Adeno-associated virus delivered CXCL9 sensitizes glioblastoma to anti-PD-1 immune checkpoint blockade.

There are numerous mechanisms by which glioblastoma cells evade immunological detection, underscoring the need for strategic combinatorial treatments to achieve appreciable therapeutic effects. However, developing combination therapies is difficult due to dose-limiting toxicities, blood-brain-barrier, and suppressive tumor microenvironment. Glioblastoma is notoriously devoid of lymphocytes driven in part by a paucity of lymphocyte trafficking factors necessary to prompt their recruitment and activation. Herein, we develop a recombinant adeno-associated virus (AAV) gene therapy that enables focal and stable reconstitution of the tumor microenvironment with C-X-C motif ligand 9 (CXCL9), a powerful call-and-receive chemokine for lymphocytes. By manipulating local chemokine directional guidance, AAV-CXCL9 increases tumor infiltration by cytotoxic lymphocytes, sensitizing glioblastoma to anti-PD-1 immune checkpoint blockade in female preclinical tumor models. These effects are accompanied by immunologic signatures evocative of an inflamed tumor microenvironment. These findings support AAV gene therapy as an adjuvant for reconditioning glioblastoma immunogenicity given its safety profile, tropism, modularity, and off-the-shelf capability.

Evaluation of blood and urine based biomarkers for detection of clinically-significant prostate cancer.

BACKGROUND: Recognizing the limitations of prostate-specific antigen (PSA) screening and the morbidity of prostate biopsies, several blood- and urine-based biomarkers have been proposed for pre-biopsy risk stratification. These assays aim to reduce the frequency of unnecessary biopsies (i.e., negative or Grade Group 1 [GG1]) while maintaining highly sensitive detection of clinically significant cancer (GG ≥ 2) prostate cancer. METHODS: We reviewed the literature describing the use of currently available blood- and urine-based biomarkers for detection of GG ≥ 2 cancer, including the Prostate Health Index (PHI), 4Kscore, MyProstateScore (MPS), SelectMDx, ExoDx Prostate Intelliscore (EPI), and IsoPSA. To facilitate clinical application, we focused on the use of biomarkers as a post-PSA secondary test prior to biopsy, as proposed in clinical guidelines. Our outcomes included test performance measures-sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV)-as well as clinical outcomes resulting from biomarker use (i.e., unnecessary biopsies avoided, GG ≥ 2 cancers missed). RESULTS: Contemporary validation data (2015-2023) reveal that currently available biomarkers provide ~15-50% specificity at a sensitivity of 90-95% for GG ≥ 2 PCa. Clinically, this indicates that secondary use of biomarker testing in men with elevated PSA could allow for avoidance of up to 15-50% of unnecessary prostate biopsies, while preserving detection of 90-95% of GG ≥ 2 cancers that would be detected under the traditional "biopsy all" approach. CONCLUSIONS: The contemporary literature further supports the proposed role of post-PSA biomarker testing to reduce the use of invasive biopsy while maintaining highly sensitive detection of GG ≥ 2 cancer. Questions remain regarding the optimal application of biomarkers in combination or in sequence with mpMRI.

Third-Generation Anticancer Photodynamic Therapy Systems Based on Star-like Anionic Polyacrylamide Polymer, Gold Nanoparticles, and Temoporfin Photosensitizer.

Photodynamic therapy (PDT) is a non-invasive anticancer treatment that uses special photosensitizer molecules (PS) to generate singlet oxygen and other reactive oxygen species (ROS) in a tissue under excitation with red or infrared light. Though the method has been known for decades, it has become more popular recently with the development of new efficient organic dyes and LED light sources. Here we introduce a ternary nanocomposite: water-soluble star-like polymer/gold nanoparticles (AuNP)/temoporfin PS, which can be considered as a third-generation PDT system. AuNPs were synthesized in situ inside the polymer molecules, and the latter were then loaded with PS molecules in an aqueous solution. The applied method of synthesis allows precise control of the size and architecture of polymer nanoparticles as well as the concentration of the components. Dynamic light scattering confirmed the formation of isolated particles (120 nm diameter) with AuNPs and PS molecules incorporated inside the polymer shell. Absorption and photoluminescence spectroscopies revealed optimal concentrations of the components that can simultaneously reduce the side effects of dark toxicity and enhance singlet oxygen generation to increase cancer cell mortality. Here, we report on the optical properties of the system and detailed mechanisms of the observed enhancement of the phototherapeutic effect. Combinations of organic dyes with gold nanoparticles allow significant enhancement of the effect of ROS generation due to surface plasmonic resonance in the latter, while the application of a biocompatible star-like polymer vehicle with a dextran core and anionic polyacrylamide arms allows better local integration of the components and targeted delivery of the PS molecules to cancer cells. In this study, we demonstrate, as proof of concept, a successful application of the developed PDT system for in vitro treatment of triple-negative breast cancer cells under irradiation with a low-power LED lamp (660 nm). We consider the developed nanocomposite to be a promising PDT system for application to other types of cancer.

Corals survive severe bleaching event in refuges related to taxa, colony size, and water depth.

Marine heatwaves are increasing in frequency and duration, threatening tropical reef ecosystems through intensified coral bleaching events. We examined a strikingly variable spatial pattern of bleaching in Moorea, French Polynesia following a heatwave that lasted from November 2018 to July 2019. In July 2019, four months after the onset of bleaching, we surveyed > 5000 individual colonies of the two dominant coral genera, Pocillopora and Acropora, at 10 m and 17 m water depths, at six forereef sites around the island where temperature was measured. We found severe bleaching increased with colony size for both coral genera, but Acropora bleached more severely than Pocillopora overall. Acropora bleached more at 10 m than 17 m, likely due to higher light availability at 10 m compared to 17 m, or greater daily temperature fluctuation at depth. Bleaching in Pocillopora corals did not differ with depth but instead varied with the interaction of colony size and Accumulated Heat Stress (AHS), in that larger colonies (> 30 cm) were more sensitive to AHS than mid-size (10-29 cm) or small colonies (5-9 cm). Our findings provide insight into complex interactions among coral taxa, colony size, and water depth that produce high spatial variation in bleaching and related coral mortality.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer.

Importance: Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). Objective: To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. Design, Setting, and Participants: RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Exposure: Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Main Outcomes and Measures: Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Results: Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. Conclusions and Relevance: In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.

Musculoskeletal injuries during trail sports: Sex- and age-specific analyses over 20 years from a national injury database.

INTRODUCTION: Musculoskeletal (MSK) injuries in US trail sports are understudied as trail sport popularity grows. This study describes MSK injury patterns among hikers, trail runners, and mountain bikers from 2002 through 2021 and investigates MSK injury trends acquired during mountain sports. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify US emergency department (ED) patients from 2002-2021 (inclusive) who endured MSK injuries during hiking, trail running, or mountain biking. Injury rates and national estimates were calculated across demographics. RESULTS: 9835 injuries were included (48.4% male, 51.6% female). Injuries increased over time, with 1213 from 2002-2005 versus 2417 from 2018-2021. No sex differences existed before 2010, after which female injury rates exceeded those of males. The following findings were statistically significant, with P<0.05: females endured more fractures and strains/sprains; males endured more lacerations; concussions and head injuries were higher among those <18 y; dislocations and strains/sprains were higher for 18 to 65 y; fractures were higher for >65 y; <18 y had high mountain-biking and low running rates; 18 to 65 y had high running rates; and >65 y had low biking and running rates. Although all diagnoses increased in number over time, no significant differences existed in the proportion of any given diagnosis relative to total injuries. CONCLUSIONS: MSK injuries during trail sports have increased since 2002. Males endured more injuries until 2009, after which females endured more. Significant sex and age differences were found regarding injury diagnosis and body parts. Further studies are needed to confirm these trends and their causes.

Effect of Antibiotic Spacer Dosing on Treatment Success in Two-Stage Exchange for Periprosthetic Joint Infection.

INTRODUCTION: In two-stage exchange for periprosthetic joint infection (PJI), adding antibiotics to cement spacers is the standard of care; however, little is known about optimal dosage. There is emphasis on using >3.6 g of total antibiotic, including ≥2.0 g of vancomycin, per 40 g of cement, but these recommendations lack clinical evidence. We examined whether recommended antibiotic spacer doses affect treatment success. METHODS: This was a retrospective review of 202 patients who underwent two-stage exchange for PJI from 2004 to 2020 with at least 1-year follow-up. Patients were separated into high (>3.6 g of total antibiotic per 40 g of cement) and low-dose spacer groups. Primary outcomes were overall and infectious failure. RESULTS: High-dose spacers were used in 80% (162/202) of patients. High-dose spacers had a reduced risk of overall (OR, 0.37; P = 0.024) and infectious (OR, 0.35; P = 0.020) failure for infected primary arthroplasties, but not revisions. In multivariate analysis, vancomycin dose ≥2.0 g decreased the risk of infectious failure (OR, 0.31; P = 0.016), although not overall failure (OR, 0.51; P = 0.147). CONCLUSION: During two-stage exchange for PJI, spacers with greater than 3.6 g of total antibiotic may reduce overall and infectious failure for infected primary arthroplasties. Furthermore, using at least 2.0 g of vancomycin could independently decrease the risk of infectious failure.

Sjögren's disease activity associates with cardiovascular disease and monoclonal gammopathy: a university cohort study of disease activity and comorbidities.

BACKGROUND: We used the University of Wisconsin cohort to determine the extent to which the EULAR Sjögren's syndrome disease activity index (ESSDAI) was associated with comorbidities that contribute to mortality. METHODS: Our University of Wisconsin, Madison cohort had 111 patients with Sjögren's Disease (SjD) by 2016 ACR/EULAR criteria and 194 control patients with sicca. Our study was performed from March 1st, 2020 through April 1st, 2023. We collected data using a standardized collection tool, including components of the Charlson Comorbidity Index (CCI). Stratifying our SjD patients by ESSDAI < 5 and ESSDAI ≥ 5, we assessed differences in comorbidities associated with mortality. RESULTS: At time of SjD diagnosis, the ESSDAI ≥ 5 group had increased odds of peripheral vascular disease compared to controls (OR 10.17; 95% CI 1.18-87.87). Patients with a current ESSDAI ≥ 5 were more likely to have a myocardial infarction compared to controls (OR 9.87; 95% CI 1.17-83.49). SjD patients had increased prevalence of monoclonal gammopathy compared to controls (9.3% vs 0.5%, p < 0.001). SjD patients with high ESSDAI at diagnosis had greater prevalence of monoclonal gammopathy compared to the SjD patients with a low ESSDAI (16% vs 5%, p = .04). As reported elsewhere, the ESSDAI ≥ 5 group had increased odds of chronic pulmonary disease (OR 4.37; 95% CI 1.59-11.97). CONCLUSION: We found high ESSDAI scores were associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. Furthermore, monoclonal gammopathy was more frequent in SjD patients compared to sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario. Key Points • High ESSDAI scores are associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. • Monoclonal gammopathy is more frequent in SjD patients than sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario.

Increasing radial growth in old-growth high-elevation conifers in Southern California, USA, during the exceptional "hot drought" of 2000-2020.

Hot droughts, droughts attributed to below-average precipitation and exceptional warmth, are increasingly common in the twenty-first century, yet little is known about their effect on coniferous tree growth because of their historical rarity. In much of the American West, including California, radial tree growth is principally driven by precipitation, and narrow ring widths are typically associated with either drier or drought conditions. However, for species growing at high elevations (e.g., Larix lyalli, Pinus albicaulis), growth can be closely aligned with above-average temperatures with maximum growth coinciding with meteorological drought, suggesting that the growth effects of drought span from adverse to beneficial depending on location. Here, we compare radial growth responses of three high-elevation old-growth pines (Pinus jeffreyi, P. lambertiana, and P. contorta) growing in the San Jacinto Mountains, California, during a twenty-first-century hot drought (2000-2020) largely caused by exceptional warmth and a twentieth-century drought (1959-1966) principally driven by precipitation deficits. Mean radial growth during the hot drought was 12% above average while 18% below average during the mid-century drought illustrating that the consequences of environmental stress exhibit spatiotemporal variability. We conclude that the effects of hot droughts on tree growth in high-elevation forests may produce responses different than what is commonly associated with extended dry periods for much of western North America's forested lands at lower elevational ranges and likely applies to other mountainous regions (e.g., Mediterranean Europe) defined by summer-dry conditions. Thus, the climatological/biological interactions discovered in Southern California may offer clues to the unique nature of high-elevation forested ecosystems globally.

Regional differences in fishing behavior determine whether a marine reserve network enhances fishery yield.

A network of marine reserves can enhance yield in depleted fisheries by protecting populations, particularly large, old spawners that supply larvae for interspersed fishing grounds. The ability of marine reserves to enhance sustainable fisheries is much less evident. We report empirical evidence of a marine reserve network improving yield regionally for a sustainable spiny lobster fishery, apparently through the spillover of adult lobsters and behavioral adaptation by the fishing fleet. Results of a Before-After, Control-Impact analysis found catch, effort, and Catch-Per-Unit Effort increased after the establishment of marine reserves in the northern region of the fishery where fishers responded by fishing intensively at reserve borders, but declined in the southern region where they vacated once productive fishing grounds. The adaptation of the northern region of the fishery may have been aided by a history of collaboration between fishers, scientists, and managers, highlighting the value of collaborative research and education programs for preparing fisheries to operate productively within a seascape that includes a large marine reserve network.

Applicant Perceptions of Postinterview Communication During the 2022 to 2023 Neurosurgery Recruitment Cycle: A Cross-Sectional Survey Study.

OBJECTIVES: To evaluate and describe neurosurgery applicant perceptions of the postinterview communication (PIC) process during the US residency match. METHODS: A voluntary and anonymous postmatch web-based survey was developed and sent to 209 candidates who applied to 1 academic neurosurgery practice during the 2022-2023 recruitment cycle, approximately 1 week following match day. Survey questions focused on their perceptions of and participation behaviors with PIC and how this impacted their final rank list. RESULTS: Seventy-eight (37.3%) of the 209 candidates responded to the survey. Sixty-four (84.2%) respondents reported submitting a letter of intent (LOI) to their number 1 ranked program. Sixty-one (82%) felt pressured to send a LOI to improve their rank status, fearing that it may harm them if they did not. Fifty-four (73.0%) respondents felt pressured to send an early LOI despite not seeing the program in person to communicate interest before programs certified their rank lists. Fourteen (18.9%) respondents agreed that a second look experience impacted their rank list enough to where they regretted an early LOI. Fifty-five (76.4%) respondents disagreed that second-look attendance had no impact on their rank status with a program. Fifty (71.4%) respondents agreed that PIC causes undue stress during the match process. Sixty-one (84.7%) respondents agreed that aspects of PIC require universal guidelines. CONCLUSIONS: This is the first study to describe the perceptions of PIC and behaviors of neurosurgery applicants during the US residency match process. Standardized PIC practices may help to ensure transparency and relieve stress for applicants during the match process.

Health impacts of poor water quality on an endangered shorebird breeding programme in Aotearoa New Zealand.

CASE HISTORY: Two clusters of mortality among endangered tuturuatu/tchuriwat'/shore plover (Thinornis novaeseelandiae) have occurred at captive breeding facilities around New Zealand in recent years. In the first, four chicks died at Pukaha National Wildlife Centre (Mount Bruce, NZ) in February 2016, and in the second five adult birds at the Cape Sanctuary (Cape Kidnappers, NZ) died in 2022. CLINICAL FINDINGS: In 2016, four chicks were noted to become weak, have increased vocalisations and closed eyes prior to death. The remaining chicks were treated for 5 days with amoxycillin/clavulanate orally twice daily. Water containers and brooders were cleaned and disinfected with chlorhexidine. No further mortality was seen.In the 2022 cluster, three adult breeding birds died acutely and five others showed inappetence, weight loss and diarrhoea approximately 10 days after heavy rains flooded the local river. The five birds were treated with amoxycillin/clavulanate orally twice daily and oral fluids for 5 days. Two birds died and three survived. No breeding occurred in the aviaries in the following season. PATHOLOGICAL FINDINGS: In 2016, the chicks showed pulmonary changes ranging from congestion and oedema to heterophilic inflammation consistent with septicaemia.In 2022, the adult birds showed proliferation of bacteria in the distal small intestine associated with mucosal ulceration and heterophilic infiltration. Acid-fast staining of the caecal contents in one bird showed organisms consistent with Cryptosporidium spp. LABORATORY FINDINGS: Aerobic bacterial cultures of the lung and liver of two affected chicks carried out in 2016 showed heavy growth of Plesiomonas shigelloides. The same organism was cultured from water trays and holding tanks containing water boatmen (Sigara arguta) on which the chicks were fed.In 2022, cultures from the livers of three dead birds each showed a mixed bacterial growth with differing dominant organisms (Aeromonas sobria, Hafnia alvei, Citrobacter freundii and an Enterococcus sp.). PCR and sequencing confirmed Cryptosporidium parvum in the caecum of one bird. Fresh faeces from 24 breeding birds from the captive breeding facilities were negative by PCR for Cryptosporidium spp.The captive breeding facilities obtain water for the aviaries and aquatic invertebrates to feed to the chicks from local freshwater sources. Water quality testing at the Cape Sanctuary revealed concentrations of faecal indicator bacteria in excess of safe drinking water guidelines, with peaks following heavy rainfall. CLINICAL RELEVANCE: Fluctuations in water quality associated with mammalian faecal bacteria can adversely affect bird health and impact on captive rearing of endangered wildlife.

A Ketone Monoester with Carbohydrate Improves Cognitive Measures Postexercise, but Not Performance in Trained Females.

PURPOSE: The acute ingestion of a ketone monoester with the coingestion of a carbohydrate (KME + CHO) compared with carbohydrate (CHO) was investigated on cycling performance and cognitive performance in trained females. METHODS: Using a two condition, placebo-controlled, double-blinded and crossover design, 12 trained females (mean ± SD: age, 23 ± 3 yr; height, 1.64 ± 0.08 m; mass, 65.2 ± 12.7 kg) completed a baseline assessment of cognitive performance (psychomotor vigilance testing (PVT), task switching, and incongruent flanker), followed by 6 × 5-min intervals at 40%, 45%, 50%, 55%, 60%, and 65% of their maximal power output (W max ) and then a 10-km time trial, concluding with the same assessments of cognitive performance. Participants consumed either 375 mg·kg -1 body mass of KME with a 6% CHO solution (1 g·min -1 of exercise) or CHO alone, across three boluses (50:25:25). RESULTS: Blood ß-hydroxybutyrate concentrations averaged 1.80 ± 0.07 and 0.13 ± 0.01 mM during exercise in KME + CHO and CHO, respectively. Blood glucose decreased after drink 1 of KME + CHO (~15%; P = 0.01) but not CHO, and lactate concentrations were lower in KME + CHO at 50%, 55%, 60%, and 65% W max (all P < 0.05) compared with CHO. Despite these changes, no differences were found between conditions for time trial finishing times (KME + CHO, 29.7 ± 5.7 min; CHO, 29.6 ± 5.7 min; P = 0.92). However, only KME + CHO resulted in increases in psychomotor vigilance testing speed (~4%; P = 0.01) and faster reaction times (~14%; P < 0.01), speed (~15%; P < 0.01), and correct responses (~13%; P = 0.03) in the incongruent flanker during posttesting compared with CHO. CONCLUSIONS: The acute ingestion of a KME + CHO elevated blood ß-hydroxybutyrate and lowered glucose and lactate across multiple time points during exercise compared with CHO. Although these changes did not affect physical performance, several markers of cognitive performance were improved by the addition of a KME in trained females.

Extensive cellular multi-tasking within Bacillus subtilis biofilms.

Bacillus subtilis is a soil-dwelling bacterium that can form biofilms, or communities of cells surrounded by a self-produced extracellular matrix. In biofilms, genetically identical cells often exhibit heterogeneous transcriptional phenotypes, so that subpopulations of cells carry out essential yet costly cellular processes that allow the entire population to thrive. Surprisingly, the extent of phenotypic heterogeneity and the relationships between subpopulations of cells within biofilms of even in well-studied bacterial systems like B. subtilis remains largely unknown. To determine relationships between these subpopulations of cells, we created 182 strains containing pairwise combinations of fluorescent transcriptional reporters for the expression state of 14 different genes associated with potential cellular subpopulations. We determined the spatial organization of the expression of these genes within biofilms using confocal microscopy, which revealed that many reporters localized to distinct areas of the biofilm, some of which were co-localized. We used flow cytometry to quantify reporter co-expression, which revealed that many cells "multi-task," simultaneously expressing two reporters. These data indicate that prior models describing B. subtilis cells as differentiating into specific cell types, each with a specific task or function, were oversimplified. Only a few subpopulations of cells, including surfactin and plipastatin producers, as well as sporulating and competent cells, appear to have distinct roles based on the set of genes examined here. These data will provide us with a framework with which to further study and make predictions about the roles of diverse cellular phenotypes in B. subtilis biofilms. IMPORTANCE Many microbes differentiate, expressing diverse phenotypes to ensure their survival in various environments. However, studies on phenotypic differentiation have typically examined only a few phenotypes at one time, thus limiting our knowledge about the extent of differentiation and phenotypic overlap in the population. We investigated the spatial organization and gene expression relationships for genes important in B. subtilis biofilms. In doing so, we mapped spatial gene expression patterns and expanded the number of cell populations described in the B. subtilis literature. It is likely that other bacteria also display complex differentiation patterns within their biofilms. Studying the extent of cellular differentiation in other microbes may be important when designing therapies for disease-causing bacteria, where studying only a single phenotype may be masking underlying phenotypic differentiation relevant to infection outcomes.

Childhood cancer incidence & survival in Aotearoa, New Zealand 2010-2019.

OBJECTIVE: To provide updated estimates of childhood cancer incidence and survival in Aotearoa, New Zealand. METHOD: Registrations for children under the age of 15 years diagnosed with cancer between 2010 and 2019 were extracted from the New Zealand Children's Cancer Registry. Cases were stratified by age, sex, prioritised ethnicity (Maori, Pacific peoples, and non-Maori) and cancer type. Age-standardised incidence rates (ASRs) per million person years and observed survival rates were calculated. RESULTS: During the study period, 1522 children were diagnosed with cancer providing an ASR of 169.1 per million per year (95 % Confidence Interval, CI: 157.0-181.2). For all childhood cancers combined, survival at 5-years was 85.6 % (95 % CI 83.7-87.3). There was a gap in 5-year survival between Maori (80.9 %, 95 % CI 76.5-84.6), Pacific peoples (82.6 %, 95 % CI 75.6-87,7) and Non-Maori (87.8 %, 95 % CI 85.6-89.7) In both adjusted and unadjusted models, this difference in survival was most marked (p < 0.05) among children who were 10-14 years of age at diagnosis. CONCLUSION: Childhood cancer incidence and survival rates in Aotearoa, New Zealand remain comparable to other high-income countries. Further research is required to understand the survival difference between ethnic groups.

Association of Injury Rates Among Players in the National Football League With Playoff Qualification, Travel Distance, Game Timing, and the Addition of Another Game: Data From the 2017 to 2022 Seasons.

Background: Injury incidence is higher in the National Football League (NFL) than in other collision sports. Although previous research has identified that scheduling variations, including overseas games and bye week timing, does not affect concussion risk, data are currently lacking regarding the effects of scheduling variation on season-long musculoskeletal injury incidence. Purpose: To determine whether higher cumulative travel distance, overseas play, an early season bye week, and an expansion of the regular season is associated with higher injury rates in the NFL. Study Design: Descriptive epidemiology study. Methods: All 1275 injuries across 5 NFL seasons from 2017 to 2018 through 2021 to 2022 were reviewed retrospectively. Injury data and travel distances were extracted from publicly available sources, which were cross-referenced for validation. Injury rates were calculated per 1000 athletic-exposures (AEs). Cumulative team travel distances were compared statistically using a linear regression. Single factor analysis of variance was used to compare categorical variables. Results: Travel distance did not significantly predict injury rates (P = .47), and there was no difference in injury rates between teams that played a game overseas versus teams that did not (19.3 injuries per 1000 AEs for both; P = .96). In addition, no difference was found in injury rates (F[109,2100[ = 0.704; P = .73) or players placed on the injured reserve list (F[99,778] = 1.70; P = .077) between various bye weeks (P = .73). Injury rates did not differ between the new 17-game regular season (18.4 per 1000 AEs) versus the previous four 16-game regular seasons (19.7 per 1000 AEs; P = .12). However, teams that did not qualify for the playoffs had a significantly higher injury rate (19.9 per 1000 AEs) as well as players on injured reserve (8.0 per 1000 AEs) than playoff-qualifying teams (18.4 and 6.8 per 1000 AEs, respectively; P < .05 for both). Conclusion: Over 5 NFL seasons, cumulative travel distance, overseas play, bye week timing, and adding 1 regular season game were not associated with increased injury rates in NFL players. However, a lack of regular season success was associated with higher injury rates and more players on injured reserve.

Sex-Based Differences in Prevalence, Outcomes, and Complications of Hip Arthroscopy for Femoroacetabular Impingement: A Systematic Review and Meta-analysis.

Background: Trends between the sexes have been reported regarding prevalence, patient-reported outcomes (PROs), and complications of hip arthroscopy (HA) for femoroacetabular impingement syndrome (FAIS), yet current results lack consensus. Purpose: To evaluate sex-based differences after HA for FAIS in (1) prevalence of cam and pincer morphology in FAIS and (2) PROs, pain scores, and postoperative complication rates. Study Design: Systematic review; Level of evidence, 4. Methods: The EMBASE, PubMed, and Ovid (MEDLINE) databases were searched from establishment to February 28, 2022, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Included studies had sex-based data on prevalence, outcomes, and complications of HA for FAIS. Reviews and commentaries were excluded. Data were combined, and between-sex differences were analyzed. Meta-analyses using random-effects models were performed when possible. Pooled risk ratios (RRs) and standardized mean differences were calculated. Results: A total of 74 studies were included (213,059 patients; 132,973 female hips [62.4%] and 80,086 male hips [37.6%]). The mean age was 30.7 ± 7.7 years among male patients and 31.1 ± 7.8 years among female patients. Male patients experienced mixed-type impingement significantly more often (39.4% vs 27.2% for female patients; RR = 0.69 [95% confidence interval [CI], 0.58-0.81]; P < .001), whereas female patients experienced pincer-type impingement more often (50.6% vs 30.8% for male patients; RR = 2.35 [95% CI, 1.14-4.86]; P = .02). Male patients had higher likelihoods of undergoing femoroplasty (89.8% vs 77.4% for female patients; RR = 0.90 [95% CI, 0.83-0.97]; P = .006), acetabuloplasty (67.1% vs 59.3% for female patients; RR = 0.87 [95% CI, 0.79-0.97]; P = .01), or combined femoroplasty/acetabuloplasty (29.2% vs 14.5% for female patients; RR = 0.63 [95% CI, 0.44-0.90]; P = .01). Although female patients showed greater improvements in Hip Outcome Score-Sport-Specific subscale (P = .005), modified Harris Hip Score (P = .006), and visual analog scale pain (P < .001), both sexes surpassed the minimal clinically important difference at 1, 2, and 5 years postoperatively. Female patients had higher complication rates (P = .003), although no sex-based differences were found in total hip arthroplasty conversion rates (P = .21). Conclusion: Male patients undergoing HA for FAIS had a higher prevalence of mixed-type FAIS while female patients had more pincer-type FAIS. Female patients gained greater improvements in PROs, although both sexes exceeded the minimal clinically important difference, suggesting that both male and female patients can benefit from HA.