Hydrology, vegetation, and soil properties as key drivers of soil organic carbon in coastal wetlands: A high-resolution study.

Coastal wetlands are important blue carbon ecosystems that play a significant role in the global carbon cycle. However, there is insufficient understanding of the variations in soil organic carbon (SOC) stocks and the mechanisms driving these ecosystems. Here we analyze a comprehensive multi-source dataset of SOC in topsoil (0-20 cm) and subsoil (20-100 cm) across 31 coastal wetlands in China to identify the factors influencing their distribution. Structural equation models (SEMs) reveal that hydrology has the greatest overall effect on SOC in both soil layers, followed by vegetation, soil properties, and climate. Notably, the mechanisms driving SOC density differ between the two layers. In topsoil, vegetation type and productivity directly impact carbon density as primary sources of carbon input, while hydrology, primarily through seawater salinity, exerts the largest indirect influence. Conversely, in subsoil, hydrology has the strongest direct effect on SOC, with seawater salinity also influencing SOC indirectly through soil and vegetation mediation. Soil properties, particularly pH, negatively affect carbon accumulation, while climate influences SOC indirectly via its effects on vegetation and soil, with a diminishing impact at greater depths. Using Random Forest, we generate high-resolution maps (90 m × 90 m) of topsoil and subsoil carbon density (R 2 of 0.53 and 0.62, respectively), providing the most detailed spatial distribution of SOC in Chinese coastal wetlands to date. Based on these maps, we estimate that SOC storage to a depth of 1 m in Chinese coastal wetlands totals 74.58 ± 3.85 Tg C, with subsoil carbon storage being 2.5 times greater than that in topsoil. These findings provide important insights into mechanism on driving spatial pattern of blue carbon and effective ways to assess carbon status on a national scale, thus contributing to the advancement of global blue carbon monitoring and management.

Effect of automated identification of antimicrobial stewardship opportunities for suspected urinary tract infections.

Objective: We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention. Design: Retrospective before-and-after study. Setting: Tertiary and quaternary care academic medical center. Patients: Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods. Methods: We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020-12/2020) and post-BPA (04/15/2021-04/30/2022) periods. Results: 774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18-65) in the pre-BPA group compared to 16 hours (IQR 2-34) in the post-BPA group (P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source. Conclusions: Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Mortality After Multivessel Revascularization in Patients With Diabetes and Acute Coronary Syndromes.

Background: The optimal revascularization strategy in patients with diabetes and multivessel disease in the setting of a non-ST-segment elevation myocardial infarction (NSTEMI) is unknown. Objectives: The purpose of this study was to compare all-cause mortality between coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) among patients with diabetes and NSTEMI. Methods: All patients with diabetes and multivessel disease admitted for NSTEMI in Ontario, Canada, between April 2009 and March 2020 were included. Those with previous CABG, PCI in the previous 90 days, or shock were excluded. The primary outcome was all-cause mortality. Propensity score matching was used to account for confounding. Patients who had a cardiac surgeon consultation and then received PCI were classified as being potentially ineligible for CABG. Results: The cohort included 4,649 CABG and 6,760 PCI patients (mean age: 67.8 ± 11.5 years; 70.4% males), resulting in 2,385 matched pairs. CABG was associated with reduced all-cause mortality compared to PCI over a median follow-up of 5.5 years (5-year estimates: 23.4% vs 26.5%; HR: 0.89; 95% CI: 0.80-0.98; P = 0.021). However, no significant differences in mortality were observed between CABG and PCI patients without a surgical consultation (2,130 pairs; HR: 0.97; 95% CI: 0.86-1.08), while CABG was associated with reduced mortality when compared against PCI patients who had received a surgical consultation (388 pairs; HR: 0.72; 95% CI: 0.58-0.88; P = 0.002). Conclusions: While CABG was associated with reduced all-cause mortality compared to multivessel PCI in patients with diabetes and NSTEMI, CABG benefit was seen only against PCI patients potentially ineligible for CABG after receiving a preprocedure surgical consultation.

Quantitative MRI biomarker for classification of clinically significant prostate cancer: Calibration for reproducibility across echo times.

PURPOSE: The purpose of the present study is to develop a calibration method to account for differences in echo times (TE) and facilitate the use of restriction spectrum imaging restriction score (RSIrs) as a quantitative biomarker for the detection of clinically significant prostate cancer (csPCa). METHODS: This study included 197 consecutive patients who underwent MRI and biopsy examination; 97 were diagnosed with csPCa (grade group ≥ 2). RSI data were acquired three times during the same session: twice at minimum TE ~75 ms and once at TE = 90 ms (TEmin1, TEmin2, and TE90, respectively). A linear regression model was determined to match the C-maps of TE90 to the reference C-maps of TEmin1 within the interval ranging from 95th to 99th percentile of signal intensity within the prostate. RSIrs comparisons were made at the 98th percentile within each patient's prostate. We compared RSIrs from calibrated TE90 (RSIrsTE90corr) and uncorrected TE90 (RSIrsTE90) to RSIrs from reference TEmin1 (RSIrsTEmin1) and repeated TEmin2 (RSIrsTEmin2). Calibration performance was evaluated with sensitivity, specificity and area under the ROC curve (AUC). RESULTS: Scaling factors for C1, C2, C3, and C4 were estimated as 1.68, 1.33, 1.02, and 1.13, respectively. In non-csPCa cases, the 98th percentile of RSIrsTEmin2 and RSIrsTEmin1 differed by 0.27 ± 0.86SI (mean ± standard deviation), whereas RSIrsTE90 differed from RSIrsTEmin1 by 1.82 ± 1.20SI. After calibration, this bias was reduced to -0.51 ± 1.21SI, representing a 72% reduction in absolute error. For patients with csPCa, the difference was 0.54 ± 1.98SI between RSIrsTEmin2 and RSIrsTEmin1 and 2.28 ± 2.06SI between RSIrsTE90 and RSIrsTEmin1. After calibration, the mean difference decreased to -1.03SI, a 55% reduction in absolute error. At the Youden index for patient-level classification of csPCa (8.94SI), RSIrsTEmin1 has a sensitivity of 66% and a specificity of 72%. CONCLUSIONS: The proposed linear calibration method produces similar quantitative biomarker values for acquisitions with different TE, reducing TE-induced error by 72% and 55% for non-csPCa and csPCa, respectively.

Target trial emulation using cohort studies: estimating the effect of antihypertensive medication initiation on incident dementia.

BACKGROUND: Observational studies link high midlife systolic blood pressure to increased dementia risk. However, synthesis of evidence from randomized controlled trials has not definitively demonstrated that antihypertensive medication use reduces dementia risk. Here, we emulate target trials of antihypertensive medication initiation on incident dementia using three cohort studies, with attention to potential violations of necessary assumptions. METHODS: We emulated trials of antihypertensive medication initiation on incident dementia using data from the Atherosclerosis Risk in Communities (ARIC) study, Cardiovascular Health Study (CHS), and Health and Retirement Study (HRS). We used data-driven methods to restrict participants to initiators and non-initiators with overlap in propensity scores and positive control outcomes to look for violations of positivity and exchangeability assumptions. RESULTS: Analyses were limited by the small number of cohort participants who met eligibility criteria. Associations between antihypertensive medication initiation and incident dementia were inconsistent and imprecise (ARIC: HR = 0.30 [0.05, 1.93]; CHS: HR = 0.66 [0.27, 1.64]; HRS: HR = 1.09 [0.75, 1.59]). More stringent propensity score restriction had little effect on findings. Sensitivity analyses using a positive control outcome unexpectedly suggested antihypertensive medication initiation increased risk of coronary heart disease in all three samples. CONCLUSIONS: Positive control outcome analyses suggested substantial residual confounding in effect estimates from our target trials, precluding conclusions about the impact of antihypertensive medication initiation on dementia risk through target trial emulation. Formalized processes for identifying violations of necessary assumptions will strengthen confidence in target trial emulation and avoid inappropriate confidence in emulated trial results.

Correlates of Lifestyle Physical Activity Among Young Arab American Women.

BACKGROUND: Young Arab American women are at risk for cardiovascular disease, but there is limited data on their physical activity (PA) engagement. OBJECTIVES: The aim of this study was to examine the relationship between PA and its correlates in young Arab American women. The objectives of this study were to: (1) describe self-reported lifestyle PA behaviors of young Arab American women and (2) examine the relationship between their self-reported lifestyle PA, device-measured lifestyle PA (combined moderate/vigorous and steps), and potentially associated factors (demographics, physical measures, individual factors, and behavior cognition factors). METHODS: This cross-sectional study was conducted with women 18 to 35 years of age and Arab American (n = 50) in the Midwest Region of the United States. Participants wore ActiGraph GT3X-BT monitors for 7 days; self-report measures included the International Physical Activity Questionnaire, demographics, acculturation, discrimination, religiosity, self-efficacy, and social support. RESULTS: The mean age of participants was 25.5 years (SD: 5.5; range: 18-35). Per ActiGraph, the average daily steps were 5946 (SD: 2783); only 24% met the moderate-intensity PA guidelines. Self-efficacy was significantly associated with increased moderate-to-vigorous PA (B = 0.37; P = .012). CONCLUSION: The average daily steps for the young Arab American women in this study were of low active classification. More than 75% of the women failed to meet the recommended weekly moderate/vigorous PA guidelines. Our study supports the importance of targeting and tailoring PA interventions on young Arab American women who have low self-efficacy for overcoming barriers to lifestyle PA.

Genetic architecture reconciles linkage and association studies of complex traits.

Linkage studies have successfully mapped loci underlying monogenic disorders, but mostly failed when applied to common diseases. Conversely, genome-wide association studies (GWASs) have identified replicable associations between thousands of SNPs and complex traits, yet capture less than half of the total heritability. In the present study we reconcile these two approaches by showing that linkage signals of height and body mass index (BMI) from 119,000 sibling pairs colocalize with GWAS-identified loci. Concordant with polygenicity, we observed the following: a genome-wide inflation of linkage test statistics; that GWAS results predict linkage signals; and that adjusting phenotypes for polygenic scores reduces linkage signals. Finally, we developed a method using recombination rate-stratified, identity-by-descent sharing between siblings to unbiasedly estimate heritability of height (0.76 ± 0.05) and BMI (0.55 ± 0.07). Our results imply that substantial heritability remains unaccounted for by GWAS-identified loci and this residual genetic variation is polygenic and enriched near these loci.

Observed Changes in the Distribution of Colon Cancer Metastasis: A National Cancer Database Review and Institutional Experience.

BACKGROUND: The University of Louisville has observed a near 70% drop in resectable/borderline resectable metastatic colorectal cancer in the past 5 years. The aim of this study was to evaluate the distribution of colon cancer metastasis at diagnosis and at recurrence. PATIENTS AND METHODS: Stage was defined by the American joint committee on cancer (AJCC) eighth edition. Institutional review board approval was granted for post hoc review of stage II and III patients with colon cancer from the University of Louisville prospective hepatic database from 2002 to 2023, as well as for the National cancer database (NCDB) Participant user file (PUF) 2021. The Surveillance epidemiology and end-results (SEER) 22 database was also utilized to corroborate the findings in the NCDB. RESULTS: Between 2018 and 2021 pathological M1a decreased annually (51.9-46.3%), while M1c increased year-over-year (26.6-32.4%) and M1b stayed relatively the same (21.4-21.3%). These differences were significant on chi-squared analysis with a p value of < 0.001. Univariate analysis of the post hoc review between 2017 and 2020 revealed significant differences between stage 4a and 4c in terms of race (p value 0.018), carcinoembryonic antigen (CEA) at diagnosis (p value 0.037), CEA at recurrence (p value 0.012), presence of liver metastasis (p value 0.003), and referral pattern (p value 0.014). Multivariate analysis identified stage 4b as an independent predictor for hepatic metastasis (odds ratio; OR 4.69, p value 0.011). CONCLUSIONS: A significant change in the distribution of colon cancer metastases has occurred at an institutional and national level over the past 3-5 years. Interdisciplinary treatment strategies will have to be modified accordingly.

Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM.

BACKGROUND: Aficamten is a cardiac myosin inhibitor that mitigates left ventricular outflow gradients in obstructive hypertrophic cardiomyopathy (oHCM). The clinical efficacy of aficamten across multiple outcome domains in oHCM has not been fully defined. OBJECTIVES: This responder analysis from the SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM) trial characterizes the clinical impact of aficamten. METHODS: Patients who were symptomatic of oHCM were randomized to aficamten (n = 142) or placebo (n = 140) daily for 24 weeks. Outcomes assessed included the proportion of patients with complete hemodynamic response (rest and Valsalva gradient <30 mm Hg and <50 mm Hg, respectively), relief in limiting symptoms (≥1 improvement in NYHA functional class and/or ≥10-point change in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score), enhanced exercise capacity (≥1.5 mL/kg/min change in peak oxygen uptake), and ≥50% reduction in N-terminal pro-B-type natriuretic peptide. Eligibility for septal reduction therapy was also evaluated. RESULTS: At 24 weeks, patients treated with aficamten vs placebo showed significant improvement in limiting symptoms (71% vs 42%), were more likely to have complete hemodynamic response (68% vs 7%), demonstrated enhanced exercise capacity (47% vs 24%), and showed a decrease ≥50% in N-terminal pro-B-type natriuretic peptide (84% vs 8%) (P ≤ 0.002 for all). An improvement in ≥1 of these outcome measures was achieved in 97% of patients treated with aficamten (vs 59% placebo), including 23% on aficamten who achieved all 4 outcomes compared with none in placebo. Among 32 patients receiving aficamten and 29 patients receiving placebo who were eligible for septal reduction therapy, 28 (88%) from the aficamten group were no longer eligible at 24 weeks compared with 15 (52%) from the placebo group (P = 0.002). CONCLUSIONS: Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).

Effects of COVID-19 on Irish general practice activity from 2019 to 2021: a retrospective analysis of 500,000 consultations using electronic medical record data.

BACKGROUND: General practice (GP) is crucial to primary care delivery in the Republic of Ireland and is almost fully computerised. General practice teams were the first point of contact for much COVID-19-related care and there were concerns routine healthcare activities could be disrupted due to COVID-19 and related restrictions. AIMS: The study aimed to assess effects of the pandemic on GP activity through analysis of electronic medical record data from general practice clinics in the Irish Midwest. METHODS: A retrospective, descriptive study of electronic medical record data relating to patient record updates, appointments and medications prescribed across 10 GP clinics over the period 2019-2021 inclusive. RESULTS: Data relating to 1.18 million record transactions for 32 k patients were analysed. Over 500 k appointments were examined, and demographic trends presented. Overall appointment and prescribing activity increased over the study period, while a dip was observed immediately after the pandemic's arrival in March 2020. Delivery of non-childhood immunisations increased sixfold as a result of COVID-19, childhood immunisation activity was maintained, while cervical smears decreased in 2020 as the screening programme was halted. A quarter of consultations in 2020 and 2021 were teleconsultations, and these were more commonplace for younger patients. CONCLUSIONS: General practice responded robustly to the pandemic by taking on additional activities while maintaining routine services where possible. The shift to teleconsulting was a significant change in workflow. Analysing routinely collected electronic medical record data can provide valuable insights for service planning, and access to these insights would be beneficial for future pandemic responses.

Research Priorities in Pediatric Asthma Morbidity: Addressing the Impacts of Systemic Racism on Children with Asthma in the United States. An Official American Thoracic Society Workshop Report.

Background: In the United States, Black and Latino children with asthma are more likely than White children with asthma to require emergency department visits or hospitalizations because of an asthma exacerbation. Although many cite patient-level socioeconomic status and access to health care as primary drivers of disparities, there is an emerging focus on a major root cause of disparities-systemic racism. Current conceptual models of asthma disparities depict the historical and current effects of systemic racism as the foundation for unequal exposures to social determinants of health, environmental exposures, epigenetic factors, and differential healthcare access and quality. These ultimately lead to biologic changes over the life course resulting in asthma morbidity and mortality. Methods: At the 2022 American Thoracic Society International Conference, a diverse panel of experts was assembled to identify gaps and opportunities to address systemic racism in childhood asthma research. Panelists found that to examine and address the impacts of systemic racism on children with asthma, researchers and medical systems that support biomedical research will need to 1) address the current gaps in our understanding of how to conceptualize and characterize the impacts of systemic racism on child health, 2) design research studies that leverage diverse disciplines and engage the communities affected by systemic racism in identifying and designing studies to evaluate interventions that address the racialized system that contributes to disparities in asthma health outcomes, and 3) address funding mechanisms and institutional research practices that will be needed to promote antiracism practices in research and its dissemination. Results: A thorough literature review and expert opinion discussion demonstrated that there are few studies in childhood asthma that identify systemic racism as a root cause of many of the disparities seen in children with asthma. Community engagement and participation in research studies is essential to design interventions to address the racialized system in which patients and families live. Dissemination and implementation studies with an equity lens will provide the multilevel evaluations required to understand the impacts of interventions to address systemic racism and the downstream impacts. To address the impacts of systemic racism and childhood asthma, there needs to be increased training for research teams, funding for studies addressing research that evaluates the impacts of racism, funding for diverse and multidisciplinary research teams including community members, and institutional and financial support of advocating for policy changes based on study findings. Conclusions: Innovative study design, new tools to identify the impacts of systemic racism, community engagement, and improved infrastructure and funding are all needed to support research that will address impacts of systemic racism on childhood asthma outcomes.

Development of a Novel Society of Thoracic Surgeons Aortic Surgery Mortality and Morbidity Risk Model.

BACKGROUND: The Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS-ACSD) was expanded in 2017 to include more granular detail on thoracic aortic surgeries. We describe the first validated risk model in thoracic aortic surgery from the STS-ACSD. METHODS: The study population consisted of patients undergoing non-emergent isolated ascending aortic aneurysm repair using open or clamped distal anastomoses, including those requiring aortic root or valve replacement. Model outcomes included operative mortality, 30-day major morbidity (cardiac reoperation, deep sternal wound infection, stroke, prolonged ventilation, renal failure) and a composite of both. To select the predictors, univariate associations and clinical face validity of models were examined. Models were evaluated by their ability to distinguish between patients with and without specific outcomes (discrimination) and their predictive accuracy (calibration). RESULTS: Between 2017 and 2021, 24,051 eligible patients underwent ascending aortic aneurysm surgery at 905 hospitals. Procedures included 8,913 aortic root replacements, 2,135 valve-sparing root replacements, 7,545 ascending aortic replacements with AVR, and 5,458 ascending aortic replacements. Circulatory arrest was performed in 7,316 (30.4%) of cases. Operative mortality was 1.9%, and 12.2% of patients experienced major morbidity including 2.4% incidence of stroke. The adjusted C-statistics for the model were 0.74, 0.67 and 0.67 for mortality, morbidity and the composite, respectively. Previous stroke and circulatory arrest were associated with new stroke. Genetic aortopathy was associated with less mortality. CONCLUSIONS: A new STS-ACSD risk model to predict mortality and morbidity after ascending aneurysm surgery has been developed, and predictors of better and worse outcomes have been identified.

Validating the Fluctuating Mental Status Evaluation in Neurocritically Ill Patients With Acute Stroke.

OBJECTIVES: Neurocritically ill patients are at high risk for developing delirium, which can worsen the long-term outcomes of this vulnerable population. However, existing delirium assessment tools do not account for neurologic deficits that often interfere with conventional testing and are therefore unreliable in neurocritically ill patients. We aimed to determine the accuracy and predictive validity of the Fluctuating Mental Status Evaluation (FMSE), a novel delirium screening tool developed specifically for neurocritically ill patients. DESIGN: Prospective validation study. SETTING: Neurocritical care unit at an academic medical center. PATIENTS: One hundred thirty-nine neurocritically ill stroke patients (mean age, 63.9 [sd, 15.9], median National Institutes of Health Stroke Scale score 11 [interquartile range, 2-17]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Expert raters performed daily Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-based delirium assessments, while paired FMSE assessments were performed by trained clinicians. We analyzed 717 total noncomatose days of paired assessments, of which 52% (n = 373) were rated by experts as days with delirium; 53% of subjects were delirious during one or more days. Compared with expert ratings, the overall accuracy of the FMSE was high (area under the curve [AUC], 0.85; 95% CI, 0.82-0.87). FMSE scores greater than or equal to 1 had 86% sensitivity and 74% specificity on a per-assessment basis, while scores greater than or equal to 2 had 70% sensitivity and 88% specificity. Accuracy remained high in patients with aphasia (FMSE ≥ 1: 82% sensitivity, 64% specificity; FMSE ≥ 2: 64% sensitivity, 84% specificity) and those with decreased arousal (FMSE ≥ 1: 87% sensitivity, 77% specificity; FMSE ≥ 2: 71% sensitivity, 90% specificity). Positive FMSE assessments also had excellent accuracy when predicting functional outcomes at discharge (AUC, 0.86 [95% CI, 0.79-0.93]) and 3 months (AUC, 0.85 [95% CI, 0.78-0.92]). CONCLUSIONS: In this validation study, we found that the FMSE was an accurate delirium screening tool in neurocritically ill stroke patients. FMSE scores greater than or equal to 1 indicate "possible" delirium and should be used when prioritizing sensitivity, whereas scores greater than or equal to 2 indicate "probable" delirium and should be used when prioritizing specificity.

Minimally Invasive CABG Is The Future: Pro.

Coronary artery bypass grafting (CABG) remains one of the most commonly performed operations worldwide. However, most CABG operations performed today are as invasive -apart from saphenous vein harvesting- as they were 50 years ago. While heart valve operations have become less invasive, CABG faces formidable challenges in doing so. Valve surgery requires a single surgical exposure to the valve intervened on, but less invasive CABG necessitates multiple surgical exposures to harvest internal thoracic artery conduits, source their inflow plus that of other grafts, and expose each coronary target to be grafted -including anterior, lateral, posterior, and inferior vessels. In this article, we rationalize why we believe that conventional CABG remains unduly invasive, associated with morbidity and prolonged recovery, and why less invasive CABG in its many forms, which we describe, represents a safe, practical, diffusible, and less invasive alternative to sternotomy CABG. Centers of excellence in coronary artery surgery should dedicate resources and expertise to developing high-quality, safe, durable, and advanced forms of lesser invasive CABG.

Single Institutional Cross-Sectional Phone Survey Study: Evaluation of Causes for Loss to Follow-up After Spinal Cord Stimulator Implantation.

BACKGROUND: Spinal cord stimulation (SCS) is often an option of last resort for patients with post-laminectomy syndrome or an alternative option for patients with complex regional pain syndrome, chronic nonsurgical low back pain, or painful diabetic peripheral neuropathy when conservative management has failed. Although SCS is a helpful option, it is not without complications that can frequently lead to explantation of the SCS device and dissatisfaction with the treatment. Furthermore, as with any technology, SCS has potential issues that may lead to patient frustration and ultimately result in patient noncompliance and lack of follow-up visits. OBJECTIVES: The goals of this study are to explore the magnitude of and reasons for patient loss to follow-up after SCS device implantation. STUDY DESIGN: A cross-sectional phone survey. SETTING: A tertiary-care academic hospital. METHODS: A cross-sectional phone survey was performed on 49 patients who were deemed lost to follow-up when they did not return to the clinic one month after being implanted with permanent SCS devices at Beth Israel Deaconess Medical Center. Patients were administered an institutional review board-approved questionnaire exploring their reasons for not returning to the clinic. RESULTS: Over a 5-year period, 257 patients underwent full implantation of an SCS device. Of the 49 patients lost to follow-up, 24 were able to be contacted, and they completed the questionnaire. Twenty of the patients continued to use the SCS device but were lost to follow-up for the following reasons: 58% (14/24) due to improvement of pain, 13% (3/24) due to minimal improvement in pain control, 4% (1/24) due to other urgent health conditions, and 8% (2/24) due to patient noncompliance and missing follow-up appointments (4/24). Four patients discontinued using the SCS device after an average of 1.5 years +/- one year, 12% (3/24) due to inadequate pain control and 4% (1/24) due to inability to recharge the device (1/24). Of these patients, 2 of the 4 contacted their SCS representatives for help with troubleshooting prior to discontinuation. None of the patients was explanted. LIMITATIONS: The main limitation of this study was the incompletion rate, which was 51.0% (25 out of 49 patients). CONCLUSIONS: This paper, the first cross-sectional study of loss to follow-up among patients who are implanted with SCS devices, identifies that up to 19% of patients are quickly lost to follow-up after implantation. Only half of the patients in this study could be reached, with most successfully using their device for meaningful pain control, but a substantial number of patients likely required additional device optimization for pain relief.

Two-Centre Retrospective Analysis on Selective Sensory Denervation of Shoulder Joint by Means of Cooled Radiofrequency in Chronic Shoulder Pain.

Purpose: Radiofrequency ablation has been used to treat chronic shoulder pain with mixed results. Thanks to recent anatomical studies, the precise location of articular branches of the suprascapular, lateropectoral and axillary nerves has been determined. Cooled radiofrequency is a neuroablative modality of treatment which has been demonstrated as efficient in different anatomical locations, and targeting the aforementioned nerves could result in a complete and efficient denervation of the shoulder. The aim of this study is to assess the efficacy of a fluoroscopic guided cooled radiofrequency technique for chronic shoulder pain. Patients and Methods: This is a retrospective observational study performed in two hospital in Wales and Italy (Wrexham NHS trust and Iseo Hospital). Forty-four patients were treated between December 2019 and January 2023. Follow-up was provided at 1-, 6- and 12-months post-procedure. Pain intensity was measured with a 0-10-point Numerical Rating Scale (NRS), and was assessed at rest and during movement. Disability was assessed with the Oxford Shoulder Score (OSS). All patients were treated with cooled radiofrequency under fluoroscopic guidance targeting the articular branches of the suprascapular, axillary and lateropectoral nerves. Results: In the 44 patients treated, the mean NRS significantly decreased at all follow ups, pain relief of >50% was obtained in 70.4%, 61% and 51% of the patients at 1.6 and 12 month follow-ups, respectively. Disability improved significantly, with a mean OSS at 12 months follow up of 30 ±17.5, compared to 15 ± 3 at baseline. Medication intake (non-steroidal anti-inflammatory drugs (NSAIDS) and/or opioids) significantly decreased at all follow ups. Conclusion: Cooled radiofrequency denervation can be an effective procedure to manage chronic shoulder pain, providing sustained pain relief and functional improvement in more than 50% of the patients.

Effects of 28-Day Nose-Only Inhalation of PCB52 (2,2',5,5'-Tetrachlorobiphenyl) on the Brain Transcriptome.

A semi-volatile polychlorinated biphenyl (PCB) congener, PCB52, is present in the indoor air of schools; however, the effects of inhaled PCB52 on the brain have not been investigated. This study exposed male Sprague-Dawley rats at 39 days of age and female rats at 42 days of age to PCB52 for 4hours per day over 28 consecutive days through nose-only inhalation. Neurobehavioral tests were conducted during the last 5 days of exposure. The total estimated PCB52 exposures after 28 days were 1080±20µg/kg BW for male rats and 1140±10µg/kg BW for female rats. PCB52 and its metabolites were detected by gas chromatography-tandem mass spectrometry in the brain, lung, and serum, with the lung showing the highest concentrations. PCB52 levels were higher in the brains of females than males. Males showed increased exploratory behavior compared to controls, whereas females exhibited decreased exploratory behavior compared to controls in the same tests. PCB52 exposure did not impact locomotor activity or working memory. Gene expression and pathway analysis in the striatum and cerebellum suggest that PCB52 inhalation causes mitochondrial dysfunction. No significant differences were observed by immunohistochemical evaluation in the density and percent area of total cells, astrocytes, or microglia in the striatum and cerebellar cortex. Our results indicate multilevel effects of inhaled PCB52 on the rat brain, from gene expression to behavioral effects.

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors.

INTRODUCTION: Renal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). METHODS: We identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. RESULTS: At 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). CONCLUSIONS: Volume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

Heterozygous loss-of-function variants in SPTAN1 cause a novel early childhood onset distal myopathy with chronic neurogenic features.

Background: Neurogenetic disorders caused by pathogenic variants in four genes encoding non-erythrocytic spectrins ( SPTAN1, SPTBN1, SPTBN2, SPTBN4) range from peripheral and central nervous system involvement to complex syndromic presentations. Heterozygous pathogenic variants in SPTAN1 are exemplary for this diversity with phenotypes spanning almost the entire spectrum. Methods: Through international collaboration we identified 14 families with genetically unsolved distal weakness and unreported heterozygous SPTAN1 loss-of-function variants including frameshift, nonsense and splice-acceptor variants. Clinical data, electrophysiology, muscle CT or MRI and muscle biopsy findings were collected and standardized. SPTAN1 protein, mRNA expression analysis and cDNA sequencing was performed on muscle tissue from two patients. Results: All 20 patients presented with early childhood onset distal weakness. The severity varied both within families and between different families. Foot abnormalities ranged from hammer toes and pes cavus to distal arthrogryposis. Electrophysiology showed mixed myogenic and neurogenic features. Muscle MRI or CT in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes with mild dystrophic and chronic neurogenic changes in 7 patients. Finally, we provide proof for nonsense mediated decay in tissues derived from two patients. Conclusions: We provide evidence for the association of SPTAN1 loss-of-function variants with childhood onset distal myopathy in 14 families. This finding extends the phenotypic spectrum of SPTAN1 loss-of-function variants ranging from intellectual disability to distal weakness with a predominant myogenic cause. KEY MESSAGES: SPTAN1 loss-of-function variants, including frameshift, nonsense and splice site variants cause a novel childhood onset distal weakness syndrome with primarily skeletal muscle involvement. Hereditary motor neuropathies and distal myopathic disorders present a well-known diagnostic challenge as they demonstrate substantial clinical and genetic overlap. The emergence of SPTAN1 loss-of-function variants serves as a noteworthy example, highlighting a growing convergence in the spectrum of genotypes linked to both hereditary motor neuropathies and distal myopathies.

Machine learning in the prevention of heart failure.

Heart failure (HF) is a global pandemic with a growing prevalence and is a growing burden on the healthcare system. Machine learning (ML) has the potential to revolutionize medicine and can be applied in many different forms to aid in the prevention of symptomatic HF (stage C). HF prevention currently has several challenges, specifically in the detection of pre-HF (stage B). HF events are missed in contemporary models, limited therapeutic options are proven to prevent HF, and the prevention of HF with preserved ejection is particularly lacking. ML has the potential to overcome these challenges through existing and future models. ML has limitations, but the many benefits of ML outweigh these limitations and risks in most scenarios. ML can be applied in HF prevention through various strategies such as refinement of incident HF risk prediction models, capturing diagnostic signs from available tests such as electrocardiograms, chest x-rays, or echocardiograms to identify structural/functional cardiac abnormalities suggestive of pre-HF (stage B HF), and interpretation of biomarkers and epigenetic data. Altogether, ML is able to expand the screening of individuals at risk for HF (stage A HF), identify populations with pre-HF (stage B HF), predict the risk of incident stage C HF events, and offer the ability to intervene early to prevent progression to or decline in stage C HF. In this narrative review, we discuss the methods by which ML is utilized in HF prevention, the benefits and pitfalls of ML in HF risk prediction, and the future directions.