High-risk Patients Research Articles

Internal Fixation With Cannulated Screws for Stable Femoral Neck Fractures in High-Risk Patients: Good Clinical Outcomes and Evaluation of Postoperative Complications

Internal Fixation With Cannulated Screws for Stable Femoral Neck Fractures in High-Risk Patients: Good Clinical Outcomes and Evaluation of Postoperative Complications

Preventing cardiovascular disease in at-risk patients: Results of a pilot behavioural health programme in general practice

Background The ‘High-Risk Prevention Programme’ (HRPP) involved a six-week health behaviour change programme based in general practices and aimed to address cardiovascular disease (CVD) risk in disadvantaged Irish communities. Objectives This pilot study aimed to establish the HRPP’s likely effectiveness and acceptability to inform the development of a future definitive trial. Methods The HRPP was conducted at six general practices in disadvantaged areas in the Ireland East region. Patients with high CVD risk were recruited by participating practices and were allocated to either a General Practice Nurse (GPN) or Health Promotion Professional (HPP) led programme focusing on positive health behavioural change. Baseline and 12-month follow-up data were collected to capture the HRPP’s likely effectiveness in promoting health outcomes and health behavioural change. Results The HRPP programme was completed by 270 patients. Out of these 270 patients, 245 (90.74%) completed baseline assessments, and 176 (65.19%) completed follow-up assessments at 12 months. Baseline data indicated a high level of CVD risk among patients and follow-up demonstrated positive change in several areas, especially weight (−1.95 kg, p < 0.001), BMI (−0.72, p < 0.001), exercise during the last week ( p <0.001), and consumption of healthy fats in the HPP group (+60%, p < 0.001). Conclusion The HRPP was a much-needed pilot intervention, and positive results were seen in both GPN and HPP arms, especially with regards to weight loss, exercise, and dietary improvements. Future definitive trials of the HRPP are likely to be effective and acceptable in terms of combatting these issues among high-risk patients.

Therapy-Related Myeloid Neoplasms: Complex Interactions among Cytotoxic Therapies, Genetic Factors, and Aberrant Microenvironment.

Therapy-related myeloid neoplasm (t-MN), characterized by its association with prior exposure to cytotoxic therapy, remains poorly understood and is a major impediment to long-term survival even in the era of novel targeted therapies due to its aggressive nature and treatment resistance. Previously, cytotoxic therapy-induced genomic changes in hematopoietic stem cells were considered sine qua non in pathogenesis; however, recent research demonstrates a complex interaction between acquired and hereditary genetic predispositions, along with a profoundly senescent bone marrow (BM) microenvironment. We review emerging data on t-MN risk factors and explore the intricate interplay among clonal hematopoiesis, genetic predisposition, and the abnormal BM microenvironment. Significance: t-MN represents a poorly understood blood cancer with extremely poor survival and no effective therapies. We provide a comprehensive review of recent preclinical research highlighting complex interaction among emerging therapies, hereditary and acquired genetic factors, and BM microenvironment. Understanding the risk factors associated with t-MN is crucial for clinicians, molecular pathologists, and cancer biologists to anticipate and potentially reduce its incidence in the future. Moreover, better understanding of the molecular pathogenesis of t-MN may enable preemptive screening and even intervention in high-risk patients.

Hypercholesterolemia and Alzheimer's Disease: Unraveling the Connection and Assessing the Efficacy of Lipid-Lowering Therapies.

This article examines the relationship between cholesterol levels and Alzheimer's disease (AD), beginning with the early observation that individuals who died from heart attacks often had brain amyloid deposition. Subsequent animal model research proved that high cholesterol could hasten amyloid accumulation. In contrast, cholesterol-lowering treatments appeared to counteract this effect. Human autopsy studies reinforced the cholesterol-AD connection, revealing that higher cholesterol levels during midlife significantly correlated with higher brain amyloid pathology. This effect was especially pronounced in individuals aged 40 to 55. Epidemiological data supported animal research and human tissue observations and suggested that managing cholesterol levels in midlife could reduce the risk of developing AD. We analyze the main observational studies and clinical trials on the efficacy of statins. While observational data often suggest a potential protective effect against AD, clinical trials have not consistently shown benefit. The failure of these trials to demonstrate a clear advantage is partially attributed to multiple factors, including the timing of statin therapy, the type of statin and the appropriate selection of patients for treatment. Many studies failed to target individuals who might benefit most from early intervention, such as high-risk patients like APOE4 carriers. The review addresses how cholesterol is implicated in AD through various biological pathways, the potential preventive role of cholesterol management as suggested by observational studies, and the difficulties encountered in clinical trials, particularly related to statin use. The paper highlights the need to explore alternate therapeutic targets and mechanisms that escape statin intervention.

Economics of risk stratification for skin cancer screening in solid organ transplant recipients

Background: Solid organ transplant recipients (SOTRs) have different risks of developing skin cancer depending on patient characteristics. However, there is currently no widely used tool to stratify skin cancer risk in these patients. The Skin and Ultraviolet Neoplasia Transplant Risk Assessment Calculator (SUNTRAC) is an attempt to stratify skin cancer risk in SOTRs and guide screening recommendations for those patients. Materials and methods: It was assumed that the 2022 solid organ transplant population in the United States would follow the same distribution of skin cancer risk as the population in the study that led to the development of the SUNTRAC. The total number of skin cancer screening visits and the total cost of those visits over 10 years were determined utilizing the screening recommendations in the SUNTRAC. Results: If all SOTRs received yearly skin cancer screens, 428,870 office visits would be conducted over 10 years for a total cost of $94,780,270. If the SUNTRAC were utilized, 336,666 office visits would be conducted for a 10-year cost of $74,403,186. Conclusions: Utilizing the SUNTRAC to guide skin cancer screening recommendations in SOTRs has the potential to minimize over-screening and lower the total cost of skin cancer screening visits for SOTRs. Initial studies into the applicability of the SUNTRAC have found similar risk distribution in different populations of SOTRs. Utilizing this model to guide skin cancer screening recommendations will better allocate resources to the highest risk patients while also avoiding unnecessary health care costs.

Design and development of a machine-learning-driven opioid overdose risk prediction tool integrated in electronic health records in primary care settings

BackgroundIntegrating advanced machine-learning (ML) algorithms into clinical practice is challenging and requires interdisciplinary collaboration to develop transparent, interpretable, and ethically sound clinical decision support (CDS) tools. We aimed to design a ML-driven CDS tool to predict opioid overdose risk and gather feedback for its integration into the University of Florida Health (UFHealth) electronic health record (EHR) system.MethodsWe used user-centered design methods to integrate the ML algorithm into the EHR system. The backend and UI design sub-teams collaborated closely, both informed by user feedback sessions. We conducted seven user feedback sessions with five UF Health primary care physicians (PCPs) to explore aspects of CDS tools, including workflow, risk display, and risk mitigation strategies. After customizing the tool based on PCPs’ feedback, we held two rounds of one-on-one usability testing sessions with 8 additional PCPs to gather feedback on prototype alerts. These sessions informed iterative UI design and backend processes, including alert frequency and reappearance circumstances.ResultsThe backend process development identified needs and requirements from our team, information technology, UFHealth, and PCPs. Thirteen PCPs (male = 62%, White = 85%) participated across 7 user feedback sessions and 8 usability testing sessions. During the user feedback sessions, PCPs (n = 5) identified flaws such as the term “high risk” of overdose potentially leading to unintended consequences (e.g., immediate addiction services referrals), offered suggestions, and expressed trust in the tool. In the first usability testing session, PCPs (n = 4) emphasized the need for natural risk presentation (e.g., 1 in 200) and suggested displaying the alert multiple times yearly for at-risk patients. Another 4 PCPs in the second usability testing session valued the UFHealth-specific alert for managing new or unfamiliar patients, expressed concerns about PCPs’ workload when prescribing to high-risk patients, and recommended incorporating the details page into training sessions to enhance usability.ConclusionsThe final backend process for our CDS alert aligns with PCP needs and UFHealth standards. Integrating feedback from PCPs in the early development phase of our ML-driven CDS tool helped identify barriers and facilitators in the CDS integration process. This collaborative approach yielded a refined prototype aimed at minimizing unintended consequences and enhancing usability.

Variable-RBE-induced NTCP predictions for various side-effects following proton therapy for brain tumors – Identification of high-risk patients and risk mitigation

Background and purposeDisregarding the increase of relative biological effectiveness (RBE) may raise the risk of acute and late adverse events after proton beam therapy (PBT). This study aims to explore the relationship between variable RBE (above 1.1)-induced normal tissue complication probabilities (NTCP) and patient-specific factors, identify patients at high risk of RBE-induced NTCP increase, and assess risk mitigation by incorporating RBE variability into treatment planning. Materials and methodsWe retrospectively analyzed 105 primary brain tumor patients treated with PBT (RBE = 1.1). We calculated differences in estimated NTCP (ΔNTCP) using a variable RBE-weighted dose (DRBE, Wedenberg model) and a constant RBE-weighted dose (DRBE=1.1), across 16 NTCP models. These differences were correlated with patient-specific characteristics. Based on ΔNTCP, patients were classified as high risk (32 %) or low risk (68 %) for adverse events due to RBE-induced NTCP. This classification was compared with alternative classifications based on (a) relevant patient-specific characteristics, (b) DRBE=1.1, and (c) the difference between DRBE and DRBE=1.1 (ΔD), assessing the balanced accuracy. The potential to reduce RBE-induced NTCP through track-end and linear energy transfer (LET) optimization was evaluated in six example patients. ResultsUsing a variable RBE instead of a constant one resulted in NTCP increases (up to 32 percentage points). Variable-RBE-induced NTCP increases were strongly negatively correlated with the distance between the clinical target volume (CTV) and the organ at risk (OAR) for most side-effects, and positively correlated with CTV volume for certain side-effects. High increases were associated with (a) specific patient factors, particularly the proximity of the CTV to OARs, (b) DRBE=1.1, and (c) ΔD, with a balanced accuracy of 0.88, 0.94, and 0.86, respectively. Optimization of track-ends and LET considerably reduced NTCP values, achieving a mean reduction of 31 % for optimized OARs. ConclusionThe risk of variable-RBE-induced NTCP strongly depends on patient-specific factors and the considered side-effect. A small distance between the tumor and OARs notably increases the risk. Integrating biologically-guided objectives into treatment planning can effectively mitigate the risk.

Evolving Practice and Outcomes in Grade 2 Glioma: Real-World Data from a Multi-Institutional Registry.

Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016-December 2019 (TP1) and January 2020-December 2022 (TP2), were defined. Survival was estimated using the Kaplan-Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusions: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management.

Impact of ticagrelor with or without aspirin on total and recurrent bleeding and ischemic events after percutaneous coronary intervention: A sub-study of the TWILIGHT trial.

In standard time-to-first event analysis, early aspirin discontinuation followed by ticagrelor monotherapy has been shown to reduce bleeding without increasing ischemic complications compared with ticagrelor plus aspirin after percutaneous coronary intervention (PCI). We evaluated whether these treatment effects are preserved when recurrent events are considered. In this TWILIGHT trial post hoc analysis, we assessed the effects of ticagrelor monotherapy on the total number of events that occurred over the 12-month follow-up among 7 119 high-risk patients randomized to aspirin or placebo in addition to ticagrelor at 3 months post-PCI if event-free and adherent to treatment. There were 391 patients with at least one Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (primary endpoint). Of those, 28 (7.2%) had a recurrent event. The total number of BARC 2, 3, or 5 bleeding events were 148 in the ticagrelor monotherapy arm compared with 278 with ticagrelor plus aspirin arm (p<0.001). Among 272 patients with at least one key secondary ischemic endpoint (all-cause death, myocardial infarction, or stroke), 37 (13.6%) sustained a recurrent event. Total ischemic events were similar (155vs 159) in the two groups. Among selected high-risk patients who underwent PCI and completed 3 months of dual antiplatelet therapy followed by ticagrelor with or without aspirin, recurrent bleeding was less common than recurrent ischemic events over 12 months. Analysis of total events indicates that ticagrelor monotherapy continues to be more effective than ticagrelor plus aspirin in reducing bleeding without a signal of ischemic harm.

Comparative analysis of single versus tandem autologous stem cell transplantation in patients with multiple myeloma in Korea: the KMM2102 study

Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients.

Comparison of abiraterone, enzalutamide, and apalutamide for metastatic hormone-sensitive prostate cancer: A multicenter study.

We aimed to assess the differential efficacy and safety of androgen receptor pathway inhibitors (ARPI), such as abiraterone, enzalutamide, and apalutamide, in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a real-world practice setting. We retrospectively reviewed the records of consequent 668 patients with mHSPC treated with ARPI plus androgen deprivation therapy between September 2015 and December 2023. Based on the LATITUDE criteria, the comparison among abiraterone, enzalutamide, and apalutamide was exclusively conducted in high-risk patients. Prostate-specific antigen (PSA) responses such as the achievement of 95% and 99% PSA decline, overall survival (OS), cancer-specific survival (CSS), time to castration-resistant prostate cancer (CRPC), and the incidence of adverse events (AEs) were compared. All two-group comparisons relied on propensity score matching (PSM) to minimize the effect on possible confounders. In total, 297 patients with high-risk mHSPC treated with abiraterone, 127 with enzalutamide, and 142 with apalutamide were compared. There were no differences in time to CRPC (p = 0.13), OS (p = 0.7), and CSS (p = 0.5) among the three ARPIs. No differences were observed in the achievement rates for 95% PSA decline at 3 months among the three ARPIs, while abiraterone was significantly better in 99% PSA decline achievement compared to apalutamide (72% vs. 57%, p = 0.003). The aforementioned oncologic outcomes were sustained even when performing PSM analyzes. Although skin rash for APA (34%) was the highest incidence of AEs, there were no differences in the rates of severe AEs across the three ARPIs. Enzalutamide resulted in the lowest treatment discontinuation rates (10%) other than disease progression compared to the other regimens. Abiraterone, enzalutamide, and apalutamide have comparable oncologic outcomes in terms of OS, CSS, and time to CRPC in patients with high-risk mHSPC. Our data on differential treatment discontinuation rates, PSA response, and AE profiles can help guide clinical decision-making.

Modified cardiopulmonary bypass circuit for transcatheter aortic valve implantation and emergent cardiac surgery.

Transcatheter aortic valve implantation (TAVI) has revolutionized the treatment of severe aortic stenosis in high-risk patients, offering a minimally invasive alternative to open-heart surgery. However, complications such as hemodynamic instability may require mechanical circulatory support. In some cases, emergent cardiac surgery may be required, necessitating a swift transition to cardiopulmonary bypass (CPB). We modified the CPB circuit allowing for circulatory support and easy transition to CPB. No bleeding or vascular complications were observed. The modified CPB circuit minimizes hemodynamic disruptions and allows for postoperative ECMO support.

The Utility of Multitarget Stool DNA Testing for Colorectal Cancer Screening After a Normal Colonoscopy.

Multitarget stool DNA (MT-sDNA) tests (here, Cologuard®) are currently used in average-risk patients as a primary method of screening for colorectal cancer. However, MT-sDNA testing has also been used in patients who previously underwent colonoscopy who wish to avoid repeat colonoscopy. Here, in a large primary care practice setting, our aim was to evaluate the diagnostic performance of MT-sDNA testing in patients with a previously normal colonoscopy. This retrospective cohort study included 5827 patients from 35 different primary locations in South Carolina. Patients aged 45 and above with a previously documented normal, high-quality colonoscopy prior to the MT-sDNA test date were included. High-risk patients and those with a previous negative MT-sDNA result were excluded. Of 5827 ordered MT-sDNA tests, 248 patients had a prior normal colonoscopy. The average time from initial colonoscopy to MT-sDNA testing was 7.3years. Of the 63 patients who had a positive MT-sDNA test, 41 patients (65%) completed follow-up colonoscopy and 40 patients had complete colonoscopy data. Of these 40 patients, 12 patients (30%) had advanced adenomas and none had colorectal cancer. Compared to patients without a previous colonoscopy, patients with prior colonoscopies had fewer adenomas of all types (1.6 vs 2.4) and fewer advanced adenomas (1.4 vs 2.0). Patients with a previously negative colonoscopy and subsequent positive MT-sDNA test were found to have a high rate of advanced adenomas on follow-up colonoscopy (30%). Thus, in patients with a previously negative colonoscopy, MT-sDNA testing may be a reasonable alternative screening option.

Implementation strategies to improve adoption of unmet social needs screening and referrals in care management using enabling technologies: study protocol for a cluster randomized trial.

Background Adverse social determinants of health contribute to health inequities. Practice guidelines now recommend incorporating patient unmet social needs into patient care, and payors increasingly reimburse for screening and providing related referrals to community organizations. Emergent electronic health record (EHR)-based tools can enable clinical-community linkages, but their adoption commonly faces workflow and infrastructure barriers. Targeted implementation support such as training, championship, practice facilitation, and audit and feedback, can enhance such tools' adoption, but no prior research has assessed such strategies' impact on the adoption of 'enabling technologies' supporting clinical-community linkages. This study will test whether providing targeted implementation support to safety-net primary care health center care management teams improves the sustained adoption of EHR-based enabling technologies used to 1) screen for social needs and 2) link patients to community organizations. Methods Formative evaluation of barriers and facilitators to adopting EHR-enabled social needs referrals and ascertainment of services received will include semi-structured interviews and a 'guided tour' of enabling technology used by care managers serving patients with complex health and/or social needs. A modified Delphi process conducted with care management staff and subject matter experts will then inform the development of an intervention targeting adoption of social risk EHR-enabled tools. The intervention will be piloted in three health centers, refined, then tested in a pragmatic stepped-wedge cluster-randomized trial in 20 health centers (five wedges of four health centers) that provide care management to high-risk patients with social needs. Discussion This study is among the first to evaluate an intervention designed to support care management teams' adoption of enabling technologies to increase clinical-community linkages. It was funded in September 2023 by the National Institute of Nursing Research. Formative activities will take place from January to June 2024, the intervention will be developed in July-December 2024, the pilot study will be conducted from January-March 2025, and the cluster-randomized trial will occur from July 2025 -September 2026. Study data will be analyzed and results disseminated in 2027-2028. Study results have the potential to improve clinical-community linkages and in so doing to advance health equity. Trial registration Clinicaltrials.gov registration # NCT06489002. Registered July 5, 2024, https//clinicaltrials.gov/study/NCT06489002?term=NCT06489002&rank=1.

Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients.

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

The Saudi thoracic society guidelines for vaccinations in adult patients with chronic respiratory diseases

Abstract: Adult patients with chronic respiratory diseases (CRDs) are considered high risk group who are more likely to experience worse clinical outcomes if they acquire viral or bacterial infections. Vaccination is the best preventive tool to reduce the risk of infection and disease occurrence and to reduce the level of severity of complications associated with the various vaccine-preventable infections. These guidelines were developed by the Saudi Thoracic Society task force to emphasize the critical importance of improving the vaccine coverage rates in adult patients with CRD. They are intended to serve as a reference for healthcare practitioners managing CRD patients. The guidelines aimed to review the current knowledge related to vaccination efficacy in adult patients with CRD, based on the recent evidence and recommendations. Integrating the administration of the recommended vaccines in routine healthcare, such as during outpatient visits or before hospital discharge, is crucial for improving the vaccination rates in high-risk patients. The key strategies to address this public health priority include simplifying vaccination guidelines to enhance their accessibility and implementation by healthcare providers, increasing awareness in both the patients and healthcare providers that vaccines are not only intended for children. Additional strategies include maintaining continuous surveillance and advance research to discover novel vaccines. This approach aims to expand the range of preventable diseases and improve overall health and well-being. Vaccine hesitancy remains a significant challenge that necessitates a clear understanding of the community concerns. Providing appropriate education and communication, as well as addressing these concerns, are the crucial steps toward improving vaccine acceptance and uptake. By implementing these guidelines and multifaceted strategies, healthcare systems can optimize vaccine coverage and protection for patients with CRD, reduce the burden of vaccine-preventable complications, and improve the clinical outcomes in this vulnerable population.

Acceptability of dried blood spot collection by primary caregivers of Filipino patients with maple syrup urine disease (MSUD) and phenylketonuria (PKU).

MSUD and PKU require lifetime management hence, regular monitoring of amino acid levels is needed to achieve good metabolic control. Ideally, plasma amino acid analysis (PLAA) is used to monitor concentrations but is expensive and not widely available in local laboratories. The newborn screening program in the Philippines uses dried blood spot (DBS) analysis as an alternative where only trained healthcare providers are allowed to perform the collection at selected facilities. With the increasing number of patients, DBS monitoring has been noted to be delayed due to multiple factors. This issue became even more evident during the COVID-19 pandemic where high-risk patients need to travel outside for blood collection. The study used a cross-sectional study design to determine the primary caregivers' perspective on DBS self-sampling for patients with MSUD and PKU and the acceptability of the samples collected. This was done through a series of collection training, pre-/post- surveys, and 10-item questionnaire, and an in-depth 1-on-1 interview for thematic analysis. The acceptability of samples was processed and evaluated by the newborn screening laboratory. At-home DBS collection by primary caregivers was found to be acceptable. The provision of knowledge and routine collection training by the medical team aids in the increase of sample acceptability as well as a source of empowerment in being equipped to take care of their child. It is highly recommended that DBS samples collected by caregivers be considered acceptable for more time and cost-saving monitoring of the patients' metabolites. This practice also promotes timely and appropriate management which can lead to better patient health outcomes.

Clinical-applied anatomy of the carpal tunnel regarding mini-invasive carpal tunnel release.

Carpal tunnel release is a widely performed procedure. Despite a high success rate, iatrogenic neurovascular injuries can occur which lead to a painful and unsatisfying outcome. This study conducted a detailed examination of the anatomy of the carpal tunnel and the proximity of neurovascular structures that are particularly susceptible to injury, especially in the context of minimally invasive carpal tunnel release procedures. The anatomy of the carpal tunnel of 104 wrists of 52 body donors was examined. The precise anatomical location and the presence of variations were recorded for the median nerve, ulnar nerve, ulnar artery and Berrettini branch. The distance between the median nerve, the ulnar artery, the ulnar nerve, and the Berrettini branch was measured in a proximo-distal and radio-ulnar direction in relation to the distal ulnar end of the carpal tunnel. The authors identified four main dangerous anatomical situations. (1) A proximal separation of the Long-Finger/Ring-Finger branch of the median nerve together with a narrow safe-zone; (2) an ulnar take-off of the recurrent muscle branch of the median nerve with a close radio-ulnar distance to the distal ulnar end of carpal tunnel; (3) an ulnar arterial arch lying close to the transverse carpal ligament; and (4) a proximal Berrettini branch also lying close to the latter. All situations are illustrated by photographs. Additionally, the authors present a sonographic carpal tunnel assessment protocol in order to reduce the risk of injury of any neurovascular structure in the proximity of the carpal tunnel. Certain patients may inherently face an increased risk of neurovascular injuries during minimally invasive carpal tunnel releases due to their anatomical variations. Four potentially risky scenarios were clearly illustrated. Consequently, one may consider conducting a preoperative ultrasound assessment of neurovascular structures at risk, when endoscopic or ultrasound-guided tunnel release are planned. In high-risk patients, open surgery should be preferred. II.

Identification of immune-related gene signature model for predicting lung cancer survival and response to immunotherapy.

Studies have shown that immune-related genes play a crucial role in tumor development and treatment. However, the specific roles and potential value of these genes in lung cancer patients are still not fully understood. Therefore, this study aims to establish a novel risk model based on immune-related genes for evaluating the prognostic risk and response to immune therapy in lung cancer patients. Gene expression and clinical data of lung cancer patients were retrieved from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, while immune-related genes were obtained from the ImmPort database. A risk signature model was developed using univariate Cox analysis and LASSO regression analysis. The prognostic value of the model and its response to immunotherapy were analyzed by survival analysis, immune infiltration analysis and immunotherapy response analysis. We have developed a risk signature model based on eight key immune-related genes, which can classify patients into high-risk and low-risk groups. The prognosis of the high-risk group was significantly lower than that of the low-risk group and was validated in multiple GEO datasets. The mutation frequency was lower in the low-risk group compared to the high-risk group (TP53: 55% vs 65%; TTN: 52% vs 60%; CSMD3: 34% vs 45%). Futhermore, CD274 expression was lower in the low-risk patients, and the high-risk patients in the IMvigor210 cohort had lower survival. Immune infiltration analyses showed that the high-risk group was negatively correlated with the infiltration level of B cells, CD4+ T cells, and NK cells. Importantly, patients in the low-risk group exhibit significantly lower TIDE scores, suggesting that they are more responsive to immunotherapy. Our study has established a novel and robust immune-related gene risk model that can assist in evaluating the prognostic risk and immune therapy response of lung cancer patients.

Failure to Rescue Female Patients Undergoing High-Risk Surgery

Female patients have higher mortality rates after high-risk surgery than male patients. It is unknown whether this mortality gap is due to different rates of postoperative complications or if complications are addressed differently by sex, causing complications to lead to death-so-called failure to rescue. To evaluate sex differences in failure to rescue across high-risk surgical procedures. This retrospective cohort study was conducted using data from Medicare beneficiaries from October 2015 to February 2020 who underwent high-risk vascular or cardiac surgical procedures, including abdominal aortic aneurysm repair, coronary artery bypass grafting, aortic valve replacement, and mitral valve replacement or repair. Data analysis was performed from August 2023 to March 2024. The primary exposure was patient sex. The primary outcomes were risk-adjusted rates of complications, 30-day mortality, and failure to rescue, which was defined as a death occurring after a serious complication. Categorical variables are presented as frequencies and proportions and compared using χ2 analysis. Continuous variables were tested for normality and compared using a t test. A total of 863 305 Medicare beneficiaries were included in this study cohort, of whom 304 176 (35.2%) were female. Mean (SD) age was slightly higher in female patients (74.8 [9.3] years) than male patients (73.4 [8.5] years), and female patients had more comorbidities than male patients (≥2 Elixhauser comorbidities, female: 262 809 [86.4%] vs male: 465 231 [83.2%]). Female patients were more likely to receive care at large hospitals and hospitals with a higher surgical case volume. Overall, female and male patients had similar rates of complications (female: 14.98% vs male: 14.37%; adjusted relative risk [aRR], 1.04; 95% CI, 1.03-1.05; P < .001). However, female patients had higher rates of 30-day mortality (female: 4.22% vs male: 3.34%; aRR, 1.26; 95% CI, 1.23-1.29; P < .001) and higher rates of failure to rescue (female: 10.71% vs male: 8.58%; aRR, 1.25; 95% CI, 1.22-1.28; P < .001). A similar pattern was observed when stratified by each procedure. In this cohort study among Medicare beneficiaries undergoing high-risk surgery, male and female patients experienced similar rates of serious complications, but female patients with complications were more likely to die. In other words, clinicians fail to rescue female patients with complications after high-risk surgery more often than male patients. Improving the recognition and management of female patients' complications postoperatively may narrow the sex disparity after high-risk surgery.