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There is limited research examining the association between wildfire smoke, an increasingly frequent exposure, and headache-related emergency department (ED) visits, despite headaches being a leading cause of years lived with disability globally. To examine the association between wildfire-sourced fine particulate matter with an aerodynamic diameter of 2.5 μm or less (PM2.5) and ED visit for migraine and other primary headache syndromes (MOPHS) compared with nonwildfire-sourced PM2.5, and to assess the variation across sociodemographic factors. This case-crossover study used conditional logistic regression to examine ED visits during wildfire seasons (May 1 to October 31) from 2010 to 2023 in Alberta and Ontario provinces in Canada. Case days were matched to referent days by day of week, month, year, and forward sortation area (first 3 postal code characters). Seven-day cumulative lags were evaluated. All ED visits recorded in the National Ambulatory Care Reporting System with a primary diagnosis of MOPHS were included. Statistical analyses were conducted from April to December 2025. Total PM2.5 concentrations and wildfire day (WFD). Daily mean wildfire-sourced PM2.5 was estimated using the Canadian Optimized Statistical Smoke Exposure Model. WFDs were defined by smoke plume presence and total PM2.5 concentration exceeding a predefined threshold based on the mean plus 1.5 SD of PM2.5 on days without a smoke plume. Wildfire-sourced PM2.5 was defined as the difference between total PM2.5 concentration on a WFD and expected background PM2.5 concentration on non-WFDs. ED visits for migraine (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Canada code G43) and other primary headache syndromes (code G44). Among the 997 701 ED visits for 622 753 patients (mean [SD] age, 24.6 [16.8] years; 760 795 females [76.3%]) for MOPHS identified during the study period, 86.2% of visits were for migraines and 13.8% were for other primary headache syndromes. Wildfire-sourced PM2.5 was associated with a 6.07% (95% CI, 5.75%-6.39%) increase in ED visits. Associations appeared attenuated in the least materially and socially deprived quantile (for both provinces combined, the percentage increase in MOPHS was smallest for the Material and Social Deprivation Index quintile 1: 3.61% [95% CI, 1.93%-5.63%] and largest for quintile 5: 10.42% [95% CI, 7.41%-13.49%]). In contrast, total PM2.5 concentration on non-WFDs was not significantly associated with ED visits (0.21%; 95% CI, -0.20% to 0.62%). In this case-crossover study of ED visits in Alberta and Ontario, acute exposure to wildfire-sourced PM2.5 was associated with increased ED visit for MOPHS; associations were greater in magnitude for wildfire-sourced PM2.5 than nonwildfire-sourced PM2.5. These findings support the need for further research into wildfire smoke and severe headache-related outcomes.

Knee osteoarthritis is a common and debilitating problem. Safe and effective nonoperative treatments with sustained outcomes are needed, especially for patients unsuitable for knee replacement. Cooled radiofrequency ablation (CRFA) and hyaluronic acid (HA) injection have demonstrated efficacy, but CRFA is less well studied in Asian populations. In this prospective, open-label, randomised controlled pilot study, patients with chronic knee osteoarthritis seen at a single tertiary centre in Singapore, who had at least 50% pain reduction after a genicular nerve block, were allocated to undergo CRFA or receive a single 6 mL injection of HA. Visual Analogue Scale (VAS) for pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee scores, Knee Injury and Osteoarthritis Outcome Score (KOOS), EuroQol-5 Dimensions-5 Level and Global Perceived Effect were compared at 2 weeks, 1 month, 3 months and 6 months after treatment. Twelve participants underwent intervention (7 CRFA and 5 HA), and 11 completed follow-up to 6 months (7 CRFA and 4 HA). Responder rates at 6 months were 40.0% (95% confidence interval [CI] 11.8%-76.9%) for HA and 28.6% (95% CI 8.2%-64.1%) for CRFA. Over time, VAS, KOOS and WOMAC pain scores and GPE improved in both groups, with peak improvement at 1 month. Adverse events were generally minor and self-limiting. Intergroup differences were not statistically significant. Both interventions were safe and efficacious for knee osteoarthritis. Owing to the small sample size, the findings were preliminary and hypothesis-generating. Larger studies comparing CRFA with other interventions for knee osteoarthritis in the Singapore population are warranted.

Background: Developmental dysplasia of the hip (DDH) is one of the leading causes of secondary hip osteoarthritis and frequently results in severe anatomical alterations that make total hip arthroplasty (THA) technically demanding. Restoration of hip biomechanics, limb length, and joint stability remains challenging, particularly in patients with moderate-to-severe dysplasia. Objective: To evaluate the clinical and radiographic outcomes of cementless total hip arthroplasty combined with soft-tissue balancing, with or without acetabular reconstruction using autologous femoral head graft, in patients affected by osteoarthritis secondary to DDH. Methods: A retrospective single-center case series was conducted on eight female patients (mean age 53.9 &#xb1; 14.6 years; range 33-80 years) who underwent primary cementless THA for DDH-related osteoarthritis between 2019 and 2025. Clinical outcomes were assessed using the Harris Hip Score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Short Form-36 (SF-36). Radiographic evaluation included implant positioning, osteolysis, heterotopic ossification, bone graft incorporation, and leg-length discrepancy. Data normality was assessed using the Shapiro-Wilk test. Preoperative and postoperative outcomes were compared using paired Student's t-test and confirmed with the Wilcoxon signed-rank test. Implant survival and revision-free status were recorded throughout the follow-up period. Results: At a minimum follow-up of 12 months (range 12 months-6 years), significant improvements were observed in all clinical outcome measures. Mean HHS increased from 49.3 &#xb1; 2.5 preoperatively to 90.4 &#xb1; 2.7 postoperatively (p < 0.001), while mean WOMAC decreased from 53.5 &#xb1; 5.6 to 7.4 &#xb1; 3.3 (p < 0.001). Mean SF-36 improved from 47.2 &#xb1; 3.8 to 89.9 &#xb1; 3.2 (p < 0.001). Wilcoxon analysis confirmed the statistical significance of these findings (all p = 0.0078). Radiographic assessment demonstrated satisfactory implant positioning and stable fixation in all patients, with no evidence of osteolysis or implant loosening. Minor complications included one intraoperative periprosthetic femoral fracture treated successfully with cerclage wiring, two cases of Brooker grade I-II heterotopic ossification, and one case of minimal graft resorption without clinical consequences. No revision procedures were recorded during follow-up, and implant survival was 100%. Conclusions: Cementless THA combined with selective soft-tissue balancing provides excellent clinical, functional, and radiographic outcomes in patients with osteoarthritis secondary to DDH. This approach significantly improves hip function and quality of life while ensuring stable implant fixation, low complication rates, and excellent mid-term implant survival.

Indigenous people using substances experience health disparities that are compounded by systemic inequities shaped by colonialism. The WHiSE 2.0 study aims to describe substance use patterns and harm reduction approaches among Indigenous people who use drugs in Thunder Bay, Sudbury, and Sault Ste Marie. A community-based research approach was used and guided by Indigenous leadership. Eligible study participants self-identified as Indigenous, lived in the study regions, and used substances within the last 3 months. Participants completed an interviewer-administered 1-hour questionnaire. Descriptive statistics were conducted to summarize participant demographic and cultural characteristics, impacts of colonization, substance use and health behaviours, and harm reduction knowledge, stratified by city. A total of 356 participants were enrolled: 173 in Thunder Bay, 101 in Sault Ste. Marie, and 82 in Sudbury. Most identified as First Nations with 93.1% in Thunder Bay, 76.8% in Sudbury, and 75.2% in Sault Ste. Marie. The percentage of participants across all sites with precarious sleeping situations was high, with 39.0% sleeping on the street, 28.3% staying in a shelter, and 23.3% couch surfing as well as 41.9% staying at a family or friend's home. Across all sites, 43.3% of participants injected drugs, 31.5% ingested drugs, 92.1% smoked drugs, and 38.5% snorted or inhaled drugs. Importantly across all sites, 84.0% knew what harm reduction was, and 82.3% of respondents had ever had HIV screening test and 84.3% hepatitis C testing. Also, 71.3% of all participants engaged in ceremonies and 22.2% reported that cultural teachings affected their harm reduction practices. WHiSE 2.0 is the first prospective cohort study examining the harm reduction needs of Indigenous people using substances in northern Ontario. Through a culturally grounded, community-led study, urgent service gaps are highlighted and the importance of locally tailored harm reduction strategies rooted in Indigenous knowledge and leadership.

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Advanced hemodynamic monitoring may provide clinical information during early post-resuscitation care after out-of-hospital cardiac arrest (OHCA), but practices, treatment targets, and responses to abnormal values remain incompletely defined. We aimed to map the available evidence on advanced hemodynamic monitoring after OHCA. We conducted a scoping review in accordance with a prespecified protocol and the PRISMA-ScR methodology. Eligible studies included hospitalized adults after OHCA and reported advanced hemodynamic variables beyond routine arterial blood pressure monitoring. We extracted data on study design, population, monitoring modality, variables assessed, hemodynamic targets or thresholds, treatment approaches, and reported associations with clinical outcomes. Twenty-eight studies were included. The most frequently reported hemodynamic variables were cardiac output (27/28 studies), mean arterial pressure (MAP, 25/28), central venous pressure (17/28), and mixed venous oxygen saturation (SvO2, 14/28), whereas pulmonary vascular variables and pulmonary capillary wedge pressure were less commonly studied. Monitoring was predominantly invasive and most often based on pulmonary artery catheterization. Prognostic associations were heterogeneous: cardiac output showed inconsistent associations with outcomes, whereas low SvO2 and elevated pulmonary artery pressure were associated with worse outcomes in some studies. Hemodynamic targets were variably defined and were most frequently related to MAP-targets. Advanced hemodynamic monitoring after OHCA remains heterogeneous, with a focus mainly on MAP and cardiac output. No single variable was consistently associated with prognosis or treatment response, although low SvO2 and elevated pulmonary artery pressure were associated with worse outcomes. Future studies should evaluate strategies integrating multiple hemodynamic variables and individualized patient-centred hemodynamic targets.

Patient safety and systems integration (PSSI) simulations help uncover hazards that jeopardise patient safety. Using direct observation, video analysis and systems-focused debriefing, they identify and categorise latent safety threats (LSTs). We aimed to compare the number, nature and potential risk of LSTs across the three modalities. In a prospective observational cohort, six unannounced simulations were conducted in a paediatric emergency department during active shifts. Two raters independently identified LSTs, which were coded deductively using the adapted Systems Engineering Initiative for Patient Safety (SEIPS) framework and inductively for emergent themes. Harm potential was graded using Healthcare Failure Mode and Effect Analysis (HFMEA). LSTs were mapped onto a framework matrix for comparison within and across detection modalities. The primary outcome was differences in LSTs detected by each modality; number, nature (SEIPS) and proportion of critical threats (HFMEA score &#x2265;8). Seventy-two providers participated (mean 12.0&#xb1;2.3/simulation). 2576 unique LSTs were identified. Video detected the most LSTs (n=1908), compared with observation (n=426) or debriefing (n=242, p<0.01). Although fewer overall, debriefing yielded the highest proportion of critical threats (54.9% (124/226), p<0.01) compared with observation (26.3% (109/414)) or video (23.6% (442/1875)). Debriefing often revealed task-specific and communication-related threats, whereas video excelled at physical workspace and infection control deficits. Inter-rater reliability for SEIPS coding was acceptable (&#x3ba;&#x2265;0.7). Although debriefing yielded fewer LSTs, it is valuable for surfacing critical LSTs (54.9% vs 23.6% video). We highlight the strengths of LST detection modalities and provide insights for institutions selecting strategies to mitigate harm and enhance system resilience.

Accurate early prognostication in patients with acute brain injury remains a major challenge in neurocritical care. Conventional bedside assessments provide limited insight into long-term outcomes and may not fully capture preserved brain function that supports recovery. Functional neuroimaging can detect brain activity not evident at the bedside, but its use in intensive care remains constrained by cost, logistics, and the need for stronger evidence supporting its value. Functional near-infrared spectroscopy (fNIRS) offers a scalable, bedside-compatible approach for assessing brain function in critically ill patients, but its value for early prognostication has yet to be established. In this prospective observational cohort study, 33 patients with acute brain injury in the intensive care unit (ICU) underwent fNIRS recording while listening to two audio-only movie clips. Functional connectivity features were used to train a machine learning model to classify 6-month functional outcome, defined by the Glasgow Outcome Scale-Extended (favorable&#x2009;&#x2265;&#x2009;4, unfavorable&#x2009;<&#x2009;4). Model performance was assessed using balanced accuracy and statistically evaluated using permutation testing. Performance was compared with validated behavioral assessments and clinical variables. Secondary analyses evaluated prediction of behavioral responsiveness (observable command-following after testing) and covert awareness (neural command-following). A total of 26 patients had an unfavorable outcome and 7 had a favorable outcome. The fNIRS-based model predicted 6-month outcome with a balanced accuracy of 81.3% (sensitivity&#x2009;=&#x2009;85.7%, specificity&#x2009;=&#x2009;76.9%; p&#x2009;=&#x2009;0.006), outperforming clinical models (balanced accuracy&#x2009;=&#x2009;67.6%; p&#x2009;=&#x2009;0.018). The fNIRS-based model also predicted recovery of behavioral responsiveness (balanced accuracy 78.5%; p&#x2009;=&#x2009;0.008) but not covert awareness (70.4%; p&#x2009;=&#x2009;0.109). Bedside fNIRS provides objective neural measures associated with later functional recovery and behavioral responsiveness in patients with acute brain injury. These findings suggest that fNIRS may capture clinically relevant brain function not detected by conventional assessments. With further validation in larger, multicenter cohorts, such approaches may complement existing methods for early prognostication.

Accurate identification of preoperative lymph node metastasis is essential for planning colon cancer treatment. Computed tomography (CT) is widely used for staging, but its diagnostic performance based on size criteria alone remains unclear. This study aimed to evaluate the diagnostic accuracy of preoperative CT for detecting lymph node metastasis in colon cancer. A systematic search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials was conducted on June 12, 2025. Studies comparing preoperative CT with pathological evaluation and providing 2&#x2009;&#xd7;&#x2009;2 contingency tables were included. Pooled sensitivity and specificity were calculated using a hierarchical summary receiver operating characteristic model and a bivariate random-effects model. Subgroup analyses were performed according to cancer location (colon only vs. colon plus rectal cancer) and diagnostic criteria (size alone vs. size plus morphology). Study quality was assessed using QUADAS-2. Twenty-nine studies involving 5634 patients were included. The pooled sensitivity and specificity of CT for detecting lymph node metastasis were 0.693 (95% CI: 0.636-0.744) and 0.660 (95% CI: 0.581-0.731), respectively, with an area under the curve of 0.727. Meta-regression showed no statistically significant differences in diagnostic performance between colon-only studies and those including rectal cancer (p&#x2009;=&#x2009;0.561 and 0.316), or between size-only and morphologic criteria (p&#x2009;=&#x2009;0.822 and 0.536). CT using size criteria alone for preoperative lymph node staging in colon cancer demonstrated only moderate diagnostic performance. These findings indicate that relying on lymph node size as the primary determinant may be insufficient for reliable clinical decision-making.

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To provide an updated view comparing the perioperative, functional characteristics and oncological outcomes in patients submitted to cTURBT and ERBT for the diagnosis and treatment of NMIBC. A search of major databases, including Medline, Embase, Lilacs, Scopus, Web of Science, NIH, Clinical Trials, and EU Clinical Trials Register, was conducted up to January 2025, adhering to PRISMA guidelines. Only Randomized Controlled Trials (RCTs) were included. The primary endpoints assessed were perioperative complications and oncological outcomes. This study encompasses 16 studies including 2.654 patients. Surgery duration showed a longer time of operation in the ERBT group (MD = 3.09, 95% CI 0.15&#x2012;6.03). Also, less time of catheterisation (MD = -0.54, 95% CI -0.97 &#x2012; -0.11) and shorter length of stay in the ERBT group (MD = -0.83, 95% CI -1.41 &#x2012; -0.25). The total number of perioperative complications was lower in the ERBT group, although no statistically significant difference was shown between groups. Lastly, the ERBT group was associated with less chance of triggering the obturator reflex (OR = 5.44, 95% CI 1.61&#x2012;18.34). Oncological outcomes showed no significant difference between groups. ERBT and cTURBT showed no difference in short-term oncological outcomes. Although ERBT did not reduce overall complication rates, it demonstrated a benefit in reducing the occurrence of the obturator reflex and shorter time of hospitalization. Further randomized controlled trials with long-term follow-up and a broad spectrum of tumor sizes are necessary. More randomized controlled trials are needed, focusing on long-term follow-up and a wider range of tumor sizes.

It is critical to identify factors in the work environment that contribute to physician burnout to foster a professional culture that nurtures wellness. This study examined the prevalence of burnout symptoms among a group of Canadian pediatric undergraduate education leaders and explored how membership in a national community (Paediatric Undergraduate Program Directors of Canada, PUPDOC) may serve as a potential mitigating factor. This mixed-methods study involved a survey and subsequent focus groups of PUPDOC members. Survey comprised questions from the Maslach burnout index (MBI) adapted for the educational context. Data were analyzed using descriptive statistics. A qualitative descriptive approach was selected and focus group transcripts were analyzed using content analysis. Themes were generated that relate to PUPDOC's role in shaping members' educational and academic work. Sixteen members completed the survey (16/23, 70%). On the traditional MBI screen, three of 16 participants scored high-risk for burnout, but none reported high levels of symptoms on the adapted questions. Eighteen members participated in focus groups. Themes were interrelated, and included the significance of a sense of community, strengths and stressors of the job, finding meaning in one's work, opportunities, and legitimacy associated with belonging to a group. Our small group of pediatric undergraduate education leaders demonstrated a relatively low burnout rate compared to published rates in physician colleagues. We propose a sense of community that transcends institutions may help to mitigate burnout. By encouraging membership in such organizations, academic institutional leadership can support resilience and invest in the wellbeing of their education leaders.

In Canada, blood operators permanently defer individuals with a history of malaria to prevent transfusion-transmitted malaria. While protective, this policy raises equity concerns, particularly for individuals requiring frequent transfusions, including those living with sickle cell disease. This study examined public awareness of donor screening criteria, perceived barriers to donation, willingness to donate, and views on potential changes to malaria deferral policies. A mixed-methods community based study was conducted using a national survey. The survey assessed awareness of donor screening criteria, perceived barriers, and willingness to donate before and after anticipated malaria policy changes. Quantitative results were stratified by malaria endemicity (high, moderate, and low region groups). Results are presented as proportions with 95% confidence intervals. Open text responses were analyzed using categorical thematic coding. Overall awareness of donor screening criteria was high at 67.5% (n&#x2009;=&#x2009;385). Across endemicity groups, most participants reported no concerns regarding blood safety if a malaria test were implemented. A small subset of respondents (n&#x2009;=&#x2009;113, 29.3%) expressed concerns, primarily related to testing reliability and blood handling processes. Willingness to donate remained unchanged for under half the respondents, with 38%-44% reporting willingness to donate pre-implementation and post-implementation. Notably, 13%-21% of those unwilling to donate before reported increased willingness to donate. Safety concerns were limited, and malaria screening was not perceived as a barrier to donation. These findings support implementation of malaria nucleic acid testing and removal of lifetime deferral policies, highlighting opportunities to expand donor eligibility while maintaining blood safety.

Artificial intelligence (AI) is increasingly embedded in health systems globally and has the potential to improve efficiency, diagnostic accuracy, and decision support. However, its benefits remain unevenly distributed, particularly in low- and middle-income countries (LMICs). Models developed using datasets from specific populations may perform poorly in other settings, reinforcing structural inequities rather than correcting them. This viewpoint proposes a composite framework, the AI in Healthcare Equity Index (AIHEI), to support measurable assessment of equity in health AI systems. The AIHEI is designed to assess equity across five domains: data representation, algorithmic fairness, transparency and explainability, governance and oversight, and community impact and benefit sharing. By generating a standardised score, the index could enable comparisons across technologies, incentivise improvement, and support regulation, procurement, publication, and funding decisions. Pilots across diverse health domains and geographic settings are needed to assess feasibility, refine domain weighting, and evaluate reliability, reproducibility, and validity. Important challenges include contextual definitions of fairness, data sovereignty, post-deployment monitoring, and the risk of metric gaming. Quantifying equity in health AI is essential to ensure that AI does not create, widen, or exacerbate existing disparities by neglecting underserved populations. A common, objective measure of AI-related health equity can help move the field from ethical aspiration toward measurable accountability, monitoring, and enforcement.

Major depressive disorder (MDD) is heterogeneous in clinical presentation and treatment response. The COORDINATE-MDD consortium identified two magnetic resonance imaging (MRI)-derived neuroanatomical profiles: dimension 1 (D1), with relatively preserved gray and white matter, and dimension 2 (D2), showing widespread reductions aligned with immunometabolic profile. Profiles were associated with distinct responses to selective serotonin reuptake inhibitor (SSRI) antidepressant and placebo (PLA). In this study, we examined electrophysiological correlates of the neuroanatomical profiles and their relationship to treatment outcome. Baseline resting-state, eyes-closed electroencephalography (EEG) was acquired from 237 medication-free participants with MDD who were in a current depressive episode (155 women; mean age [SD] = 37.47 [13.36] years) from CAN-BIND (Canadian Biomarker Integration Network in Depression) (SSRI) and EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) (SSRI or PLA). EEG features included spectral power, frontal alpha asymmetry (FAA), multiscale sample entropy, and intersite phase clustering. Effects of profile (D1 and D2) and clinical outcome (responder, nonresponder; defined as &#x2265;50% symptom improvement) were examined with age, sex, and site as covariates. No significant electrophysiological differences were observed after covariate adjustment. However, among participants who subsequently responded to treatment, D1 showed greater baseline alpha power in frontal and central regions and lower relative delta posteriorly compared with D2. In PLA-treated responders, D2 showed spectral slowing, elevated low-frequency power, reduced gamma, and coarse-scale entropy compared with D1. Baseline FAA was lower in responders than nonresponders, independent of the neuroanatomical profile. EEG differences between MRI-defined neuroanatomical profiles emerged in relation to clinical outcome. D1 was associated with electrophysiological patterns consistent with flexible, globally regulated cortical dynamics in SSRI responders, whereas D2 showed a distinct pattern in PLA responders, indicating partially separable neural mechanisms underlying pharmacological and PLA treatment effects. Depression is a common condition, but people differ in their symptoms, underlying biology, and response to treatment. This makes it difficult to predict which treatments will be most effective for each individual. Previous research from the COORDINATE-MDD consortium identified two brain-based groups of individuals with depression using MRI scans. One group showed relatively preserved brain structure and better response to antidepressant medication, whereas the other showed more widespread structural changes and similar improvement with medication or placebo, suggesting different underlying mechanisms. In this study, we examined whether these groups also differ in brain activity measured using electroencephalography before treatment. No clear differences were seen across all participants. However, among those who later improved, distinct patterns emerged: one group showed more organized and adaptable brain activity patterns and greater response to medication, whereas the other showed slower activity and reduced complexity linked to placebo response. These findings suggest that different biological mechanisms underlie treatment response, supporting more personalized approaches to care.

Piezo2 channels are mechanosensors expressed in dorsal root ganglia and Merkel cells, and involved in proprioception and touch sensation. PIEZO2 pathogenic variants cause rare autosomal dominant and recessive disorders. Dominant forms include distal arthrogryposis type 3, 5, and Marden-Walker syndrome, whereas the recessive form corresponds to distal arthrogryposis with impaired proprioception and touch (DAIPT). Given the rarity of these conditions, additional reports are essential to refine their phenotypic characterization. We conducted a multicenter, retrospective study to identify patients with genetically confirmed PIEZO2-related disorders. We collected clinical data through a standardized assessment. Previously published cases were included when more detailed phenotypic information was available. We identified 44 individuals with a clinical diagnosis of PIEZO2-related disorders. Among them, we selected 42 patients with a confirmed molecular diagnosis. Sixteen of them (10 males and 6 females; median age at diagnosis: 8 years; range 0.9-14) carried biallelic pathogenic PIEZO2 variants. They typically presented with neonatal hypotonia and respiratory distress with feeding difficulties. Distal arthrogryposis was associated with a variable multisystemic involvement, including the musculoskeletal system with scoliosis, hip dislocation and laryngomalacia. Twenty-five patients (11 males and 14 females; median age at diagnosis: 7 years; range 0.3-39 years) carried monoallelic variants, exhibiting a broad phenotypic spectrum. An additional prenatal diagnosis (at 23 weeks of gestation) was reported among heterozygous cases. In our cohort, ten previously unpublished causative variants were identified. A systematic assessment of skeletal muscle involvement revealed a severe myofibrillar disarray in one case. This study provides a comprehensive and systematic phenotypic characterization of patients across the spectrum of PIEZO2-related disorders. Our findings support a clear clinical distinction between recessive and dominant forms. The clinical manifestations extend beyond the peripheral nervous system and the Merkel cells, suggesting a broader PIEZO2 tissue expression during early developmental stages. Dominant PIEZO2-related disorders are heterogeneous, ranging from mild to severe forms. Our study also suggests that many patients exhibit a respiratory involvement, emphasizing the need for regular respiratory follow-up in the long-term clinical management of both dominant and recessive forms.

Shared Decision-Making (SDM) is a communication process that supports clinical decision-making by leveraging veterinary expertise and client knowledge to create feasible care plans and has been identified to have an important role in practicing the Spectrum of Care (SpoC). One decision-making aid, the Value Matrix (VM), has been developed to support student veterinarians and practicing veterinary professionals in the practice of SDM. Involving one-on-one semistructured interviews, the present study explored veterinary clients' and veterinarians' perceptions of the VM. Interviews were conducted with 21 veterinary clients and 14 veterinarians. Content analysis was performed on verbatim transcripts. All client participants (CPs) (21/21, 100%) and most veterinarian participants (VPs) (12/14, 86%) had an immediate positive reaction to a video example of the VM used in a clinical context. All participants identified advantages to using the VM in support of veterinarian-client decision-making, including the ability to involve the client, address client and patient barriers, and assist clients with information recall and understanding. CPs and VPs described some potential challenges, most commonly, fitting discussion of the VM within allotted appointment times. CPs and VPs identified that the VM would be best utilized in complex cases in which preference-sensitive decisions existed. Overall, findings suggest that the VM offers a valuable communication aid for practicing veterinary professionals to consider when engaging clients in SDM. Furthermore, with a recognized need to support teaching SDM as part of educating veterinary professionals, findings suggest the VM also offers a potential educational resource to support the teaching of SDM to student veterinarians.

The gut microbiota is a critical determinant of both therapeutic efficacy and immune-related toxicity during cancer immunotherapy with immune checkpoint inhibitors (ICIs). Fecal microbiota transplantation (FMT) has emerged as a strategy to introduce beneficial microbial functions, yet clinical outcomes remain variable. In this Review, we integrate evidence from recent clinical trials combining FMT with ICIs in a mechanism-based framework for understanding this variability and to guide safer clinical applications. We discuss how specific microbial functional programs can either buffer or lower thresholds for immune dysregulation and outline implications for donor selection, longitudinal monitoring, and trial design in oncology.

Conducting systematic reviews of prognostic factors is challenging, especially in the presence of abundant evidence. In this paper, we describe challenges encountered and lessons learned from our experience in conducting a systematic review and meta-analysis for prognostic biomarkers used in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Throughout the process of conducting the systematic review, we drafted the challenges encountered at each step, tackled potential solutions and insights for the addressed challenges. We then met as a group to discuss whether any further individual issues needed to be added, and what aspects would have made the process easier. Despite a few issues in multiple steps of the process, the authors thought the most challenging step was data analysis and interpretation, mainly due to the variability in how the data was reported. Other challenges were related to screening and extraction of data due to the large number of studies that were not primarily prognostic studies but included valuable data to this review. Using the worked example of a prognostic systematic review and meta-analysis for biomarkers used in ADPKD, we believe the challenges mentioned and tips provided will make the process easier for researchers conducting future prognostic systematic reviews focusing on prognostic factors.