use is essential to employ appropriate strategies that minimize the detrimental effects of prolonged use following surgery. [ABSTRACT FROM AUTHOR]

Phytic acid (inositol hexaphosphate/IP6) is a versatile chemical that is abundant in nature and is required for a variety of biological processes. It is harnessed in a wide range of fields, including drug discovery, daily supplies, chemical industries, medicine, and dentistry. IP6 is becoming increasingly popular in dentistry, with promising results. Several properties, such as cariostatic ability, beneficial impact on enamel disintegration, and anti-plaque, anti-tartar, and dental adhesive-forming properties, have been investigated thus far. Due to many constraints in the literature, there was a point in time when IP6 received less attention, which impacted knowledge in this field. Nevertheless, the positive outcomes of the flourishing of IP6 have recently been reconsidered from a number of papers that have improved our understanding of its modes of action in the aforementioned applications. The role of phytic acid in refining the properties and manoeuvring of dental resources is being investigated in novel endeavors in treating diseases of pulp and tissues supporting tooth structure, but to show its novel therapeutic potential, more precisely calibrated clinical trials are needed. This review examines and discusses the various uses proposed in the literature, as well as the applications of IP6 in dentistry. [ABSTRACT FROM AUTHOR]

Preventive strategies should be the utmost priority when dealing with diverse patients suffering from malignant ventricular arrhythmia (MVA) that can lead to sudden cardiac death (SCD). Electrocardiogram (ECG) data is commonly used as a predictor for MVA predictive models. In this study, all ECG signals from MIT-BIH databases were fragmented into five-minute durations with a frequency sampling of 128 Hz. To solve the absence of hybrid optimizations in Machine Learning (ML) models, a novel Variational Quantum Neural Network (VQNN) was invented. Empowered by deep learning capabilities and optimized quantum circuits design, VQNN achieved remarkable performances designated by an accuracy of up to 95.1%, a perfect 100% recall, and a 95.2% score of the area under the Receiver Operating Characteristic curve (AUC ROC) with Conjugate Gradient as an optimizer and EfficientSU2 as a quantum ansatz. Despite the susceptibility to quantum noise, this research settles a new trajectory of utilizing quantum variational algorithms to predict and expand its applicability for MVA cases. [ABSTRACT FROM AUTHOR]

To compare intraoperative labral characteristics and minimum 2-year functional outcomes of allograft labral reconstruction in primary versus revision hip arthroscopy across multiple orthopaedic centers. A retrospective multicenter hip arthroscopy registry was queried for patients with completed labral reconstruction surgeries from January 2014 to March 2023 with completed 2-year international Hip Outcome Tool-12 (iHOT-12) reports. Age, sex, and major intraoperative variables also were collected. Patients were placed in cohorts based on whether their arthroscopic allograft labral reconstruction was a primary procedure or secondary procedure (reconstruction following failed hip arthroscopy). One-way analysis of variance was performed on continuous variables. χ2 test was performed on categorical variables. Achievement of minimal clinically important difference (MCID), Patient Acceptable Symptom State (PASS), and Substantial Clinical Benefit (SCB) also was assessed. In total, 77 patients met the inclusion and exclusion criteria and had complete information. The primary reconstruction group (n = 50) was significantly older than the secondary reconstruction group (n = 27) (47.5 ± 10.5 vs 39.1 ± 8.8 years; P =.001). In both cohorts, most patients had labral bruising, advanced labral degeneration, and/or grade III complexity of labral tearing. There was no difference in any recorded intraoperative findings (P =.160, P =.783, P =.357, respectively). Each cohort experienced significant improvement in iHOT-12 scores (P <.0001). However, patients undergoing secondary labral reconstruction reported inferior iHOT-12 scores (60.1 ± 29.2 vs 74.8 ± 27.0; P =.030). Patients undergoing primary reconstruction were more likely to reach MCID, PASS, and nearly normal SCB (92 vs 66.7%, P =.024; 68.0 vs 40.7%, P =.021; 76.0 vs 48.1%, P =.014, respectively). Primary and secondary allograft labral reconstruction show clinical improvement, but primary reconstruction demonstrates better outcomes and greater percentage of patients reaching MCID, PASS, and nearly normal SCB than reconstruction in the revision setting. Level III, retrospective comparative prognostic case-control study. [ABSTRACT FROM AUTHOR]

The non-genetic factors predisposing to trigger finger (TF) have mostly been characterised in small studies from individual institutions. Here, we aimed to provide a more complete picture of TF and its associations. This case-control study used cross-sectional data from the UK Biobank population-based cohort to identify and determine the strength of associations of phenotypic variables with TF. We performed multivariable logistic regression of a multitude of phenotypic factors associated with TF. We identified 2250 individuals with medical and surgical diagnostic codes for TF, and 398,495 controls. TF was found to be significantly associated with age (OR 1.04, 95% CI 1.03–1.04, P < 2.23 × 10 − 308 ), female sex (OR 1.22, 95% CI 1.08–1.39, P = 2.35 × 10 − 3 ), body mass index (OR 1.10, 95% CI 1.04–1.16, P = 5.52 × 10 − 4 ), carpal tunnel syndrome (OR 9.59, 95% CI 8.68–10.59, P < 2.23 × 10 − 308 ), Dupuytren's disease (OR 4.89, 95% CI 4.06–5.89, P < 2.23 × 10 − 308 ), diabetes mellitus without complications (OR 1.35, 95% CI 1.15–1.58, P = 2.03 × 10 − 4 ) and with complications (OR 2.46, 95% CI 1.90–3.17, P = 4.98 × 10 − 12 ), HbA1c (OR 1.01, 95% CI 1.01–1.02, P = 8.99 × 10 − 9 ), hypothyroidism (OR 1.24, 95% CI 1.07–1.43, P = 4.75 × 10 − 3 ) and rheumatoid arthritis (OR 1.33, 95% CI 1.06–1.68, P = 0.014). Our results provide evidence supporting the well-known risk factors such as diabetes mellitus, carpal tunnel syndrome, age and female sex. Furthermore, we can confirm putative associations such as hypothyroidism, obesity and rheumatoid arthritis, while providing evidence against others such as hypertension and hyperlipidaemia. A novel finding arising from this study is the strong association with Dupuytren's disease. Our study design allowed us to identify these associations as being independent from carpal tunnel syndrome, thereby indicating a shared pathophysiology between this disease and TF. [ABSTRACT FROM AUTHOR]

Literature reporting on the prosthetic survival and complications of implant-retained prostheses in patients with head and neck cancer is sparse. The purpose of this retrospective study was to present the survival rates and complication-free survival rates of both fixed and removable implant-retained oral prostheses in patients with head and neck cancer while also reporting on the frequency and causes of failure and complications for each prosthesis type. A retrospective analysis of the prosthetic survival rates and complication-free survival rates of implant-retained oral prostheses and the frequency and causes of failure and complications in patients with head and neck cancer treated in a regional unit from 2012 to 2017 was performed. Differences in categorical and continuous data were assessed for statistical significance by using the Pearson chi-squared test, Fisher exact test, t test, and analysis of variance as appropriate. Cox proportional hazard regression models were fitted to evaluate the association between prostheses type, clinical and medical factors, and the outcomes of survival and complication-free survival. Descriptive statistics were used to analyze the frequency and type of prosthetic complications. The sample was composed of 153 patients diagnosed with head and neck cancer who had completed implant-retained prosthodontic rehabilitation and had been provided with 221 prostheses. The 5-year survival rate was 87% for maxillary fixed prostheses, 79% for mandibular fixed, 66% for maxillary removable, and 50% for mandibular removable. Hazard ratios were calculated showing that the 5-year survival rate of a mandibular removable prosthesis (HR=5.1; 95% CI 1.60-16.25) (P =.006) was greater than that of a maxillary fixed prosthesis (HR=1.0). The 5-year complication-free survival rate was highest for mandibular fixed prostheses (62%), followed by maxillary fixed (58%), maxillary removable (36%), and mandibular removable prostheses (29%). Hazard ratios showed that the 5-year survival rate of maxillary removable (HR=1.91; 95% CI 1.01-3.66) (P =.048) and mandibular removable prosthesis (HR=2.29; 95% CI 1.23-4.25) (P =.009) was greater than that of a maxillary fixed prosthesis (HR=1.0). Variables of radiotherapy, grafting, age, and sex and their influence on the survival rate and complication-free survival rate were assessed but were not statistically significant. This evaluation indicated that fixed implant-retained prostheses had a higher 5-year survival rate and 5-year complication-free survival rate than removable implant-retained prostheses in patients with head and neck cancer. [ABSTRACT FROM AUTHOR]

Selective intra-arterial radiotherapy (SIRT) is a technique which has evolved over the past 30 years. In present this is primarily used to treat primary and secondary tumors in the liver. The technique normally depends on the delivery of a therapeutic radiopharmaceutical or radiolabeled particulate via a radiologically placed intra-arterial catheter in the hepatic artery. This is because most of these tumors have a single arterial blood supply but normal hepatocytes are supplied by both the hepatic artery and portal vein. Initially, this was done with I-131 labelled poppy seed oil but this technique was only used in a few centers. The technique became more popular when Y-90 particulates become widely available. Early results were promising but in phase 3 randomized controlled trials resulted in disappointing results compared to systemic chemotherapy. More recent work however, have shown that increasing the radiation dose to the tumor to at least 60Gy and combining with more effective systemic therapies are starting to produce better clinical results. There have also been advances in the angiographic methods used to make this into a day-case technique and the use of new radionuclides such as Ho-166 and Re-188 provides a wider range of possible SIRT techniques. [ABSTRACT FROM AUTHOR]

Seasonal underground hydrogen storage (UHS) in porous media provides an as yet untested method for storing surplus renewable energy and balancing our energy demands. This study investigates the technical suitability for UHS in depleted hydrocarbon fields and one deep aquifer site in Taranaki Basin, Aotearoa New Zealand. Prospective sites are assessed using a decision tree approach, providing a "fast-track" method for identifying potential sites, and a decision matrix approach for ranking optimal sites. Based on expert elicitation, the most important factors to consider are storage capacity, reservoir depth, and parameters that affect hydrogen injectivity/withdrawal and containment. Results from both approaches suggest that Paleogene reservoirs from gas (or gas cap) fields provide the best option for demonstrating UHS in Aotearoa New Zealand, and that the country's projected 2050 hydrogen storage demand could be exceeded by developing one or two high ranking sites. Lower priority is assigned to heterolithic and typically finer grained, labile and, clay-rich Miocene oil reservoirs, and to deep aquifers that have no proven hydrocarbon containment. • UHS could provide temporary storage for a large surplus of renewable energy. • The technical feasibility of potential storage sites in Taranaki Basin is assessed. • Two methods for site evaluation are applied, using multi-criteria decision analysis. • Depleted gas fields are considered the best option for demonstrating UHS technology. • The projected 2050 storage capacity demand for NZ could be met by developing 1–2 sites. [ABSTRACT FROM AUTHOR]

Refractory vasodilatory shock, or vasoplegia, is a pathophysiologic state observed in the intensive care unit and operating room in patients with a variety of primary diagnoses. Definitions of vasoplegia vary by source but are qualitatively defined clinically as a normal or high cardiac index and low systemic vascular resistance causing hypotension despite high-dose vasopressors in the setting of euvolemia. This definition can be difficult to apply to patients undergoing mechanical circulatory support (MCS). A large body of mostly retrospective literature exists on vasoplegia in the non-MCS population, but the increased use of temporary MCS justifies an examination of vasoplegia in this population. MCS, particularly extracorporeal membrane oxygenation, adds complexity to the diagnosis and management of vasoplegia due to challenges in determining cardiac output (or total blood flow), lack of clarity on appropriate dosing of noncatecholamine interventions, increased thrombosis risk, the difficulty in determining the endpoints of adequate volume resuscitation, and the unclear effects of rescue agents (methylene blue, hydroxocobalamin, and angiotensin II) on MCS device monitoring and function. Care teams must combine data from invasive and noninvasive sources to diagnose vasoplegia in this population. In this narrative review, the available literature is surveyed to provide guidance on the diagnosis and management of vasoplegia in the temporary MCS population, with a focus on noncatecholamine treatments and special considerations for patients supported by extracorporeal membrane oxygenation, transvalvular heart pumps, and other ventricular assist devices. [ABSTRACT FROM AUTHOR]

• Infants with BPD receiving higher levels of respiratory support on discharge from hospital is associated with poorer NDI. • Understanding the relative risks of NDI may facilitate better-informed counselling of parents regarding outcomes at age 3 years. • Subclassifying BPD infants based on levels of respiratory support received at home is a pragmatic way to predict outcome. The reader will come to appreciate that: • The likelihood of infants with BPD developing poorer childhood neurodevelopmental outcomes is associated with the level of respiratory support provided on discharge from hospital. • Understanding the relative risks of neurodevelopmental impairment may facilitate better-informed counselling of parents regarding clinical outcomes at age 3 years. To investigate the neurodevelopmental outcomes for preterm infants born < 29 weeks gestation with/without bronchopulmonary dysplasia (BPD). Preterm infants < 29 weeks' gestation born 2007–2018 in New South Wales and the Australian Capital Territory, Australia, were included. Infants who died < 36 weeks' postmenstrual age and those with major congenital anomalies were excluded. Subjects were assessed at 18–42 months corrected age using the Bayley Scales of Infant Development, 3rd edition. 1436 infants without BPD (non-BPD) and 1189 infants with BPD were followed. The BPD group, 69 % infants were discharged without respiratory support (BPD1), 29 % on oxygen (BPD2) and 2 % on pressure support/tracheostomy (BPD3). Moderate neurodevelopmental impairment (NDI) was evident in 5.7 % of non-BPD infants, 11 % BPD1, 15 % BPD2, 15 % BPD3 infants. Severe NDI was seen in 1.7 % non-BPD infants, 3.4 % BPD1, 7.3 % BPD2, 35 % BPD3 infants. After adjusting for confounders, infants with BPD2 (OR 2.24, 99.9 % CI 1.25 to 5.77) or BPD3 (OR 5.99, 99.9 % CI 1.27 to 46.77) were more likely to have moderate-severe NDI compared to non-BPD infants. The majority of infants with BPD were discharged home without respiratory support and had better neurocognitive outcomes in early childhood compared to those that required home-based oxygen or respiratory support. [ABSTRACT FROM AUTHOR]

The reader will come to appreciate that: • Infection occurs through percutaneous inoculation or inhalation with contaminated soil and water. • Diagnosis of melioidosis can be difficult because of its diverse presentation. • Melioidosis is increasingly being diagnosed around the world. • Greater consideration for melioidosis in protracted or atypical pneumonia is warranted regardless of location. Melioidosis is a tropical infectious disease caused by the saprophytic gram-negative bacterium Burkholderia pseudomallei. Despite the infection being endemic in southeast Asia and northern Australia, the broad clinical presentations and diagnostic difficulties limit its early detection, particularly in children. Melioidosis more commonly affects the immunocompromised and adults. Melioidosis is increasingly being diagnosed around the world and whole-genome sequencing indicates that these cases are not linked with travel to endemic areas. Research has concentrated on the adult population with limited experience reported in the care of this uncommon, but potentially fatal condition in children presenting with bacteraemia and pneumonia. [ABSTRACT FROM AUTHOR]

The reader will come to appreciate: • Aspects of patients' reasoning for non-adherence with asthma medications. • How adherence is measured. • Recent developments in technology allowing more accurate measures of asthma control. • Ways of individualising patient outcomes. • The utility of smart-inhalers in improving asthma control. Poor adherence is an important factor in unstable disease control and treatment failure. There are multiple ways to monitor a patient's adherence, each with their own advantages and disadvantages. The reasons for poor adherence are multi-factorial, inter-related and often difficult to target for improvement. Although practitioners can implement different methods of adherence, the ultimate aim is to improve health outcomes for the individual and the health care system. Asthma is a common airway disease, particularly diagnosed in children, often treated with inhaled corticosteroids and long-acting bronchodilators. Due to the disease's tendency for exacerbations and consequently, when severe will require unscheduled health care utilisation including hospital admissions, considerable research has been done into the effects of medication adherence on asthma control. This review discusses the difficulties in defining adherence, the reasons for and consequences of poor adherence, and the methods of recording and improving adherence in asthma patients, including an in-depth analysis of the uses of smart inhalers. [ABSTRACT FROM AUTHOR]

This study compares condylar volumetric asymmetry and facial asymmetry in patients with cleft lip and/or palate (CLP) and controls. The mandibular condyle is important to facial growth, but its role in facial asymmetry for those with CLP has not been described. Condylar volumes and mandibular asymmetry were retrospectively calculated using Mimics Version 23.0 (Materialise, Leuven, Belgium) from patients with CLP undergoing computed tomography (CT) imaging and a cohort of controls. A total of 101 participants, 60 with CLP and 41 controls, had mean condylar volumetric asymmetry of 16.4 ± 17.4 % (CLP) and 6.0 ± 4.0 % (controls) (p = 0.0002). Patients with CLP who had clinically significant chin deviation (>4 mm) had more asymmetric condyles than those without significant chin deviation (p = 0.003). The chin deviated toward the smaller condyle in patients with facial asymmetry more often than in patients without facial asymmetry (81 % vs. 62 %, p = 0.033). While controls had some degree of condylar asymmetry, it tended to be milder and not associated with facial asymmetry. There is a greater degree of condylar volumetric asymmetry in patients with CLP compared to individuals in the general population. Clinically significant facial asymmetry in CLP is associated with a higher degree of condylar asymmetry, with the facial midline deviating toward the smaller condyle. [ABSTRACT FROM AUTHOR]

Prehabilitation comprises multidisciplinary preoperative interventions including exercise, nutritional optimisation and psychological preparation aimed at improving surgical outcomes. The aim of this systematic review and meta-analysis was to determine the impact of prehabilitation on postoperative outcomes in frail and high-risk patients undergoing major abdominal surgery. Embase, Medline, CINAHAL and Cochrane databases were searched from January 2010 to January 2023 for randomised clinical trials (RCTs) and observational studies evaluating unimodal (exercise) or multimodal prehabilitation programmes. Meta-analysis was limited to length of stay (primary end point), severe postoperative complications (Clavien-Dindo Classification ≥ Grade 3) and the 6-minute walk test (6MWT). The analysis was performed using RevMan v5.4 software. Sixteen studies (6 RCTs, 10 observational) reporting on 3339 patients (1468 prehabilitation group, 1871 control group) were included. The median (interquartile range) age was 74.0 (71.0–78.4) years. Multimodal prehabilitation was applied in fifteen studies and unimodal in one. Meta-analysis of nine studies showed a reduction in hospital length of stay (weighted mean difference −1.07 days, 95 % CI −1.60 to −0.53 days, P < 0.0001, I 2 = 19 %). Ten studies addressed severe complications and a meta-analysis suggested a decline in occurrence by up to 44 % (odds ratio 0.56, 95 % CI 0.37 to 0.82, P < 0.004, I 2 = 51 %). Four studies provided data on preoperative 6MWT. The pooled weighted mean difference was 40.1 m (95 % CI 32.7 to 47.6 m, P < 0.00001, I 2 = 24 %), favouring prehabilitation. Given the significant impact on shortening length of stay and reducing severe complications, prehabilitation should be encouraged in frail, older and high-risk adult patients undergoing major abdominal surgery. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI)-based autocontouring in radiation oncology has potential benefits such as standardization and time savings. However, commercial AI solutions require careful evaluation before clinical integration. We developed a multidimensional evaluation method to test pretrained AI-based automated contouring solutions across a network of clinics. Curated data included 121 patient planning computed tomography (CT) scans with a total of 859 clinically approved contours used for treatment from 4 clinics. Regions of interest (ROIs) were generated with 3 commercial AI-based automated contouring software solutions (AI1, AI2, AI3) spanning the following disease sites: brain, head and neck (H&N), thorax, abdomen, and pelvis. Quantitative agreement between AI-generated and clinical contours was measured by Dice similarity coefficient (DSC) and Hausdorff distance (HD). Qualitative assessment was performed by multiple experts scoring blinded AI-contours using a Likert scale. Workflow and usability surveying was also conducted. AI1, AI2, and AI3 contours had high quantitative agreement in 27.8%, 32.8%, and 34.1% of cases (DSC >0.9), performing well in pelvis (median DSC = 0.86/0.88/0.91) and thorax (median DSC = 0.91/0.89/0.91). All 3 solutions had low quantitative agreement in 7.4%, 8.8%, and 6.1% of cases (DSC <0.5), performing worse in brain (median DSC = 0.65/0.78/0.75) and H&N (median DSC = 0.76/0.80/0.81). Qualitatively, AI1 and AI2 contours were acceptable (rated 1-2) with at most minor edits in 70.7% and 74.6% of ROIs (2906 ratings), higher for abdomen (AI1: 79.2%) and thorax (AI2: 90.2%), and lower for H&N (29.0/35.6%). An end-user survey showed strong user preference for full automation and mixed preferences for accuracy versus total number of structures generated. Our evaluation method provided a comprehensive analysis of both quantitative and qualitative measures of commercially available pretrained AI autocontouring algorithms. The evaluation framework served as a roadmap for clinical integration that aligned with user workflow preference. [ABSTRACT FROM AUTHOR]

To demonstrate the feasibility and potential of using a second-generation prototype photon-counting computed tomography (CT) system to provide simultaneous high spatial resolution images and high spectral resolution material information across a range of routine imaging tasks using clinical patient exposure levels. The photon-counting system employs an innovative silicon-based photon-counting detector to provide a balanced approach to ultra-high-resolution spectral CT imaging. An initial cohort of volunteer subjects was imaged using the prototype photon-counting system. Acquisition technique parameters and radiation dose exposures were guided by routine clinical exposure levels used at the institution. Images were reconstructed in native slice thickness using an early version of a spectral CT reconstruction algorithm Samples of images across a range of clinical tasks were selected and presented for review. Clinical cases are presented across inner ear, carotid angiography, chest, and musculoskeletal imaging tasks. Initial reconstructed images illustrate ultra-high spatial resolution imaging. The fine detail of small structures and pathologies is clearly visualized, and structural boundaries are well delineated. The prototype system additionally provides concomitant spectral information with high spatial resolution. This initial study demonstrates that routine imaging at clinically appropriate patient exposure levels is feasible using a novel deep-silicon photon-counting detector CT system. Furthermore, a deep-silicon detector may provide a balanced approach to photon-counting CT, providing high spatial resolution imaging with simultaneous high-fidelity spectral information. [ABSTRACT FROM AUTHOR]

People with type 1 diabetes (T1D) are advised by health care professionals to target mild hyperglycaemia before and during exercise, to reduce the risk of hypoglycaemia. This review aimed to summarise the available evidence on the effects of acute hyperglycaemia on sports and exercise performance in T1D. Systematic review and meta-analysis. Medline, EMBASE, CENTRAL, and Web of Science were searched until 29th May 2023 for studies investigating the effects of acute hyperglycaemia on any sports or exercise performance outcome in T1D. Random-effects meta-analysis was performed using standardised mean differences (SMD) when more than one study reported data for similar outcomes. Certainty of evidence for each outcome was assessed using GRADE. Seven studies were included in the review, comprising data from 119 people with T1D. Meta-analysis provided moderate-certainty evidence that acute hyperglycaemia does not significantly affect aerobic exercise performance (SMD − 0.17; 95 % CI − 0.59, 0.26; p = 0.44). There is low- or very-low certainty evidence that acute hyperglycaemia has no effect on anaerobic (two outcomes), neuromuscular (seven outcomes) or neurocognitive performance (three outcomes), except impaired isometric knee extension strength. One study provided low-certainty evidence that the performance effects of hyperglycaemia may depend on circulating insulin levels. Acute hyperglycaemia before or during exercise appears unlikely to affect aerobic performance to an extent that is relevant to most people with T1D, based on limited evidence. Future research in this field should focus on anaerobic, neuromuscular and neurocognitive performance, and examine the relevance of circulating insulin levels. [ABSTRACT FROM AUTHOR]

Maintenance of aged power equipment is a proven technique for establishing systems reliability and longevity. It is extensively relevant when combined with Condition Based Maintenance (CBM) approaches for predicting power system infrastructure life, especially with imminent obsolescence. The research focuses on distribution companies with mixed aged power infrastructure, which continuously degradate. A significant setback in older systems is the scarcity of replacement parts leading to unplanned investment in substantial infrastructure due to unexpected failed components that are no longer in production. To guarantee excellent infrastructure health in older equipment, utility companies should consider applying Condition Based Maintenance (CBM) using Artificial Neural Network (ANN) to stabilize older equipment and restore malfunctioning assets. Studies have shown that the life span of older equipment can be extended when adequate maintenance strategies are put in place through the prediction of possible failures using equipment inspections and risk matrix. CBM's strategy improved the Key Performance Indicator (KPIs) System Average Interruption Duration Index (SAIDI) has improved by lowering the average monthly customers power interruptions by 19,15 % lesser time spent without electricity. The System Average Interruption Frequency Index (SAIFI) was improved by lowering the average monthly power interruptions frequency by 20,63% lesser outage frequency. The Distribution Supply Loss Index (DSLI) was improved by dropping the average monthly power losses by 7,5% power losses saved. The Customers Average Interruption Duration Index (CAIDI) was improved by lowering the average customer interruption by 36.1% improvement from the average period before the CBM optimization. The Average System Availability Index (ASAI) was improved by shortening the average annual interruption durations by 1,36%. The ASUI was improved by increasing the average duration of electrical power availability by 1.28%. The optimization of CBM was measured over 24 moths period. [ABSTRACT FROM AUTHOR]

Considerable variation in practice exists in the prevention, diagnosis, and treatment of periprosthetic joint infection (PJI), which is a devastating complication for patients and surgeons. The consensus principle has been increasingly embraced by the orthopaedic community to help guide practice, especially where high-level evidence remains unavailable. The third United Kingdom Periprosthetic Joint Infection (UK PJI) Meeting was held in Glasgow on April 1, 2022, with more than 180 delegates in attendance, representing orthopaedics, microbiology, infectious diseases, plastic surgery, anesthetics, and allied health professions, including pharmacy and arthroplasty nurses. The meeting comprised a combined session for all delegates, and separate breakout sessions for arthroplasty and fracture-related infection. Consensus questions for each session were prepared in advance by the UK PJI working group, based upon topics that were proposed at previous UK PJI Meetings, and delegates participated in an anonymized electronic voting process. We present the findings of the combined and arthroplasty sessions of the meeting in this article, and each consensus topic is discussed in relation to the contemporary literature. [ABSTRACT FROM AUTHOR]

Health benefits packages (HBPs), which define specific health services that can be offered for free or at a reduced cost to fit within public revenues, have been recommended for over 30 years to maximize population health in resource-limited settings. However, there remain gaps in defining and operationalizing HBPs. We propose a combination of design and prioritization methods along with practical strategies to improve the implementation of future iterations of the HBP in Malawi. For HBP development for Malawi's Third Health Sector Strategic Plan, we combined cost-effectiveness analysis with a quantitative, consultative multicriteria decision analysis. Throughout the process of development, we documented challenges and opportunities to improve HBP design and application. The primary and secondary HBP included 115 interventions. However, the definition of an HBP is just one step toward focusing limited resources, with functional operationalization as the most critical component. Full implementation of previous HBPs has been limited by challenges in aid coordination with the misalignment of nonfungible vertical donor funding for the HBP without accounting for the complexity and interconnectedness of the health system. Opportunities for improved application include creation of a complementary minimum health service package to guide overall resource inputs through an integrative approach. We believe that expanded participatory HBP methods that consider value, equity, and social considerations, along with a shift to providing integrated health service packages at all levels of care, will improve the efficiency of using scarce resources along the journey to universal health coverage. • "Essential health packages," or health benefits packages (HBPs), have been recommended to define priority services to be funded from public and sometimes donor budgets to improve resource-use efficiency in service delivery and reduce the burden of disease and poverty. Malawi has been implementing HBPs for over 20 years with challenges of limited resources and lack of enforcement. • For Malawi's Health Sector Strategic Plan III for 2023 to 2030, we complemented traditional methods of defining HBPs using a cost-effectiveness-based prioritization of preventative, promotive, diagnostic, treatment, rehabilitative, and palliative care interventions with a multicriteria decision analysis. This enabled a systematic inclusion of interventions without available cost-effectiveness data through use of quantitative methods to consider additional criteria, such as equity. We discuss challenges and opportunities for the Health Sector Strategic Plan III and HBP implementation that could be contextualized to similar settings. • Our experience defining the HBP proposes using deliberative and quantitative prioritization for a contextualized HBP with the vision to base future HBPs on an integrated implementation packages of health services instead of individual "list-based" interventions. This approach aims to facilitate integrated and accessible care delivery to achieve universal health coverage. [ABSTRACT FROM AUTHOR]

Focusing on the East, Central, and Southern African region, this study examines both regional and country-level initiatives aimed at promoting multisectoral collaboration to improve population health and the methods for their economic evaluation. We explored the interventions that necessitate cooperation among policymakers from diverse sectors and the mechanisms that facilitate effective collaboration and coordination across these sectors. To gain insights into the demand for multisectoral collaboration in the East, Central, and Southern African region, we presented 3 country briefs, highlighting policy areas and initiatives that have successfully incorporated health-promoting actions from outside the health sector in Zimbabwe, Uganda, and Malawi. Additionally, we showcased initiatives undertaken by the Ministry of Health in each country to foster coordination with national and international stakeholders, along with existing coordination mechanisms established for intersectoral collaboration. Drawing on these examples, we identified the primary challenges in the economic evaluation of multisectoral programs aimed at improving health in the region. We illustrated how decision making in reality differs from the traditional single-sector and single-decision-maker perspective commonly used in cost-effectiveness analyses. To ensure economic evaluations can inform decision making in diverse settings and facilitate regional collaboration, we highlighted 3 fundamental principles: identifying policy objectives, defining the perspective of the analysis, and considering opportunity costs. We emphasized the importance of adopting a flexible and context-specific approach to economic evaluation. Through this work, we contribute to bridging the gap between theory and practice in the context of intersectoral activities aimed at improving health outcomes. • The World Health Organization has been emphasizing the importance of multisectoral collaboration to improve health for decades. However, multisectoral resource allocation and priority setting requires mechanisms and initiatives for articulating interdependencies, harmonizing strategies, and elaborating pathways to change. • We explore the practice and the methods of economic evaluation that could be adopted to facilitate more effective and efficient multisectoral coordination for improvement of population health in the East, Central, and Southern Africa Health Community region. We first provide an example of cross-sectoral coordination for health at the East, Central, and Southern African region level, then focus on 3 countries—Zimbabwe, Uganda, and Malawi. • With this work we illustrate that, despite the complexities of intersectoral decision-making, economic evaluation tools offer a systematic approach for allocating scarce resources effectively. [ABSTRACT FROM AUTHOR]

Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD). Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation. Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochondria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion. Following 4 hours of ESHP perfusion, left ventricle developed pressure, dP/dt max, and fractional shortening were significantly decreased (P <.001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P <.001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P <.001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P <.01 each vs VEH). Mitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT. [Display omitted] [ABSTRACT FROM AUTHOR]

Duplex stainless steels (DSS) are defined by their equal phase composition of ferrite and austenite. However, the in-situ formation of this duplex microstructure in laser-based additive manufacturing (AM) is still a challenging topic. Nanoparticle addition is a promising approach to tailor the microstructure of steels in AM. Therefore, DSS doped with 0.5 wt.-% NiO nanoparticles was fabricated by laser-based powder bed fusion (PBF-LB) and directed energy deposition (DED-LB). While having no impact on the phase composition in PBF-LB, the addition of NiO nanoparticles showed a significant increase in austenite content of 9% compared to the unmodified powder in DED-LB. [ABSTRACT FROM AUTHOR]

Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0–2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%–77%) and was lower (35%) against Omicron infection (95% CI 21%–47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0–2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%–75%) 3–6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring. [ABSTRACT FROM AUTHOR]

Educational Aims • Summarise the clinical trials involving the four currently available CFTR modulators. • Highlight pulmonary and extra-pulmonary benefits of CFTR modulator therapies. • List known adverse events associated with CFTR modulator therapies. Highly effective modulator therapies (HEMTs) have revolutionised the management approach of most patients living with cystic fibrosis (CF) who have access to these therapies. Clinical trials have reported significant improvements across multiorgan systems, with patients surviving longer. However, there are accumulating case reports and observational data describing various adverse events following initiation of HEMTs including drug-to-drug interactions, drug induced liver injury, Stevens-Johnson syndrome, and neurocognitive symptoms including psychosis and depression, which have required discontinuation of therapy. Current clinical trials are assessing efficacy in younger patients with CF, yet long-term studies are also required to better understand the safety profile in the real-world setting across all ages and the impact of HEMT dose alteration or discontinuation. [ABSTRACT FROM AUTHOR]

The reader will be able to • Identify the classification of cough medications. • Understand the limited data supporting the use of cough medications in children. • Recognize the risks and adverse effects attributed to cough medication use. Cough medicines have been in use for over a century to treat the common and troublesome, but often helpful, symptoms of cough in children. They contain various combinations of "anti-tussive" drugs including opioids, antihistamines, herbal preparations, mucolytics, decongestants and expectorants. Whilst theoretically attractive for symptom relief when children are suffering, as time has passed these popular over the counter medicines have been shown to lack efficacy, delay more serious underlying diagnoses, and can cause complications and sometimes death. This has resulted in clinician concerns, a citizen petition to the American Food and Drug Association in 2007, some self-regulation from manufacturers and escalating restrictions on their use from regulatory agencies across the world over the last twenty years. This article will review the protective role of cough, juxtapose the conflicting treatment goals of suppressing a dry cough and promoting expectoration for a wet cough, consider the evidence basis for prescribing cough medicines in comparison to other more specific treatments such as for asthma [beta agonists] or infection [antibiotics], regulatory interventions, and conclude with the view that over counter cough medicines should not be used in children, especially young children. [ABSTRACT FROM AUTHOR]

Educational Aims • The current published research on the use of bacteriophages for the treatment of P. aeruginosa and/or S. aureus. • The variety of treatment regimens employed for patients undergoing bacteriophage therapy under compassionate access. • The outcomes of bacteriophage treatment in cystic fibrosis patients with lung infections caused by P. aeruginosa and/or S. aureus. Respiratory infections caused by Staphylococcus aureus and Pseudomonas aeruginosa are a major concern for cystic fibrosis (CF) patients due to increasing antibiotic resistance. Bacteriophages, which are viruses that selectively target and kill bacteria, are being studied as an alternative treatment for these infections. This systematic review evaluates the safety and effectiveness of bacteriophages for the treatment of CF-related infections caused by S. aureus and/or P. aeruginosa. We conducted a search for original, published articles in the English language up to March 2023. Studies that administered bacteriophages via intravenous, nebulised, inhaled, or intranasal routes were included, with no comparators required. In vitro and in vivo studies were eligible for inclusion, and only animal in vivo studies that utilised a CF transmembrane conductance regulator (CFTR) animal model were included. Bacteriophage treatment resulted in a decrease in bacterial load in both humans and animals infected with P. aeruginosa. Complete eradication of P. aeruginosa was only observed in one human subject. Additionally, there was a reduction in biofilm, improvement in resistance profile, and reduced pulmonary exacerbations in individual case reports. Evidence suggests that bacteriophage therapy may be a promising treatment option for CF-related infections caused by P. aeruginosa and S. aureus. However, larger and more robust trials are needed to establish its safety and efficacy and create necessary evidence for global legislative frameworks. [ABSTRACT FROM AUTHOR]

The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString n Counter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time. Eighty-two subjects (50% female, median age 54 years (range 3–73)) with COVID-19 were recruited. Paired URT viral load samples were available for 16 blood transcriptome samples, and 17 respiratory epithelial transcriptome samples. Natural Killer (NK) cells were the only blood cell type significantly correlated with URT viral load z-scores (r = −0.62, P = 0.010). Twenty-four blood gene expression modules were significantly correlated with URT viral load z-score, the most significant being a module of genes connected around IFNA14 (Interferon Alpha-14) expression (r = −0.60, P = 1e-10). In fixed repertoire analysis, prostanoid-related gene expression was significantly associated with higher viral load. In nasal epithelium, only GNLY (granulysin) gene expression showed significant negative correlation with viral load. Correlations between the transcriptional host response and inter-individual variations in SARS-CoV-2 URT viral load, revealed many molecular mechanisms plausibly favouring or constraining viral replication. Existing evidence corroborates many of these mechanisms, including likely roles for NK cells, granulysin, prostanoids and interferon alpha-14. Inhibition of prostanoid production and administration of interferon alpha-14 may be attractive transmission-blocking interventions. [Display omitted] • SARS-CoV-2 upper respiratory viral z-scores were correlated with host response. • Negative correlation between viral load and blood NK cells and IFN-α14 module. • Positive correlation between blood prostanoid module and viral load. • Nasal granulysin expression negatively correlated with viral load z-score. • Identifies putative mechanisms favouring and restricting SARS-CoV-2 replication. [ABSTRACT FROM AUTHOR]

The use of fascicle transfers in the reconstruction of traumatic brachial plexus injury is well established, but limited evidence is available regarding their use in atraumatic elbow flexion paralysis. This retrospective case review aimed to verify whether median and ulnar fascicle transfers are similarly effective in atraumatic versus traumatic elbow flexion paralysis when measured using the British Medical Research Council (MRC) scale, Brachial plexus Assessment Tool (BrAT) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) scores at long-term follow-up. All median and ulnar fascicle transfer cases performed at the Queen Elizabeth Hospital Birmingham between August 2007 and November 2018 were reviewed to compare the outcomes of transfers performed for traumatic and atraumatic indications. Data on patient demographics, mechanism and nature of injury, date of injury or symptom onset, date of operation, and other nerve transfers performed were collected. Outcome measures collected included the British MRC scale and two patient-reported outcome measures (PROMs), BrAT and SPONEA. In total, 34 patients with 45 median and ulnar fascicle transfers were identified. This included 27 traumatic and seven atraumatic brachial plexus insults. Thirty patients had sufficient follow-up to be included in MRC analysis and 17 patients had sufficient follow-up to be included in PROM analysis. No significant differences were found between traumatic and atraumatic subgroups for median MRC, BrAT, or SPONEA scores. This study suggests that nerve transfers might be considered effective reconstructive options in atraumatic pathology and provides validation for further research on the subject. [ABSTRACT FROM AUTHOR]

In October 2018, the United States implemented a change in the donor heart allocation policy from a three-tiered to a six-tiered status system. The purpose of the current study was to examine changes in waitlist patterns among patients listed for concomitant heart-liver transplantation with implementation of the new allocation system. Patients listed for heart-liver transplantation between January 1, 2012, and June 30, 2021, were identified from the United Network for Organ Sharing database. Patients were grouped by era according to initial list date before or after October 18, 2018. Competing risks regression for mortality, transplantation, removal from waitlist due to illness was performed according to the method of Fine and Gray. Waitlist data were censored at 3 years from initial listing. Overall, 523 patients were identified, of whom 310 were listed before (era 1, 59%) and 213 after (era 2, 41%) allocation change. Patients in era 1 were older, had more restrictive cardiomyopathy, and more preoperative inotrope use (all P <.05). However, patients in era 2 has longer ischemic times (3.5 ± 1.1 vs 3.1 ± 1.1 hours, P <.01) and more intraaortic balloon pump use (8.9% vs 3.9%, P =.016). Era 2 was associated with lower subdistribution hazard for death (hazard ratio 0.37; 95% CI, 0.13-1.02; P =.054) and increased transplantation (hazard ratio 1.35; 95% CI, 1.06-1.72; P =.015). The implementation of the US donor heart allocation policy was associated with more preoperative intraaortic balloon pump use for patients listed for heart-liver transplantation. Despite that, the modern era was associated with lower waitlist mortality and more frequent transplantation, without increased risk of delisting due to illness. [ABSTRACT FROM AUTHOR]

Left atrial appendage occlusion (LAAO) is an approved alternative for stroke prevention in atrial fibrillation for patients with an "appropriate rationale" to avoid long-term oral anticoagulation (OAC). Many patients undergoing LAAO are at high risk of bleeding. This study sought to investigate whether dual antiplatelet therapy (DAPT) is a safe alternative to OAC (direct oral anticoagulation [DOAC] or warfarin) with aspirin after LAAO. Using National Cardiovascular Data Registry LAAO registry data, patients undergoing Watchman FLX (Boston Scientific) implantation (August 5, 2020-September 30, 2021) were included in 1:1 propensity-matched analyses comparing discharge medication regimens (DAPT, DOAC/aspirin, or warfarin/aspirin). A composite endpoint (death, stroke, major bleeding, and systemic embolism), its components, and device-related thrombus between discharge and 45 days were evaluated. In 49,968 patients implanted with the Watchman FLX during the study period, the mean age was 77 years, and 40% were women. Postimplant DOAC/aspirin was prescribed in 24,497 patients, warfarin/aspirin in 3,913, and DAPT in 4,155. DAPT patients had more comorbid conditions than patients receiving OAC/aspirin. After propensity score matching, the 45-day composite endpoint rates were similar among the groups (DAPT = 3.44% vs DOAC/aspirin: 4.06%; P = 0.13 and DAPT = 3.23% vs warfarin/aspirin: 3.08%; P = 0.75). Death, stroke, and device-related thrombus were also similar; major bleeding was slightly increased in DOAC/aspirin patients (DAPT = 2.48% vs DOAC/aspirin = 3.25%; P = 0.04 and DAPT = 2.25% vs warfarin/aspirin = 2.22%; P = 0.93). In a large registry, DAPT had a similar safety profile compared with current Food and Drug Administration–approved postimplant drug regimens of OAC with aspirin following LAAO with the Watchman FLX. Shared decision making for nonpharmacologic stroke prevention should include a discussion of postprocedure medical therapy options. [Display omitted] [ABSTRACT FROM AUTHOR]

The RASA2 and RASA3 GTPase-activating proteins are recently recognized negative regulators of T cell activation and adhesion. RASA2 was identified as a novel immunotherapy target in a CRISPR-Cas9 screen for molecules permitting human primary T cell proliferation in the presence of inhibitors. RASA2 depletion increased antigen sensitivity in conventional and chimeric antigen receptor (CAR)-T cells and improved tumor rejection. RASA3 was identified in a CRISPR-Cas9 screen as an inhibitor of T cell receptor (TCR)-induced LFA-1-mediated ICAM-1 binding in mouse T cells. Rasa3 deficiency altered T cell adhesion, migration, and T cell-dependent antibody responses in mice. Rasa3 is highly expressed in pathogenic type 17 T helper cells and is required for the development of experimental autoimmune encephalitis in mice, suggesting that it has T cell type- and tissue-specific functions. Both RASA2/Rasa2 and RASA3/Rasa3 are rapidly repressed upon TCR stimulation of human and mouse T cells, thus promoting T cell activation. RASA3 is also inhibited by PI3K activity. Understanding the mechanisms that keep T cells in check can provide insight into targets for reinvigorating T cell function in cancer and chronic infection, or for suppressing T cell function in the context of autoimmunity and transplantation. The RASA2 and RASA3 GAPs have recently emerged as key inhibitors of T cell activation, adhesion, and migration, thereby introducing a potential new set of therapeutic targets for manipulating T cell activity. Following stimulation, the T cell receptor (TCR) and its coreceptors integrate multiple intracellular signals to initiate T cell proliferation, migration, gene expression, and metabolism. Among these signaling molecules are the small GTPases RAS and RAP1, which induce MAPK pathways and cellular adhesion to activate downstream effector functions. Although many studies have helped to elucidate the signaling intermediates that mediate T cell activation, the molecules and pathways that keep naive T cells in check are less understood. Several recent studies provide evidence that RASA2 and RASA3, which are GAP1-family GTPase-activating proteins (GAPs) that inactivate RAS and RAP1, respectively, are crucial molecules that limit T cell activation and adhesion. In this review we describe recent data on the roles of RASA2 and RASA3 as gatekeepers of T cell activation and migration. [ABSTRACT FROM AUTHOR]