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Meniscus repair has increased in frequency, especially among surgeons who focus on youth sports injuries. The aim of this study was to determine current trends in meniscus repair among a specific subset of meniscus repair surgeons. A cross-sectional survey utilizing several clinical vignettes was administered to orthopaedic surgeon members of the Pediatric Research in Sports Medicine (PRiSM) Society to investigate surgeon experience and training, number of meniscus repair procedures performed, and surgical and rehabilitation preferences. A statistical analysis of the responses was performed to determine associations between years in practice or type of fellowship training and the number of meniscus repair procedures performed, surgical indications, and rehabilitation preferences. The response rate to various questions ranged from 61.5 (59/96) to 63.5% (61/96). In all vignettes, a majority favored repair as well as some degree of weight-bearing and range-of-motion restrictions. Surgeons who had been in practice for 6 to 10 years performed significantly more meniscus repairs per year than those who had been in practice for greater than 20 years ( p  = 0.009) and those who had been in practice for 0 to 5 years ( p  = 0.05). Surgeons who had been in practice for greater than 20 years performed a significantly higher percentage of meniscectomies relative to meniscus repairs, compared with those in practice for 0 to 5 years ( p  = 0.002) or 6 to 10 years ( p  = 0.0003). When surgeons were grouped into those with less than 10 years of experience and those with greater than 10 years of experience, the former group performed a significantly higher number of meniscus repairs relative to meniscectomies than the latter group of surgeons ( p  < 0.0001). Less experienced surgeons are more likely to perform meniscus repair than meniscectomy, but all surgeons surveyed had a general preference for repair in all clinical vignettes. Repair technique preferences as well as rehabilitation protocols varied widely among surgeons., Competing Interests: None declared., (Thieme. All rights reserved.)

Hepatitis E virus (HEV) variants infecting humans belong to two species: Paslahepevirus balayani (bHEV) and Rocahepevirus ratti (rat hepatitis E virus; rHEV). R. ratti is a ubiquitous rodent pathogen that has recently been recognized to cause hepatitis in humans. Transmission routes of rHEV from rats to humans are currently unknown. In this study, we examined rHEV exposure in cats and dogs to determine if they are potential reservoirs of this emerging human pathogen. Virus-like particle-based IgG enzymatic immunoassays (EIAs) capable of differentiating rHEV & bHEV antibody profiles and rHEV-specific real-time RT-PCR assays were used for this purpose. The EIAs could detect bHEV and rHEV patient-derived IgG spiked in dog and cat sera. Sera from 751 companion dogs and 130 companion cats in Hong Kong were tested with these IgG enzymatic immunoassays (EIAs). Overall, 13/751 (1.7%) dogs and 5/130 (3.8%) cats were sero-reactive to HEV. 9/751 (1.2%) dogs and 2/130 (1.5%) cats tested positive for rHEV IgG, which was further confirmed by rHEV immunoblots. Most rHEV-seropositive animals were from areas in or adjacent to districts reporting human rHEV infection. Neither 881 companion animals nor 652 stray animals carried rHEV RNA in serum or rectal swabs. Therefore, we could not confirm a role for cats and dogs in transmitting rHEV to humans. Further work is required to understand the reasons for low-level seropositivity in these animals.

Tsukamurella , a group of multi-drug resistant, Gram-positive, aerobic, and partially acid-fast bacteria, are emerging causes of bacterial conjunctivitis and keratitis. However, the pathogenesis of Tsukamurella keratitis is largely unknown. To address this, we used New Zealand White rabbits to develop the first eye infection model and conducted in vitro tests to study the pathogenesis mechanisms of Tsukamurella . There is increasing evidence that biofilms play a significant role in ocular infections, leading us to hypothesize that biofilm formation is crucial for effective Tsukamurella infection. In order to look for potential candidate genes which are important in biofilm formation and Tsukamurella keratitis. We performed genome sequencing of two ocular isolates, T. pulmonis -PW1004 and T. tyrosinosolvens -PW899, to identify potential virulence factors. Through in vitro and in vivo studies, we characterized their biological roles in mediating Tsukamurella keratitis. Our findings confirmed that Tsukamurella is an ocular pathogen by fulfilling Koch's postulates, and using genome sequence data, we identified tmytC, encoding a mycolyltransferase, as a crucial gene in biofilm formation and causing Tsukamurella keratitis in the rabbit model. This is the first report demonstrating the novel role of mycolyltransferase in causing ocular infections. Overall, our findings contribute to a better understanding of Tsukamurella pathogenesis and provide a potential target for treatment. Specific inhibitors targeting TmytC could serve as an effective treatment option for Tsukamurella infections.

Klebsiella pneumoniae is a ubiquitous opportunistic pathogen of the family Enterobacteriaceae. K. pneumoniae is a member of the ESKAPEE pathogens ( Enterococcus faecium, Staphylococcus aureus, K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli ), a group of bacteria that cause nosocomial infections and are able to resist killing by commonly relied upon antimicrobial agents. The acquisition of antimicrobial resistance (AMR) genes is increasing among community and clinical isolates of K. pneumoniae, making K. pneumoniae a rising threat to human health. In addition to the increase in AMR, K. pneumoniae is also thought to disseminate AMR genes to other bacterial species. In this review, the known mechanisms of K. pneumoniae AMR will be described and the current state of AMR K. pneumoniae within Canada will be discussed, including the impact of the coronavirus disease-2019 pandemic, current perspectives, and outlook for the future., Competing Interests: The authors declare there are no competing interests.

Background: Medical treatment for Crohn's disease (CD) has continuously improved, which has led to a decrease in surgical recurrence rates. Despite these advancements, 25% of patients will undergo repeat intestinal surgery. Recurrence of CD commonly occurs on the mesentery side of the anastomosis site., Aim: To compare the new anti-mesenteric side-to-side delta-shaped stapled anastomosis (DSA) with the conventional stapled functional end-to-end anastomosis (CSA)., Methods: This retrospective study included CD patients who underwent ileo-ileal or ileo-colic anastomosis between January 2020 and December 2023. The DSA technique employed a stapler to maintain the concept of anti-mesentery side-to-side anastomosis by performing a 90° vertical closure of the open window compared with the CSA technique. At the corner where the open window is closed, the DSA avoids forming a pouch and creates an anastomosis resembling a delta shape within the intestinal lumen. We compared demographics, preoperative condition, operative findings, and operative outcomes for the two techniques., Results: The study included 175 patients, including 92 in the DSA group and 83 in the CSA group. The two groups were similar in baseline characteristics, preoperative medical treatment, and operative findings except for the Montreal classification location. The 30-days postoperative complication rate was significantly lower in the DSA group compared with the CSA group (16.3% vs 32.5%, P = 0.009). Ileus incidence was significantly lower in the DSA group than in the CSA group (4.3% vs 14.5%, P = 0.033), and the hospital stay was shorter in the DSA group than in the CSA group (5.67 ± 1.53 days vs 7.39 ± 3.68 days, P = 0.001)., Conclusion: The DSA technique was feasible and showed comparable postoperative outcomes with lower short-term complications compared with the CSA technique. Further studies on CD recurrence and long-term complications are warranted., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Positive associations between levels of socioeconomic inequality and homicide rates have been reported at various geographical levels (e.g., between countries, states, cities, and neighborhoods within a city). However, the extent to which inequality predicts levels of non-lethal violence has been less frequently studied. The present study was conducted to investigate the association between socioeconomic inequality and levels of non-lethal interpersonal violence across neighborhoods of London during the period 2010 to 2012, using two independent data sources: Metropolitan Police service recorded violent crime and London Ambulance Service recorded assaults. Mean income per person and local life expectancy were included as additional predictors. Following exclusions due to census boundary changes, across 533 London wards, there were positive bivariate associations between both violence measures and a measure of inequality between neighborhoods (census lower layer super output areas [LSOAs]) within a ward. Moreover, there were negative bivariate associations between violence rates and both ward mean income and life expectancy measures for males and females. However, in a regression analysis only inequality and male life expectancy were consistent predictors of rates of interpersonal violence across outcome measures. The results of the present study provide further evidence of an association between levels of economic inequality and rates of interpersonal violence. The findings, for variation in rates of non-lethal violence across small geographical areas (neighborhoods), build on previous research that has mostly focused on rates of lethal violence and has tended to use aggregate measures across larger geographical areas., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies., Methods: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response)., Results: A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P = 0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P = 0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively., Conclusions: Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.)., (Copyright © 2024 Massachusetts Medical Society.)

Background and Objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy., Methods: Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m 2 ], docetaxel [75 mg/m 2 ], or vinflunine [320 mg/m 2 ], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response., Key Findings and Limitations: An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing., Conclusions and Clinical Implications: When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC., (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The Royal Australasian College of Surgeons (RACS) recently instituted cultural safety and cultural competency as its 10th competency with formalized cultural safety training yet to be instituted. Wānanga are Indigenous Māori teaching institutions that can be used contemporarily for cultural safety training., Methods: In 2022, surgical registrars based at Taranaki Base Hospital (TBH) held in-hospital wānanga ranging from 1 to 3 h focussed on cultural safety, professionalism and wellbeing. This study explores the perspectives of these registrars who attended wānanga using a Kaupapa Māori aligned methodological stance and interpretive phenomenological analysis., Results: Twenty-six wānanga were held from March 22nd 2022 to January 30th 2023. Six registrars provided their perspectives with four major themes emerging from their stories including: cultural safety; unity; time, place and person; and a new era. Registrars valued the wānanga which was scheduled for Friday afternoons after daily clinical duties. Wānanga facilitated unity and understanding with registrars being able to reflect on the context within which they are practicing - describing it as a new era of surgical training. 'Time' was the biggest barrier to attend wānanga however, the number of wānanga held was testament to the commitment of the registrars., Conclusions: Regular wānanga set up by, and for, surgical registrars cultural safety development is feasible and well subscribed in a rural or provincial NZ setting. We present one coalface method of regular cultural safety training and development for surgical registrars and trainees in NZ., (© 2024 The Author(s). ANZ Journal of Surgery published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Surgeons.)

The global prevalence rate for congenital hydrocephalus (CH) is approximately one out of every five hundred births with multifaceted predisposing factors at play. Genetic influences stand as a major contributor to CH pathogenesis, and epidemiological evidence suggests their involvement in up to 40% of all cases observed globally. Knowledge about an individual's genetic susceptibility can significantly improve prognostic precision while aiding clinical decision-making processes. However, the precise genetic etiology has only been pinpointed in fewer than 5% of human instances. More occurrences of CH cases are required for comprehensive gene sequencing aimed at uncovering additional potential genetic loci. A deeper comprehension of its underlying genetics may offer invaluable insights into the molecular and cellular basis of this brain disorder. This review provides a summary of pertinent genes identified through gene sequencing technologies in humans, in addition to the 4 genes currently associated with CH (two X-linked genes L1CAM and AP1S2, two autosomal recessive MPDZ and CCDC88C). Others predominantly participate in aqueduct abnormalities, ciliary movement, and nervous system development. The prospective CH-related genes revealed through animal model gene-editing techniques are further outlined, focusing mainly on 4 pathways, namely cilia synthesis and movement, ion channels and transportation, Reissner's fiber (RF) synthesis, cell apoptosis, and neurogenesis. Notably, the proper functioning of motile cilia provides significant impulsion for cerebrospinal fluid (CSF) circulation within the brain ventricles while mutations in cilia-related genes constitute a primary cause underlying this condition. So far, only a limited number of CH-associated genes have been identified in humans. The integration of genotype and phenotype for disease diagnosis represents a new trend in the medical field. Animal models provide insights into the pathogenesis of CH and contribute to our understanding of its association with related complications, such as renal cysts, scoliosis, and cardiomyopathy, as these genes may also play a role in the development of these diseases. Genes discovered in animals present potential targets for new treatments but require further validation through future human studies., (© 2024. The Author(s).)

In low- and middle-income countries where SARS-CoV-2 testing is limited, seroprevalence studies can help describe and characterise the extent of the pandemic, as well as elucidate protection conferred by prior exposure. We conducted repeated cross-sectional serosurveys (July 2020 -November 2021) using residual samples from patients from Cape Town, South Africa, sent for routine laboratory studies for non-COVID-19 conditions. SARS-CoV-2 anti-nucleocapsid antibodies and linked clinical information were used to investigate: (1) seroprevalence over time and risk factors associated with seropositivity, (2) ecological comparison of seroprevalence between subdistricts, (3) case ascertainment rates, and (4) the relative protection against COVID-19 associated with seropositivity and vaccination statuses. Among the subset sampled, seroprevalence of SARS-CoV-2 in Cape Town increased from 39.19% (95% confidence interval [CI] 37.23-41.19) in July 2020 to 67.8% (95%CI 66.31-69.25) in November 2021. Poorer communities had both higher seroprevalence and COVID-19 mortality. Only 10% of seropositive individuals had a recorded positive SARS-CoV-2 test. Using COVID-19 hospital admission and death data at the Provincial Health Data Centre, antibody positivity before the start of the Omicron BA.1 wave (28 November 2021) was strongly protective for severe disease (adjusted odds ratio [aOR] 0.15; 95%CI 0.05-0.46), with additional benefit in those who were also vaccinated (aOR 0.07, 95%CI 0.01-0.35). The high population seroprevalence in Cape Town was attained at the cost of substantial COVID-19 mortality. At the individual level, seropositivity was highly protective against subsequent infections and severe COVID-19 disease. In low-income communities, where diagnostic testing capacity is often limited, surveillance systems dependent on them will underestimate the true extent of an outbreak. Rapidly conducted seroprevalence studies can play an important role in addressing this., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hussey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Penicillin-associated exanthems in the setting of infectious mononucleosis caused by Epstein-Barr virus (EBV) are often viewed as a transient event, not a true allergy. Recent evidence challenges this and suggests that a notable subset of patients retain penicillin hypersensitivity., Objective: We investigated the occurrence and predictors of persistent adulthood hypersensitivity in those with penicillin-associated rash occurring in the setting of EBV infection., Methods: Retrospective analysis of data of patients referred for penicillin allergy testing to an Australian tertiary-care hospital captured from 2015 to 2023 was carried out., Results: Of 2066 patients, 23 (1%) had penicillin-associated rash during an historic EBV infection; 16 (70%) were female; and median (interquartile range) age was 18 (16-20) years at index reaction and 38 (33.5-57) years at allergy testing. Skin prick testing and delayed intradermal testing to a penicillin panel were performed, followed by oral provocation challenge in those testing negative. Persistent sensitization was shown in 6 (26%) of 23; 4 (67%) of 6 positive delayed intradermal testing; and 3 (50%) of 6 had positive oral challenge test. Notably, 5 (83%) of 6 had a severe maculopapular exanthem with facial swelling, including 2 (33%) of 6 with probable drug reaction with eosinophilia and systemic symptoms (aka DRESS) during the index reaction, compared to 0 of 17 in patients tolerating penicillin on reexposure., Conclusion: This study highlights the requirement of allergy testing in adult patients reporting a penicillin-associated severe maculopapular exanthem in the setting of EBV, even if it occurred during childhood or adolescence., Competing Interests: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Objectives: This study aimed to investigate the risk of osteoarthritis associated with menopausal hormone therapy (MHT)., Methods: This population-based retrospective cohort study used a database of Korean health insurance claims (2007-2020). Females aged ≥ 40 who initiated menopause-related healthcare visits between 2011 and 2014 were identified. The MHT group comprised females aged ≥ 40 who initiated MHT for ≥ 6 months during this period. The non-MHT group comprised females aged ≥ 40 who attended menopause-related healthcare visits but did not receive MHT. To account for potential confounding factors, the two groups were matched at a 1:1 ratio using propensity score matching., Results: A cohort of 453,040 postmenopausal females aged ≥ 40 years was identified, with 26,354 assigned to either the MHT or non-MHT group after propensity matching. The median age was 49 years, and the median follow-up was 8.2 years. The Cox proportional hazards model demonstrated an elevated risk of osteoarthritis with MHT (hazard ratio [HR], 1.154; 95% confidence interval [CI], 1.117-1.193) for knee (HR, 1.148; 95% CI, 1.102-1.195) and other arthritis (HR, 1.205; 95% CI, 1.151-1.261), although not statistically significant for hip arthritis. Tibolone (HR, 1.211; 95% CI, 1.161-1.263), estrogen-progestogen therapy (EPT) (HR, 1.092; 95% CI, 1.048-1.137), and estrogen therapy (ET) (HR, 1.235; 95% CI, 1.148-1.329) were associated with a higher risk of osteoarthritis compared to non-MHT users., Conclusions: MHT was associated with an increased risk of osteoarthritis, consistently observed across tibolone, EPT, and ET, particularly affecting joints other than the hip, with a trend toward an elevated risk of hip osteoarthritis., (Copyright © by The Korean Society of Menopause.)

Background: Bronchiolitis accounts for a considerable number of Emergency Department (ED) visits by infants each year and is the leading cause of respiratory infection in children 2 years of age and younger. Suctioning remains one of the main supportive treatments, but suctioning practices of nasal aspiration and deep suctioning vary among practitioners in bronchiolitis management. Our objective was to explore associations between suction type and respiratory distress, oxygen saturation, and markers of respiratory compromise such as airway escalation, disposition, ED length of stay (LOS), and outpatient outcomes., Methods: This was a prospective observational study on infants (aged 2-23 months) in a pediatric ED with bronchiolitis from September 2022 to April 2023. Infants with tracheostomies, muscular weakness, and non-invasive positive pressure ventilation were excluded. Infants were grouped into nasal aspiration, deep suctioning, or combination groups. Mean differences in respiratory scores (primary outcome) and oxygen saturation were measured at three timepoints: pre-suction, 30 and 60 min post-suction. Escalation to airway adjuncts, disposition, and ED LOS were also recorded. Discharged families were contacted for phone call interviews., Results: Of 121 enrolled infants (nasal aspiration n = 31, deep suctioning n = 68, combination n = 22), 48% (n = 58) were discharged, and 90% (n = 52) completed the study call. There was no interaction between suction type and timepoint (p = 0.63) and no effect between suction type and respiratory score (p = 0.38). However, timepoint did have an effect on respiratory score between 0 and 30 min post-suction (p = 0.01) and between 0 and 60 min post-suction (p < 0.001). Admitted infants received more deep suctioning or a combination of suctioning compared to those discharged (p = 0.005). Suction type had no effect on oxygen saturation, airway adjunct escalation, length of stay, or outpatient outcomes (p > 0.11)., Conclusions: There was no difference in respiratory scores or outpatient outcomes between suction types. Deep suctioning may not be needed in all infants with bronchiolitis., Competing Interests: Declaration of competing Interest The authors have indicated they have no conflicts of interest or financial relationships relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Following the emergence of COVID-19, multiple preventative measures were implemented to limit the spread of the disease. This study aims to elucidate the impact of COVID-19 restrictions on hospital admissions of otolaryngology-related infections., Materials and Methods: A retrospective chart review was conducted to capture all admissions for otolaryngology-related infections in the 2 years pre- and post-COVID-19 at the Health Sciences Centre in Winnipeg, Manitoba. These infections included croup, tracheitis, neck abscess, peritonsillar abscess, otitis media, mastoiditis, sinus infection, orbital infection, pharyngotonsillitis, retro/parapharyngeal abscess, and acute epiglottitis. Demographic information and admission details were collected and analyzed to compare pre- and post-COVID-19 admissions. Further analysis was conducted to compare hospital admissions of patients from rural/remote regions., Results: Between March 2018 and March 2022, 253 pediatric patients and 197 adults were admitted for otolaryngology-related infections. Total pediatric admissions decreased post-COVID-19 (154 pre-COVID-19, 99 post-COVID-19; p < 0.001) whereas adult admissions remained stable (107 pre-COVID-19, 90 post-COVID-19; p = 0.25). No significant difference in mean patient age, admission duration, surgical rates or in the proportion of admissions from patients from rural/remote regions was observed in the pediatric or adult cohort when comparing pre-COVID-19 data to post-COVID-19 data. Diagnosis-specific changes in admissions were observed in pediatric croup (40 pre-COVID-19, 15 post-COVID-19; p < 0.001) and in adult orbital infections (30 pre-COVID-19, six post-COVID-19; p < 0.001)., Conclusion: Following the implementation of COVID-19 restrictions, there was a decrease in admissions due to pediatric croup and adult orbital infections with an overall decrease in pediatric Otolaryngology-infection related admissions., Level of Evidence: 3 Laryngoscope, 134:3542-3547, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Glucagon-like Peptide 1 Receptor Agonists (GLP-1 RAs) are a group of relatively novel medications for the treatment of diabetes mellitus. These medications can mimic the naturally occurring incretins of the body, which promote the release of insulin in response to hyperglycaemia. The anti-glycaemic effects of these medications can be profound and carry other metabolic benefits such as promoting weight loss. Clinical trials have shown GLP-1 RAs are safe to use from a cardiovascular perspective. However, some trials have suggested a link between GLP-1 RA use and worsening diabetic retinopathy. The conclusions surrounding this link are poorly established as data is drawn primarily from cardiovascular outcome trials. If an association does exist, a possible explanation might be the observed phenomenon of early worsening diabetic retinopathy with rapid correction of hyperglycaemic states. Trials which look at diabetic retinopathy as a primary outcome in relation to use of GLP-1 RAs are sparse and warrant investigation given the growing use of this group of medications. Therefore currently, it is uncertain what effect, beneficial or adverse, GLP-1 RA use has on diabetic retinopathy. This article provides an overview of GLP-1 RA use as a treatment for diabetes mellitus and the current understanding of their relationship with diabetic retinopathy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The lifetime risk of mental health disorders is almost 50% and, in any year, about 25% of the population have a psychiatric disorder. Many of those people are cared for in primary care settings., Research Objective: Measure access to mental health services, such as getting counselling or prescription mental health medications, using new patient survey questions that can be added to Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys., Study Design: Surveys were conducted with a stratified probability sample of patients receiving primary care services in a single state in 2018-2019. Medicaid and privately insured patients were surveyed by mail or telephone, respectively., Results: Approximately 14% of sampled patients responded to a survey. More than 10% of privately insured respondents and about 20% of Medicaid respondents got or tried to get appointments for mental health care. About 15% of privately insured respondents and 11% of Medicaid respondents reported problems getting appointments with counselors. Only 8%-9% of respondents seeking mental health medicines reported problems getting appointments for prescriptions. A composite measure combining access to counselors and prescribers of mental health medicines evidenced adequate internal consistency reliability. Group level reliability estimates were low., Conclusions: Many respondents got or tried to get mental health services and a substantial number reported problems getting appointments or getting mental health prescriptions. The tested questions can be combined into an Access to Mental Health Care measure, which can be included in patient experience surveys for ambulatory care to monitor access to behavioral health care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

To contribute to our understanding of cohort differences and the Flynn effect in the cognitive decline among older Americans, this study aims to compare rates of cognitive decline between two birth cohorts within a study of older Americans and to examine the importance of medical and demographic confounders. Analyses used data from the National Health and Aging Trends Study (2011-2019), which recruited older Americans in 2011 and again in 2015 who were then followed for 5 years. We employed mixed-effect models to examine the linear and quadratic main and interaction effects of year of birth while adjusting for covariates such as annual round, sex/gender, education, race/ethnicity, heart disease, hypertension, diabetes, test unfamiliarity, and survey design. We analyzed data from 11,167 participants: 7,325 from 2011 to 2015 and 3,842 from 2015 to 2019. The cohort recruited in 2015 was born, on average, 5.33 years later than that recruited in 2011 and had higher functioning than the one recruited in 2011 across all observed cognitive domains that persisted after adjusting for covariates. In multivariable-adjusted analyses, a 1-year increase in year of birth was associated with increased episodic memory (β = 0.045, SE = 0.001, p < .001), orientation (β = 0.034, SE = 0.001, p < .001), and executive function (β = 0.036, SE = 0.001, p < .001). Participants born 1 year later had slower rates of decline in episodic memory (β = 0.004, SE = 0.000, p < .001), orientation (β = 0.003, SE = 0.000, p < .001), and executive function (β = 0.001, SE = 0.000, p = .002). Additionally, sex/gender modified this relationship for episodic memory (-0.007, SE = 0.002, p < .001), orientation (-0.005, SE = 0.002, p = .008), and executive function (-0.008, SE = 0.002, p < .001). These results demonstrate the persistence of the Flynn effect in old age across cognitive domains and identified a deceleration in the rate of cognitive decline across cognitive domains. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Properties of high-entropy alloys are currently in the spotlight due to their promising applications. One of the least investigated aspects is the affinity of these alloys to hydrogen, its diffusion, and reactions. In this study, high pressure is applied at ambient temperature and stress-induced diffusion of hydrogen is investigated into the structure of high-entropy alloys (HEA) including the famous Cantor alloy as well as less known, but nevertheless important platinum group (PGM) alloys. By applying X-ray diffraction to samples loaded into diamond anvil cells, a comparative investigation of transition element incorporating HEA alloys in Ne and H 2 pressure-transmitting media is performed at ambient temperature. Even under stresses far exceeding conventional industrial processes, both Cantor and PGM alloys show exceptional resistance to hydride formation, on par with widely used industrial grade Cu-Be alloys. The observations inspire optimism for practical HEA applications in hydrogen-relevant industry and technology (e.g., coatings, etc), particularly those related to transport and storage., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear., Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD)., Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023., Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2., Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates., Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes., Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive., Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.

Photorechargeable supercapacitors are promising next-generation renewable energy storage devices. Previously, a hybrid structure consisting of indium-tin oxide branched nanowires (ITO BRs) and poly(3-hexylthiophene) (P3HT) was demonstrated as a photorechargeable supercapacitor. However, the formation mechanism of photovoltage has not been studied. Herein, we experimentally investigated the photovoltage-determining parameters in the ITO BRs/P3HT photorechargeable supercapacitor by inserting a polyethylenimine ethoxylated (PEIE) interlayer or adding a phenyl-C61-butyric acid methyl ester (PCBM) electron acceptor. Coating the PEIE interlayer on ITO BRs decreased the work function by 0.5 eV and hindered the hole extraction from P3HT to ITO BRs, leading to interfacial recombination and a decrease in photovoltage. On the other hand, the addition of PCBM promoted the charge transfer of the electrons from P3HT to PCBM, enhanced the redox reaction at the PCBM/electrolyte interface, and reduced the number of accumulated electrons, leading to a decreased photovoltage. From these results, we found that two key parameters determine the photovoltage and charge storage capability; one is the interfacial recombination at the ITO BRs/P3HT interface and the other is the redox reaction at the P3HT/electrolyte interface.

Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC., Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1., Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects., Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab., Clinical Trial Registration: ClinicalTrials.gov; NCT03260894 ., (© 2023. The Author(s).)

In 2021, the National Association of School Nurses published an updated position statement affirming the unique position of school nurses to support the health and well-being of lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) students who are faced with a variety of health disparities rooted in experiences of stigma, discrimination, and bias. The 5-year cluster randomized controlled trial "Reducing LGBTQ+ Adolescent Suicide" leveraged school nurses as leaders to facilitate the uptake of six evidence-informed, LGBTQ-supportive practices in New Mexico high schools. We analyzed 5 years of interview data from 24 school nurses in 13 intervention schools to examine what factors impacted their ability to serve as an effective leader for this initiative. Several factors including job characteristics, leadership and organizational skills, relationships and reputation, and personal commitments emerged from analysis. Contextual factors, such as working in urban or rural school, and the size of the school also influenced nurses' leadership., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Electronic health records (EHRs) can accelerate documentation and may enhance details of notes, or complicate documentation and introduce errors. Comprehensive assessment of documentation quality requires comparing documentation to what transpires during the clinical encounter itself. We assessed outpatient primary care notes and corresponding recorded encounters to determine accuracy, thoroughness, and several additional key measures of documentation quality., Methods: Patients and primary care clinicians across five midwestern primary care clinics of the US Department of Veterans Affairs were recruited into a prospective observational study. Clinical encounters were video-recorded and transcribed verbatim. Using the Physician Documentation Quality Instrument (PDQI-9) added to other measures, reviewers scored quality of the documentation by comparing transcripts to corresponding encounter notes. PDQI-9 items were scored from 1 to 5, with higher scores indicating higher quality., Results: Encounters (N = 49) among 11 clinicians were analyzed. Most issues that patients initiated in discussion were omitted from notes, and nearly half of notes referred to information or observations that could not be verified. Four notes lacked concluding assessments and plans; nine lacked information about when patients should return. Except for thoroughness, PDQI-9 items that were assessed achieved quality scores exceeding 4 of 5 points., Conclusions: Among outpatient primary care electronic records examined, most issues that patients initiated in discussion were absent from notes, and nearly half of notes referred to information or observations absent from transcripts. EHRs may contribute to certain kinds of errors. Approaches to improving documentation should consider the roles of the EHR, patient, and clinician together., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Competing Interests: The authors have declared that no competing interests exist.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients., Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided., Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from 6 available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient., Conclusion: Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Existing barriers to care were exacerbated by the development and implementation of necessary public health restrictions during the COVID-19 pandemic. Children with complex care needs and their families represent a small portion of the paediatric population, and yet they require disproportionately high access to services. Little is known about the impact of COVID-19 public health measures on this population. This study will generate evidence to uncover the wider impact of COVID-19 measures on the lives of children with complex care needs and their families in relation to policy and service changes. This multi-site sequential mixed methods study will take place across the Canadian Maritime provinces and use an integrated knowledge translation approach. There are two phases to this study: 1) map COVID-19 public health restrictions and service changes impacting children with complex care needs by conducting an environmental scan of public health restrictions and service changes between March 2020 and March 2022 and interviewing key informants involved in the development or implementation of restrictions and service changes, and 2) explore how children with complex care needs and their families experienced public health restrictions and service changes to understand how their health and well-being were impacted., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Curran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Anti-citrullinated protein autoantibodies (ACPA) are diagnostic for rheumatoid arthritis (RA). The antigens recognized by these autoantibodies are produced by protein arginine deiminases (PADs), particularly PAD4. However, it remains unknown why and how PAD4 causes this aberrant citrullination in RA. Here, we report that poly-perforin pores are present on freshly isolated neutrophils from RA patients, but not on healthy donor neutrophils. Neutrophils with perforin pores also contained intracellular citrullinated proteins in the region adjacent to the pores. This response was replicated in vitro by treating neutrophils with purified perforin, which generated intense dots of anti-perforin immunofluorescence, calcium influx, and intracellular citrullination. Extensive neutrophil killing in Felty's syndrome, an aggressive form of RA, correlated with particularly high ACPA, and PAD4 autoantibodies. In contrast, other forms of death, including NETosis, apoptosis, and pyroptosis, produced minimal citrullination. We conclude that neutrophil targeting by perforin leading to intracellular citrullination takes place in patients with RA., (© 2024. The Author(s).)

This review aims to highlight the role of silicon in drug discovery. Silicon and carbon are often regarded as being similar with silicon located directly beneath carbon in the same group in the periodic table. That being noted, in many instances a clear dichotomy also exists between silicon and carbon, and these differences often lead to vastly different physiochemical and biological properties. As a result, the utility of silicon in drug discovery has attracted significant attention and has grown rapidly over the past decade. This review showcases some recent advances in synthetic organosilicon chemistry and examples of the ways in which silicon has been employed in the drug-discovery field., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Prenatal drug exposure (PDE) is a global public health problem that is strongly associated with the need for child protection services, including placement into out-of-home care (OOHC). We aimed to assess school outcomes for children with PDE (both with and without neonatal abstinence syndrome [NAS]) and the association of school performance with OOHC., Methods: Using linked population health, OOHC, and school test data, we compared results on the Australian standardised curriculum-based test, the National Assessment Program-Literacy and Numeracy (NAPLAN), for children with PDE who were born in New South Wales (NSW) between 2001 and 2020 and had completed at least one NAPLAN test between Jan 1, 2008, and June 30, 2021, administered in Year 3 (age 8-9 years), Year 5 (age 10-11 years), Year 7 (age 12-13 years), or Year 9 (age 14-15 years). Linked datasets included NSW Perinatal Data Collection (birth data), NSW Admitted Patient Data Collection (hospital diagnoses), NSW Education Standards Authority (NAPLAN scores), NSW Family and Community Services Dataset-KiDS Data Collection (OOHC information), NSW Mental Health Ambulatory Data Collection, and NSW Registry for Births, Deaths, and Marriages. The primary outcome was scoring above or below the National Minimum Standard (NMS) in any test domain (mathematics, language, writing, and spelling) at each year level, comparing the relative risk of scoring below NMS between children with and without PDE (and with or without NAS within the PDE group), and with and without OOHC contact. The association between OOHC on the likelihood of scoring above NMS was also investigated for PDE and non-PDE cohorts., Findings: The PDE cohort included 3836 children, and the non-PDE cohort included 897 487 children. Within the PDE cohort, 3192 children had a NAS diagnosis and 644 children had no NAS diagnosis. 1755 (45·8%) children with PDE required OOHC compared with 12 880 (1·4%) of 897 487 children without PDE. Children with PDE were more likely than children without PDE to score below NMS in any domain from Year 3 (risk ratio 2·72 [95% CI 2·58-2·76]) to Year 9 (2·36 [2·22-2·50]). Performance was similar regardless of a NAS diagnosis (Year 3: 0·96 [0·84-1·10]; Year 9: 0·98 [0·84-1·15]). The likelihood of scoring above NMS in Year 9 was reduced for children with PDE and without NAS (0·57 [0·45-0·73]) and NAS (0·58 [0·52-0·64]) compared with those without PDE, and also for children who received OOHC (0·60 [0·57-0·64]) compared with those without OOHC, when adjusted for confounders. Among children with PDE, those receiving OOHC had a similar likelihood of scoring above NMS compared with children who did not receive OOHC, from Year 3 (1·01 [0·92-1·11]) to Year 9 (0·90 [0·73-1·10]), when adjusted for confounding factors. By contrast, among children without PDE, those receiving OOHC were less likely to score above NMS than those who did not receive OOHC, from Year 3 (0·78 [0·76-0·80]) to Year 9 (0·58 [0·54-0·61])., Interpretation: Compared with children without PDE, school performance in children with PDE-regardless of whether they were diagnosed with NAS-is poor, and the gap widens with age. The risk of poor performance persists regardless of OOHC status. This finding underscores the need for all children with PDE to receive long-term, culturally sensitive, and proactive support to improve life success., Funding: SPHERE Mindgardens Neuroscience Network, Australian Red Cross, Alpha Maxx Healthcare, Centre for Research Excellence for Integrated Health and Social Care, National Health and Medical Research Council, and University of Sydney., Competing Interests: Declaration of interests JLO declares support for research and travel from Mallinkrodt outside this study. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC)., Methods: Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines., Results: Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI., Conclusions: There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan., (© 2024 John Wiley & Sons Australia, Ltd.)

The ways in which drugs are policed, differs from country to country, with Drug Detector Dogs (DDDs) a commonly used detection strategy in Australia. However, their effectiveness has been scrutinized by Australian media and research. Despite this, their work and lives "on the job" continue to be portrayed in a positive light on popular television shows such as Border Security. The aim of the current study was to ascertain public perceptions and knowledge surrounding DDDs using a sample of 129 Australians. Results revealed participants believed DDDs were equally as interesting and as happy as companion dogs. However, while there was general support for both dog roles in human lives, participants were relatively less supportive of the use of DDDs. Importantly, findings suggest general Australians have little awareness of the lives of DDDs "off the job," including housing and handling practices that directly impact animal welfare. We suggest that greater transparency around these aspects of the dogs' lives and welfare experience be made publicly available so that the DDD industry can maintain their social license to operate.

A review from the last seven years (August 2016-July 2023) of questions posted to the International Society for Peritoneal Dialysis (ISPD) website "Questions about PD" by nurses and physicians from around the world revealed that 19 of the questions were associated with optimal approaches for preventing, assessing, and managing issues related to PD catheter non-infectious complications. Our review focused on responses to these questions whereby existing best practice recommendations were considered, if available, relevant literature was cited and differences in international practices discussed. We combined similar questions, revised both the original questions and responses for clarity, as well as updated the references to these questions. PD catheter non-infectious complications can often be prevented or, with early detection, the potential severity of the complication can be minimized. We suggest that the PD nurse is key to educating the patient on PD about PD catheter non-infectious complications, promptly recognize a specific complication and bring that complication to the attention of the Home Dialysis Team. The questions posted to the ISPD website highlight the need for more education and resources for PD nurses worldwide on the important topic of non-infectious complications related to PD catheters, thereby enabling us to prevent such complications as PD catheter malfunction, peri-catheter leakage and infusion or drain pain, as well as recognize and resolve these issues promptly when they do arise, thus allowing patients to extend their time on PD therapy and enhance their quality of life whilst on PD., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [ 68 Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [ 68 Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy., (© 2024. The Author(s).)

Introduction: Due to concerns of oxidative stress and injury, most clinicians currently use lower levels of fractional inspired oxygen (FiO2, 0.21-0.3) to initiate respiratory support for moderate to late preterm (MLPT, 32-36 weeks gestation) infants at birth. Whether this practice achieves recommended oxygen saturation (SpO2) targets is unknown., Methods: We aimed to determine SpO2 trajectories of MLPT infants requiring respiratory support at birth. We conducted a prospective, opportunistic, observational study with consent waiver. Preductal SpO2 readings were obtained during the first 10 min of life from infants between 32 and 36 weeks gestation requiring respiratory support in the delivery room. Primary outcome was reaching a minimum SpO2 80% at 5 min of life. The study was prospectively registered (ACTRN12620001252909)., Results: A total of 76 eligible infants were recruited between February 2021 and March 2022 from 5 hospitals in Australia. Most (n = 58, 76%) had respiratory support initiated with FiO2 0.21 (range 0.21-1.0) using CPAP (92%). Median SpO2 at 5 min was 81% (interquartile range [IQR] 67-90) and 93% (IQR 86-96) at 10 min. At 5 min, 18/43 (42%) infants had SpO2 below 80% and only 8/43 (19%) reached SpO2 80-85%., Conclusions: Many MLPT infants requiring respiratory support do not achieve recommended SpO2 targets. In very preterm infants, SpO2 &lt;80% at 5 min of life increases risk of death, intraventricular haemorrhage, and neurodevelopmental impairment. The implications on this practice on the health outcomes of MLPT infants are unclear and require further research., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Purpose: This study aimed to evaluate the effects of adjuvant chemotherapy (AC) on oncologic outcomes for patients with stage IIA upper rectal cancer and to investigate whether AC is associated with improved survival outcomes., Methods: This retrospective study comprised 432 patients with rectal cancer above the peritoneal reflection who had undergone curative resection without preoperative chemoradiotherapy between 2008 and 2016. This study cohort was divided according to whether AC was received (AC group) or not (no-AC group). Risk factors included obstruction, perforation, poorly-differentiated tumor, lympho-vascular invasion, perineural invasion, resection margin involvement, and < 12 lymph nodes harvested., Results: Among the 432 patients, 279 (64.6%) had received AC. The AC group had significantly higher 5-year overall survival (OS) rates than those of the no-AC group (93.2% vs. 84.6%, P = .001). Among patients with ≥ 1 risk factors, the AC group (n = 123) had significantly higher rates of 5-year recurrence-free survival (RFS) (81.6% vs. 64.1%, P = .01) and 5-year OS (88.8% vs. 69.0%, P = .001) than those of the no-AC group (n = 59). No significant difference in survival outcomes was observed between the 2 groups in patients aged > 65 years., Conclusion: AC was significantly associated with better 5-year RFS and 5-year OS rates in patients with stage IIA rectal cancer above peritoneal reflection who did not receive preoperative chemoradiotherapy, especially in those with ≥ 1 risk factors., Competing Interests: Disclosure The authors have no competing interest to declare that are relevant to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Small interfering RNA (siRNA) is known for its ability to silence the expression of specific genes, demonstrating its promising potential as a therapeutic approach. Self-assembled micelle inhibitory RNA (SAMiRNA) is an oligonucleotide duplex developed to overcome the in vivo delivery limitations of siRNA. SAMiRNA has hydrophilic and hydrophobic groups at both ends of a sense strand, forming a spherical nanostructure that enhances the in vivo delivery efficiency. Ion-pairing reversed-phase liquid chromatography (IP-RPLC) is the most commonly used method for the analysis of oligonucleotides. Since SAMiRNA is heavily chemically modified, the behavior of SAMiRNA in IP-RPLC combined with mass spectrometry (MS) is anticipated to differ from that of the conventional siRNA drug. The current investigation using IP-RPLC-MS revealed that a distinct duplex peak along with two minor separate strands of antisense and sense was observed at column temperatures below 35 °C in the IP-RPLC system with a 100 mM ammonium bicarbonate buffer system. At column temperatures higher than 35 °C, however, two fully denatured single strands were observed. The mass spectrum from the chromatographic peak of the SAMiRNA duplex contained signals from the duplex, the antisense, and the sense, probably due to duplex denaturation during the MS ionization process. The current comprehensive analysis results will make a substantial contribution to the future application of IP-RPLC-MS in the analysis of SAMiRNA.

Background: The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP)., Methods: This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice., Results: Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died., Conclusion: Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies., Competing Interests: SHP has served in consulting or advisory roles for Janssen; reports honoraria from Merck, Ono Pharmaceutical, and Pfizer; and reports research funding from Ono Pharmaceutical and Sanofi. SYR reports advisory roles and speaker services for and has received research funding from Merck. HKS has received research funding from Astellas, AstraZeneca, Basilea, Janssen, Merck, MSD, Ono-BMS, and Roche; and reports consulting, advisory roles, and speaker services for Astellas, Boehringer Ingelheim, Janssen, MSD, Ono-BMS, and Roche. BK has served in advisory roles for ABL Bio, AstraZeneca, CbsBioscience, Cellid, Genexine, Handok, Merck, MSD, and Trial Informatics; reports speaker services from AstraZeneca, Merck, and MSD; and served as coordinating principal investigator for AstraZeneca, MSD, and Ono Pharmaceutical. MK has served in consulting or advisory roles for Eisai, Ipsen, MSD, Ono-BMS, and Yuhan. Y-HH reports employment at Merck Ltd., Seoul, Republic of Korea, an affiliate of Merck KGaA. J-LL reports stock and other ownership interests in Amgen, Black Diamond Therapeutics, Innovent Biologics, Johnson & Johnson/Janssen, Karyopharm Therapeutics, Merck, and Zymeworks; reports honoraria from Astellas, AstraZeneca, BMS, MSD, and Pfizer; has served in consulting or advisory roles for AstraZeneca, BMS, GI Innovation, Merck, MSD, Oscotec, Pfizer, and Sanofi; and has received institutional research funding from Amgen, AstraZeneca/MedImmune, Bayer Schering Pharma, BMS, GI Innovation, Janssen, MSD, Novartis, Pfizer, Roche/Genentech, and Seagen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Merck Ltd. The funder had the following involvement in the study: providing administrative roles for the present study., (Copyright © 2024 Park, Shin, Rha, Beom, Seo, Keam, Kim, Hong, Yoon and Lee.)

The pace at which Next Generation Sequence data is being produced continues to accelerate as technology improves. As a result, such data are increasingly becoming accessible to biologists outside of the field of bioinformatics. In contrast, access to training in the methods of genome assembly and annotation are not growing at a similar rate. In this issue, we report on a Genome Assembly Workshop for Mycologists that was held at the Forestry and Agricultural Biotechnology Institute (FABI) at the University of Pretoria, South Africa and make available the 12 draft genome sequences emanating from the event. With the aim of making the process of genome assembly and annotation more accessible to biologists, we provide a step-by-step guide to both genome assembly and annotation, intended to encourage and empower mycologists to use genome data in their research., (© 2024. The Author(s).)

Background: Myopia affects 1.4 billion individuals worldwide. Notably, there is increasing evidence that choroidal thickness plays an important role in myopia and risk of developing myopia-related conditions. With the advancements in artificial intelligence (AI), choroidal thickness segmentation can now be automated, offering inherent advantages such as better repeatability, reduced grader variability, and less reliance for manpower. Hence, we aimed to evaluate the agreement between AI-automated and manual segmented measurements of subfoveal choroidal thickness (SFCT) using two swept-source optical coherence tomography (OCT) systems., Methods: Subjects aged ≥ 16 years, with myopia of ≥ 0.50 diopters in both eyes, were recruited from the Prospective Myopia Cohort Study in Singapore (PROMYSE). OCT scans were acquired using Triton DRI-OCT and PLEX Elite 9000. OCT images were segmented both automatically with an established SA-Net architecture and manually using a standard technique with adjudication by two independent graders. SFCT was subsequently determined based on the segmentation. The Bland-Altman plot and intraclass correlation coefficient (ICC) were used to evaluate the agreement., Results: A total of 229 subjects (456 eyes) with mean [± standard deviation (SD)] age of 34.1 (10.4) years were included. The overall SFCT (mean ± SD) based on manual segmentation was 216.9 ± 82.7 µm with Triton DRI-OCT and 239.3 ± 84.3 µm with PLEX Elite 9000. ICC values demonstrated excellent agreement between AI-automated and manual segmented SFCT measurements (PLEX Elite 9000: ICC = 0.937, 95% CI: 0.922 to 0.949, P < 0.001; Triton DRI-OCT: ICC = 0.887, 95% CI: 0.608 to 0.950, P < 0.001). For PLEX Elite 9000, manual segmented measurements were generally thicker when compared to AI-automated segmented measurements, with a fixed bias of 6.3 µm (95% CI: 3.8 to 8.9, P < 0.001) and proportional bias of 0.120 (P < 0.001). On the other hand, manual segmented measurements were comparatively thinner than AI-automated segmented measurements for Triton DRI-OCT, with a fixed bias of - 26.7 µm (95% CI: - 29.7 to - 23.7, P < 0.001) and proportional bias of - 0.090 (P < 0.001)., Conclusion: We observed an excellent agreement in choroidal segmentation measurements when comparing manual with AI-automated techniques, using images from two SS-OCT systems. Given its edge over manual segmentation, automated segmentation may potentially emerge as the primary method of choroidal thickness measurement in the future., (© 2024. The Author(s).)

Microabstract: This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types., Background: This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes., Materials and Methods: A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders., Results: Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, P < .001) and overall survival (HR = 1.853, P = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, P = .028) and overall survival (HR = 1.732, P = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types., Conclusion: Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies., Competing Interests: Disclosure The authors declare no conflicts of interest in relation to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Cancer-related fatigue (CRF) and fear of cancer recurrence (FCR) are two common concerns experienced by cancer survivors. However, the relationship between these two concerns is poorly understood, and whether CRF and FCR influence each other over time is unclear., Methods: Data were from a national, prospective, longitudinal study, the American Cancer Society's Study of Cancer Survivors-I (SCS-I). Surveys were completed by 1395 survivors of 10 different cancer types at three time-points, including assessment 1.3 years (T1), 2.2 years (T2) and 8.8 years (T3) following their cancer diagnosis. CRF was assessed using the fatigue-inertia subscale of the Profile of Mood States, and FCR by the FCR subscale of the Cancer Problems in Living Scale. Multiple group random intercepts cross-lagged panel models investigated prospective associations between CRF and FCR., Results: For younger participants (at or below median age of 55 years, n = 697), CRF at T1 and T2 marginally and significantly predicted FCR at T2 and T3, respectively, but no lagged effects of FCR on subsequent CRF were observed. Cross-lagged effects were not observed for survivors over 55 years of age., Conclusion: Both CRF and FCR are debilitating side effects of cancer and its treatments. Given that CRF may be predictive of FCR, it possible that early detection and intervention for CRF could contribute to lowering FCR severity., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

A new method has been developed for mass spectrometric imaging of small molecules and proteins on tissue or in thinly sliced materials. A laser desorption Venturi electrospray ionization-mass spectrometer was developed for molecular imaging. This method combines laser desorption (LD) and electrospray ionization (ESI) systems before a mass spectrometer (MS). To carry out laser desorption, samples are excited with a laser from the back side of a glass substrate. The desorbed molecules or particles are then captured by a solvent flow. In the ESI system, these desorbed particles and molecules are ionized. The spray part of the solvent system consists of two capillaries: one delivers solvent to the sample plate sides to capture desorbed molecules and particles, and the other carries the solution to the mass spectrometry side using the Venturi effect. A 2D stage facilitates sampling. The system is designed to minimize the sample size after desorption using a 355 nm diode laser, and it is optimized for molecules of various sizes, including organic molecules, amino acids, and proteins. Despite challenging atmospheric conditions for protein desorption, this specialized design enables the collection of protein spectra. The amino acids and other small molecules showed high sensitivity in the MSI measurements. This innovative MS imaging system can be directly applied to real tissue systems and other plant samples to visualize the molecular level distributions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Although partial mesorectal excision (PME) and total mesorectal excision (TME) is primarily indicated for the upper and lower rectal cancer, respectively, few studies have evaluated whether PME or TME is more optimal for middle rectal cancer., Methods: This study included 671 patients with middle and upper rectal cancer who underwent robot-assisted PME or TME. The 2 groups were optimized by propensity score matching of sex, age, clinical stage, tumor location, and neoadjuvant treatment., Results: Complete mesorectal excision was achieved in 617 of 671 patients (92.0%), without showing a difference between the PME and TME groups. Local recurrence rate (5.3% vs. 4.3%, P>0.999) and systemic recurrence rate (8.5% vs. 16.0%, P=0.181) also did not differ between the 2 groups, in patients with middle and upper rectal cancer. The 5-year disease-free survival (81.4% vs. 74.0%, P=0.537) and overall survival (88.0% vs. 81.1%, P=0.847) also did not differ between the PME and TME groups, confined to middle rectal cancer. Moreover, 5-year recurrence and survival rates were not affected by distal resection margins of 2 cm (P=0.112) to 4 cm (P>0.999), regardless of pathological stages. Postoperative complication rate was higher in the TME than in the PME group (21.4% vs. 14.5%, P=0.027). Incontinence was independently associated with TME (odds ratio [OR], 2.009; 95% confidence interval, 1.015-3.975; P=0.045), along with older age (OR, 4.366, P<0.001) and prolonged operation time (OR, 2.196; P=0.500)., Conclusion: PME can be primarily recommended for patients with middle rectal cancer with lower margin of >5 cm from the anal verge.

Background and Objective: In comparison to chemotherapy, enfortumab vedotin (EV) prolonged overall survival in patients with previously treated advanced urothelial carcinoma in EV-301. The objective of the present study was to assess patient experiences of EV versus chemotherapy using patient-reported outcome (PRO) analysis of health-related quality of life (HRQoL)., Methods: For patients in the phase 3 EV-301 trial randomized to EV or chemotherapy we assessed responses to the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) at baseline, weekly for the first 12 wk, and then every 12 wk until discontinuation. We analyzed the QLQ-C30 change from baseline to week 12, the confirmed improvement rate, and the time to improvement or deterioration., Key Findings and Limitations: Baseline PRO compliance rates were 91% for the EV arm (n = 301) and 89% for the chemotherapy arm (n = 307); the corresponding average rates from baseline to week 12 were 70% and 67%. Patients receiving EV versus chemotherapy had reduced pain (difference in change from baseline to week 12: -5.7, 95% confidence interval [CI] -10.8 to -0.7; p = 0.027) and worsening appetite loss (7.3, 95% CI 0.90-13.69; p = 0.026). Larger proportions of patients in the EV arm reported HRQoL improvement from baseline than in the chemotherapy arm; the odds of a confirmed improvement across ten QLQ-C30 function/symptom scales were 1.67 to 2.76 times higher for EV than for chemotherapy. Patients in the EV arm had a shorter time to first confirmed improvement in global health status (GHS)/QoL, fatigue, pain, and physical, role, emotional, and social functioning (all p < 0.05). EV delayed the time to first confirmed deterioration in GHS/QoL (p = 0.027), but worsening appetite loss occurred earlier (p = 0.009) in comparison to chemotherapy., Conclusions and Clinical Implications: HRQoL with EV was maintained, and deterioration in HRQoL was delayed with EV in comparison to chemotherapy. Better results with EV were reported for some scales, with the greatest difference observed for pain. These findings reinforce the EV safety and efficacy outcomes and benefits observed in EV-301., Patient Summary: Patients with previously treated advanced cancer of the urinary tract receiving the drug enfortumab vedotin maintained their HRQoL in comparison to patients treated with chemotherapy. The EV-301 trial is registered on ClinicalTrials.gov as NCT03474107 and on EudraCT as 2017-003344-21., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

We aimed to evaluate the antibacterial activity of phytochemicals with or without an experimental fluoride varnish against Porphyromonas gingivalis. Five phytochemicals, chrysophanol (CHR), emodin (EMO), anthrarufin (ANT), bavachalcone (BCC), and isobavachromene (IBC), were tested using agar diffusion, minimal inhibition concentration (MIC), and minimum bacterial concentration (MBC) assays. We also assessed the cell viability and cytotoxicity of phytochemicals. All phytochemicals showed clear inhibition zones in the agar diffusion test. The inhibition zones of all phytochemical-containing fluoride varnishes were similar to or larger than that of the positive control, excluding that of 1 mM EMO. With or without the fluoride varnish, BCC exhibited the lowest MIC and MBC levels. Cell viability was high in the presence of all phytochemicals except 200 μM EMO. In conclusion, BCC was most effective as a phytochemical alone, while all phytochemical-containing fluoride varnishes inhibited P. gingivalis growth without cytotoxicity.