Interaction of physical activity and low-level air pollution on cardiovascular disease: a prospective cohort study in UK Biobank.

To investigate the associations of physical activity (PA), low-level air pollution, and interaction on cardiovascular diseases (CVD) incidence based on the UK Biobank. PA was measured by the International Physical Activity Questionnaire and five air pollutants were estimated using Land Use Regression. All association estimates were based on Cox regression. Dose-response relationship was explored by restricted cubic spline, while multiplicative and additive interaction were examined by Pinteraction and relative excess risk due to interaction (RERI). As deviating proportional hazards assumption, we analyzed data as follow-up < 4 years and ≥ 4 years, separately. PA with 1000-4000 Metabolic Equivalent Task (MET) min/week showed the strongest protective impact on CVD incidence, while only low-level nitrogen dioxides (NO2) showed negative impact among five air pollutants and was considered for further analysis. Multiplicative interaction between PA and NO2 was observed during ≥ 4 years follow-up (Pinteraction = 0.049) while not during < 4 years (Pinteraction = 0.290). Positive additive interactions were found for high PA and low NO2 (< 20 µg/m3) group (RERI: 0.07, 95% confidence intervals: 0.02-0.11) during < 4 years, and for moderate PA with NO2 at 40- µg/m3 (0.07, 0.02-0.13) and < 20 µg/m3 (0.07, 0.02-0.12), while high PA showed similar results with NO2 at 40-, 20- and < 20 µg/m3 during ≥ 4 years. PA about 1000-4000 METs min/week showed the lowest CVD risk. Possibility of interaction with PA and NO2 is more likely to present with the increase in follow-up duration. We call for the optimal thresholds of PA, and exploring interaction thoroughly by considering types of PA.

Comparison between the for-profit human milk industry and nonprofit human milk banking: Time for regulation?

Human milk (HM) is a highly evolutionary selected, complex biofluid, which provides tailored nutrition, immune system support and developmental cues that are unique to each maternal-infant dyad. In the absence of maternal milk, the World Health Organisation recommends vulnerable infants should be fed with screened donor HM (DHM) from a HM bank (HMB) ideally embedded in local or regional lactation support services. However, demand for HM products has arisen from an increasing awareness of the developmental and health impacts of the early introduction of formula and a lack of prioritisation into government-funded and nonprofit milk banking and innovation. This survey of global nonprofit milk bank leaders aimed to outline the trends, commonalities and differences between nonprofit and for-profit HM banking, examine strategies regarding the marketing and placement of products to hospital and public customers and outline the key social, ethical and human rights concerns. The survey captured information from 59 milk bank leaders in 30 countries from every populated continent. In total, five companies are currently trading HM products with several early-stage private milk companies (PMCs). Products tended to be more expensive from PMC than HMB, milk providers were financially remunerated and lactation support for milk providers and recipients was not a core function of PMCs. Current regulatory frameworks for HM vary widely, with the majority of countries lacking any framework, and most others placing HM within food legislation, which does not include the support and care of milk donors and recipient prioritisation. Regulation as a Medical Product of Human Origin was only in place to prevent the sale of HM in four countries; export and import of HM was banned in two countries. This paper discusses the safety and ethical concerns raised by the commodification of HM and the opportunities policymakers have globally and country-level to limit the potential for exploitation and the undermining of breastfeeding.

Association between Sleep Factors and Parkinson's Disease: A Prospective Study Based on 409,923 UK Biobank Participants.

INTRODUCTION: Limited evidence indicates an association between sleep factors and the risk of Parkinson's disease (PD). However, large prospective cohort studies including both sexes are needed to verify the association between daytime sleepiness, sleep duration, and PD risk. Furthermore, other sleep factors like chronotype and snoring and their impact on increased PD risk should be explored by simultaneously considering daytime sleepiness and snoring. METHODS: This study included 409,923 participants from the UK Biobank. Data on five sleep factors (chronotype, sleep duration, sleeplessness/insomnia, snoring, and daytime sleepiness) were collected using a standard self-administered questionnaire. PD occurrence was identified using linkages with primary care, hospital admission, death register, or self-report. Cox proportional hazard models were used to investigate the association between sleep factors and PD risk. Subgroup (age and sex) and sensitivity analyses were performed. RESULTS: During a median follow-up of 11.89 years, 2,158 incident PD cases were documented. The main association analysis showed that prolonged sleep duration (hazard ratio [HR]: 1.20, 95% confidence interval [CI]: 1.05, 1.37) and occasional daytime sleepiness (HR: 1.15, 95% CI: 1.04, 1.26) increased the PD risk. Compared to those who self-reported never or rarely having sleeplessness/insomnia, participants who reported usually having sleeplessness/insomnia had a decreased risk of PD (HR: 0.85, 95% CI: 0.75, 0.96). Subgroup analysis revealed that women who self-reported no snoring had a decreased PD risk (HR: 0.85; 95% CI: 0.73, 0.99). Sensitivity analyses indicated that the robustness of the results was affected by potential reverse causation and data completeness. CONCLUSION: Long sleep duration increased the PD risk, especially among men and participants ≥60 years, while snoring increased the risk of PD in women. Additional studies are needed to (i) further consider other sleep traits (e.g., rapid eye movement sleep behavior disorder and sleep apnea) that might be related to PD, (ii) objectively measure sleep-related exposure, and (iii) confirm the effects of snoring on PD risk by considering the impact of obstructive sleep apnea and investigating its underlying mechanisms.

Periodic Kinesthetic Guidance Cannot Expedite Learning Surgical Skills.

Introduction. Connecting multiple haptic devices in a master-slave fashion enables us to deliver kinesthetic (haptic) feedback from 1 person to another. This study examined whether inter-user feedback delivered from an expert to a novice would facilitate skill acquisition of the novice in learning laparoscopic surgery and expedite it compared to traditional methods. Methods. We recruited fourteen novices and divided them into 1 of 2 training groups with 6 half-hour training sessions. The task was precision cutting adopted from one of the tasks listed in Fundamentals of Laparoscopic Surgery using laparoscopic instruments. In the haptic feedback group (haptic), 8 subjects had the chance to passively feel an expert's performance before they started to practice in each training session. In the self-learning group (control), 6 subjects watched a video before practicing. Each session was video recorded, and task performance was measured by task completion time, number of grasper adjustments, and instrument crossings. Cutting accuracy, defined as the percentage of deviation of the cutting line from the predefined line, was analyzed via computer analysis. Results. Results show no significant difference among performance measures between the 2 groups. Participants performed similarly when practicing alone or with periodic haptic feedback. Discussion. Further research will be needed for improving our way of integrating between-person haptic feedback with skills training protocol.

Fertility considerations in transgender patients.

PURPOSE OF REVIEW: An update on the latest advances in fertility preservation for transgender women, with an emphasis on the attitudes, access, and techniques. RECENT FINDINGS: With recent warming in perception toward transgendered individuals, fertility preservation services are becoming increasingly available. Although new multidisciplinary transgender clinics are appearing in North America, a 2018 report shows a referral rate for fertility preservation of only 13.5%. Despite interest in child rearing, uptake of fertility preservation is still low as patients are transitioning at increasingly younger ages. Sperm cryopreservation, ideally prior to hormonal therapy, continues to be the mainstay of fertility preservation in transwomen. It is used in conjunction with other assisted reproductive technologies such as intrauterine insemination or in-vitro fertilization with intracytoplasmic sperm injection depending on the quantity of sperm available. Recent research reporting successful autologous grafting of cryopreserved prepubertal testis leading to sperm production and offspring in macaques show great promise in the context of fertility preservation in prepubertal patients. SUMMARY: Despite the increasing accessibility of fertility preservation, referral rates and usage continue to be low, suggesting that barriers are still in place for these individuals. Clinicians must continue to counsel patients regarding the process of fertility preservation and advocate for reduction of financial and infrastructural barriers.

Tonsillectomy versus tonsillotomy for obstructive sleep-disordered breathing in children.

BACKGROUND: Obstructive sleep-disordered breathing (oSDB) is a condition encompassing breathing problems when asleep due to upper airway obstruction. In children, hypertrophy of the tonsils and/or adenoids is thought to be the commonest cause. As such, (adeno)tonsillectomy has long been the treatment of choice. A rise in partial removal of the tonsils over the last decade is due to the hypothesis that tonsillotomy is associated with lower postoperative morbidity and fewer complications. OBJECTIVES: To assess whether partial removal of the tonsils (intracapsular tonsillotomy) is as effective as total removal of the tonsils (extracapsular tonsillectomy) in relieving signs and symptoms of oSDB in children, and has lower postoperative morbidity and fewer complications. SEARCH METHODS: We searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); MEDLINE; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 22 July 2019. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of (adeno)tonsillectomy with (adeno)tonsillotomy in children aged 2 to 16 years with oSDB. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of the evidence for our pre-defined outcomes using GRADE. Our primary outcomes were disease-specific quality of life, peri-operative blood loss and the proportion of children requiring postoperative medical intervention (with or without hospitalisation). Secondary outcomes included postoperative pain, return to normal activity, recurrence of oSDB symptoms as a result of tonsil regrowth and reoperation rates. MAIN RESULTS: We included 22 studies (1984 children), with predominantly unclear or high risk of bias. Three studies used polysomnography as part of their inclusion criteria. Follow-up duration ranged from six days to six years. Although 19 studies reported on some of our outcomes, we could only pool the results from a few due both to the variety of outcomes and the measurement instruments used, and an absence of combinable data. Disease-specific quality of life Four studies (540 children; 484 (90%) analysed) reported this outcome; data could not be pooled due to the different outcome measurement instruments used. It is very uncertain whether there is any difference in disease-specific quality of life between the two surgical procedures in the short (0 to 6 months; 3 studies, 410 children), medium (7 to 13 months; 2 studies, 117 children) and long term (13 to 24 months; 1 study, 67 children) (very low-certainty evidence). Peri-operative blood loss We are uncertain whether tonsillotomy reduces peri-operative blood loss by a clinically meaningful amount (mean difference (MD) 14.06 mL, 95% CI 1.91 to 26.21 mL; 8 studies, 610 children; very low-certainty evidence). In sensitivity analysis (restricted to three studies with low risk of bias) there was no evidence of a difference between the groups. Postoperative complications requiring medical intervention (with or without hospitalisation) The risk of postoperative complications in the first week after surgery was probably lower in children who underwent tonsillotomy (4.9% versus 2.6%, risk ratio (RR) 1.75, 95% CI 1.06 to 2.91; 16 studies, 1416 children; moderate-certainty evidence). Postoperative pain Eleven studies (1017 children) reported this outcome. Pain was measured using various scales and scored by either children, parents, clinicians or study personnel. When considering postoperative pain there was little or no difference between tonsillectomy and tonsillotomy at 24 hours (10-point scale) (MD 1.09, 95% CI 0.88 to 1.29; 4 studies, 368 children); at two to three days (MD 0.93, 95% CI -0.14 to 2.00; 3 studies, 301 children); or at four to seven days (MD 1.07, 95% CI -0.40 to 2.53; 4 studies, 370 children) (all very low-certainty evidence). In sensitivity analysis (restricted to studies with low risk of bias), we found no evidence of a difference in mean pain scores between groups. Return to normal activity Tonsillotomy probably results in a faster return to normal activity. Children who underwent tonsillotomy were able to return to normal activity four days earlier (MD 3.84 days, 95% CI 0.23 to 7.44; 3 studies, 248 children; moderate-certainty evidence). Recurrence of oSDB and reoperation rates We are uncertain whether there is a difference between the groups in the short (RR 0.26, 95% CI 0.03 to 2.22; 3 studies, 186 children), medium (RR 0.35, 95% CI 0.04 to 3.23; 4 studies, 206 children) or long term (RR 0.21 95% CI 0.01 to 4.13; 1 study, 65 children) (all very low-certainty evidence). AUTHORS' CONCLUSIONS: For children with oSDB selected for tonsil surgery, tonsillotomy probably results in a faster return to normal activity (four days) and in a slight reduction in postoperative complications requiring medical intervention in the first week after surgery. This should be balanced against the clinical effectiveness of one operation over the other. However, this is not possible to determine in this review as data on the long-term effects of the two operations on oSDB symptoms, quality of life, oSDB recurrence and need for reoperation are limited and the evidence is of very low quality leading to a high degree of uncertainty about the results. More robust data from high-quality cohort studies, which may be more appropriate for detecting differences in less common events in the long term, are required to inform guidance on which tonsil surgery technique is best for children with oSDB requiring surgery.

Vortioxetine for major depressive disorder, vasomotor, and cognitive symptoms associated with the menopausal transition.

BACKGROUND: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints. METHODS: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing. RESULTS: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS ≤10) were 75% and 70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly (P = .0291 and P = .0299, respectively). CONCLUSIONS: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

GM1-gangliosidosis in American black bears: clinical, pathological, biochemical and molecular genetic characterization.

G(M1)-gangliosidosis is a rare progressive neurodegenerative disorder due to an autosomal recessively inherited deficiency of lysosomal ß-galactosidase. We have identified seven American black bears (Ursus americanus) found in the Northeast United States suffering from G(M1)-gangliosidosis. This report describes the clinical features, brain MRI, and morphologic, biochemical and molecular genetic findings in the affected bears. Brain lipids were compared with those in the brain of a G(M1)-mouse. The bears presented at ages 10-14 months in poor clinical condition, lethargic, tremulous and ataxic. They continued to decline and were humanely euthanized. The T(2)-weighted MR images of the brain of one bear disclosed white matter hyperintensity. Morphological studies of the brain from five of the bears revealed enlarged neurons with foamy cytoplasm containing granules. Axonal spheroids were present in white matter. Electron microscopic examination revealed lamellated membrane structures within neurons. Cytoplasmic vacuoles were found in the liver, kidneys and chondrocytes and foamy macrophages within the lungs. Acid ß-galactosidase activity in cultured skin fibroblasts was only 1-2% of control values. In the brain, ganglioside-bound sialic acid was increased more than 2-fold with G(M1)-ganglioside predominating. G(A1) content was also increased whereas cerebrosides and sulfatides were markedly decreased. The distribution of gangliosides was similar to that in the G(M1)-mouse brain, but the loss of myelin lipids was greater in the brain of the affected bear than in the brain of the G(M1) mouse. Isolated full-length cDNA of the black bear GLB1 gene revealed 86% homology to its human counterpart in nucleotide sequence and 82% in amino acid sequence. GLB1 cDNA from liver tissue of an affected bear contained a homozygous recessive T(1042) to C transition inducing a Tyr348 to His mutation (Y348H) within a highly conserved region of the GLB1 gene. The coincidence of several black bears with G(M1)-gangliosidosis in the same geographic area suggests increased frequency of a founder mutation in this animal population.

Value of Incremental Biopsy Cores for Microultrasound Targeted Prostate Biopsies.

OBJECTIVE: To determine the optimal number of cores needed during microultrasound-informed prostate biopsy for the detection of clinically significant prostate cancer (csPCa, defined as Gleason Grade Group ≥2). METHODS: A retrospective review of 1011 consecutive patients between September 2021 and July 2023 at our institution were identified; 536 underwent microultrasound biopsy and 475 underwent magnetic resonance imaging (MRI)/ultrasound (US) targeted biopsy. Lesions were given a Prostate Risk Identification using Microultrasound (PRI-MUS) score, with lesions PRI-MUS ≥3 targeted. MRI lesions were scored with Prostate Imaging-Reporting and Data System (PI-RADS) and lesions PI-RADS ≥3 were targeted. The primary outcome is the detection of csPCa stratified by number of cores. RESULTS: One hundred thirty-eight patients underwent targeted biopsies for microultrasound only lesions, 182 for microultrasound and MRI lesions and 426 underwent MRI/US for MRI lesions. The first targeted core detected 78.0% (46/59), 77.8% (63/81), and 78.8% (216/274) of csPCa for microultrasound, microultrasound+MRI, and MRI/US, respectively. Comparing first to third core, there was not a significant difference in overall detection of csPCa by microultrasound, though MRI/US was significantly different (28.4% vs 36.4% P = .12, 32.5% vs 41.8% P = .06, 42.5% vs 53.9% P < .001 for microultrasound, microultrasound+MRI, and MRI/US, respectively). PI-RADS 3 and PRI-MUS 3 lesions had lower first core detection rates compared to PI-RADS 5 and PRI-MUS 5 lesions (44.4% vs 85.4% P = .01, 65.2% vs 81.4% P = .14, 60% vs 83.1% P = .07 for microultrasound, microultrasound+MRI, and MRI/US, respectively). CONCLUSION: A three-core targeted biopsy per microultrasound lesion improves detection rate of csPCa and should be considered to improve diagnostic accuracy.

Micro-ultrasound for the detection of clinically significant prostate cancer in biopsy-naive men with negative MRI.

INTRODUCTION: Despite a negative magnetic resonance imaging (MRI), some patients may still harbor clinically significant prostate cancer (csPCa, Gleason grade group ≥2). High-resolution micro-ultrasound (microUS) is a novel imaging technology that could visualize csPCa that is missed by MRI. METHODS: This retrospective review included 1011 consecutive patients biopsied between September 2021 and July 2023 in Alberta, Canada. Among them were 103 biopsy-naive patients with negative MRI (Prostate Imaging Reporting & Data System [PI-RADS] ≤2) undergoing microUS-informed prostate biopsy (n=56) scored using Prostate Risk Identification Using Micro-ultrasound (PRI-MUS) or standard transrectal ultrasound prostate biopsy (n=47). The primary outcome was detection rate of csPCa stratified by biopsy technique and PRI-MUS score. RESULTS: MicroUS biopsy identified csPCa in 14/56 (25%) compared to standard biopsy in 8/47 (17%) (p=0.33). Patients with lesions PRI-MUS ≥3 had csPCa detected at a higher rate compared to patients with PRI-MUS ≤2 (42% vs. 16%, p=0.03). The csPCa detection rate was significantly different comparing patients with PSA density <0.15 and PRI-MUS ≤2 compared to patients with PSA density ≥0.15 and PRI-MUS ≥3 (14% vs. 60%, p=0.02). CONCLUSIONS: MicroUS may aid in the detection of csPCa for patients with negative MRI.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Detection of clinically significant prostate cancer by micro-ultrasound-informed systematic biopsy during MRI/micro-ultrasound fusion biopsy.

INTRODUCTION: High-resolution micro-ultrasound (microUS) is a novel imaging technique that may visualize clinically significant prostate cancer (csPCa), including those missed by magnetic resonance imaging (MRI ), in real time during prostate biopsy. METHODS: From September 2021 to January 2022, 75 consecutive biopsy-naive men were entered into an observational cohort. All men underwent an MRI /microUS fusion prostate biopsy, completed by a single surgeon using the ExactVU device. At time of biopsy, each biopsy core was given a Prostate Risk Identification using MicroUS (PRI-MUS) score. Anonymized data were entered into a RED Cap database. Cancer detection stratified by Prostate Imaging-Reporting & Data System (PI-RADS ) and PRI-MUS score, and imaging modality was captured. Our primary outcome was the detection rate of csPCa in microUS-informed systematic biopsy cores, taken outside MRI-visible lesions, during MRI /microUS fusion prostate biopsy. RESULTS: A median of three MRI-targeted and 12 microUS-informed systematic cores were taken per patient. MRI /microUS biopsy detected PCa in 84%, with csPCa detected in 52%. Of the 900 microUS-informed systematic cores, 105 cores were PRI-MUS ≥3 and 795 cores were PRI-MUS ≤2. csPCa was detected in 35% of the PRI-MUS ≥3 cores compared to 10% of the PRI-MUS ≤2 cores (p<0.0001). Detection of csPCa varied by core type: 8% of patients were diagnosed by MRI-targeted cores only, 38% were diagnosed by microUS-informed systematic cores only, and 54% were diagnosed by both. CONCLUSIONS: MicroUS-informed systematic biopsy may be a useful adjunct to MRI, with PRI-MUS ≥3 systematic cores having a 3.5-fold increased risk of csPCa compared to PRI-MUS ≤2 cores.

Development and validation of knowledge assessment scales on sarcopenia and fall for Chinese community-dwelling older adults.

AIM: This study aimed to develop and validate sarcopenia and fall knowledge assessment scales for community-dwelling older adults. METHODS: A five-phase, systematic and standardized process was used. Phase 1: item pools were constructed based on the Symptom Interpretation Model. Phase 2: the Delphi expert consultation was carried out for items selection and revision. Phase 3: a pilot survey was carried out to further select and revise the items. Phase 4: older adults were surveyed to finalize the items. Phase 5: older adults were surveyed to test the psychometric properties of the two developed scales, including construct validity, reliability and acceptability. RESULTS: Both scales comprise three dimensions (symptom, risk factor and management strategy), with 10 items for the sarcopenia knowledge assessment scale and 14 items for the fall knowledge assessment scale. They had acceptable construct validity, with all indicators meeting their specific criteria. Their reliability was acceptable, with the Cronbach's α coefficients being 0.82 for both scales, the value of spilt-half reliability being 0.86 for the sarcopenia knowledge assessment scale and 0.85 for the fall knowledge assessment scale. Their acceptability was good, with both scales having a completion rate of 94.35% and an average completion time of 5 min. DISCUSSION: Two Chinese knowledge assessment scales with acceptable validity, reliability and acceptability have been developed, which will facilitate the assessment of the knowledge on sarcopenia and fall among community-dwelling older adults, especially for large-scale surveys. Geriatr Gerontol Int 2023; 23: 430-436.

Micro-ultrasound Versus Magnetic Resonance Imaging in Prostate Cancer Active Surveillance.

Accurate assessment of tumor grade is critical for active surveillance (AS) in prostate cancer. We compared magnetic resonance imaging (MRI) and micro-ultrasound scoring (Prostate Imaging-Reporting and Data System [PI-RADS] v2.1 vs Prostate Risk Identification using Micro-ultrasound [PRI-MUS]) in 128 men on AS. The primary outcome was upgrading to Gleason grade group (GG) ≥2. There was no difference in GG ≥2 detection between the imaging techniques (PRI-MUS score ≥3: 33/34, 98%; PI-RADS score ≥3: 29/34, 85%; p = 0.22). The sensitivity, specificity, and positive and negative predictive values for GG ≥2 detection were 97%, 32%, 34%, and 97% with PRI-MUS ≥3, and 85%, 53%, 40%, and 91% with PI-RADS ≥3, respectively. Upgrading to GG ≥2 was more likely for PRI-MUS ≥3 than for PRI-MUS ≤2 scores (odds ratio 15.5, 95% confidence interval 2.0-118.5). A limitation is the lack of blinding to the MRI results. In conclusion, detection of upgrading to GG ≥2 during AS appears similar when using micro-ultrasound or MRI to inform prostate biopsy. Patient summary: We looked at a novel imaging technology, micro-ultrasound, in patients undergoing biopsy during active surveillance for prostate cancer. We found that micro-ultrasound can detect prostate cancer that may require treatment at a similar rate to that with magnetic resonance imaging (MRI) scans.

Comparison of clinical outcomes of overlapping sirolimus- versus paclitaxel-eluting stents in patients undergoing percutaneous coronary intervention.

Sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES) implantation for the treatment of single coronary lesions has proved to be effective and durable. However, the safety and efficacy of overlapping drug-eluting stents for the treatment of long lesions have not been well established. In total, 114 patients who received overlapping drug-eluting stents were identified, 55 of whom received overlapping SESs and 59 received overlapping PESs. Baseline clinical and angiographic characteristics were balanced. In-hospital complications were similar between the 2 groups. At 30-day and 6-month follow-ups, all clinical outcomes were also similar. In addition, the event-free survival rate was comparable (p = 0.71). Implantation of overlapping drug-eluting stents for the treatment of long, native coronary lesions is feasible and effective. In conclusion, in this observational study, clinical outcomes appeared similar in patients treated with overlapping SES implantation compared with those treated with overlapping PES implantation.

Impact of three or more versus a single sirolimus-eluting stent on outcomes in patients who undergo percutaneous coronary intervention.

This retrospective analysis compared clinical outcomes of patients who underwent stenting with > or =3 sirolimus-eluting stents (SESs) with those who received a single SES. SES (Cypher) implantation for single vessels is proved to be effective and durable, but knowledge regarding the safety and effectiveness of multiple stenting with SESs is currently limited. In total, 929 consecutive patients who received SESs were identified; 63 received > or =3 SESs (multi group) and 866 received 1 SES (single group). The multi group had more non-Q-wave myocardial infarctions (MIs) during the index hospitalization (p = 0.02). At 30-day follow-up, death, Q-wave MI, subacute thrombosis, and major adverse cardiac events were higher in the multi group than in the single group. At 6 months, death, Q-wave MI, target lesion revascularization, and major adverse cardiac events continued to be higher in the multi group. Using multivariate analysis, > or =3 SES implantations, American College of Cardiology/American Heart Association type C lesions, and cardiogenic shock were identified as independent predictors for 6-month major adverse cardiac events. In addition, patients in the multi group had a significantly lower survival rate than patients in the single group (p <0.0001). Patients who required > or =3 SES implantations developed increased periprocedural non-Q-wave MI and worse adverse clinical outcomes at 30 days and 6 months compared with patients who required a single SES implantation. In conclusion, when patients present with multiple coronary lesions, percutaneous coronary intervention with multiple SESs should be undertaken with great caution.

Bivalirudin versus unfractionated heparin in patients undergoing percutaneous coronary intervention after acute myocardial infarction.

BACKGROUND: Bivalirudin is replacing heparin as the anticoagulant agent of choice for elective percutaneous coronary intervention (PCI). This study aimed to assess the safety and clinical outcomes of bivalirudin versus unfractionated heparin (UFH) in patients undergoing PCI for acute myocardial infarction (AMI). METHODS: A cohort of 672 consecutive patients presenting with AMI without prior thrombolytic therapy were treated with either bivalirudin (216 patients) or UFH (456 patients). Platelet glycoprotein IIb/IIIa inhibitors were administered at the operator's discretion. The in-hospital, 30-day, and 6-month outcomes of the two groups were compared. RESULTS: Baseline clinical and angiographic characteristics were similar between the groups. In-hospital complications were similar, although there was a trend of a less major hematocrit drop in the bivalirudin group (0.9% vs. 3.1%, P=.09). All clinical outcomes were similar between the groups at 30-day and 6-month follow-ups. There was no statistical significance for acute thrombosis and subacute thrombosis between the groups, and there was no late thrombosis from either group. The event-free survival rate was similar between the groups (P=.41). CONCLUSION: The use of bivalirudin in patients undergoing PCI after AMI is safe and feasible. Bivalirudin should be considered as an alternative anticoagulant agent during PCI to treat patients presenting with AMI.

Association Between Progranulin and Gaucher Disease.

BACKGROUND: Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of ß-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. METHODS: Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy control samples. Development of GD in PGRN-deficient mice was characterized, and the therapeutic effect of rPGRN on GD analyzed. FINDINGS: Serum PGRN levels were significantly lower in GD patients (96.65±53.45ng/ml) than those in healthy controls of the general population (164.99±43.16ng/ml, p<0.0001) and of Ashkenazi Jews (150.64±33.99ng/ml, p<0.0001). Four GRN gene SNPs, including rs4792937, rs78403836, rs850713, and rs5848, and three point mutations, were identified in a full-length GRN gene sequencing in 40 GD patients. Large scale SNP genotyping in 161 GD and 142 healthy controls was conducted and the four SNP sites have significantly higher frequency in GD patients. In addition, "aged" and challenged adult PGRN null mice develop GD-like phenotypes, including typical Gaucher-like cells in lung, spleen, and bone marrow. Moreover, lysosomes in PGRN KO mice exhibit a tubular-like appearance. PGRN is required for the lysosomal appearance of GCase and its deficiency leads to GCase accumulation in the cytoplasm. More importantly, recombinant PGRN is therapeutic in various animal models of GD and human fibroblasts from GD patients. INTERPRETATION: Our data demonstrates an unknown association between PGRN and GD and identifies PGRN as an essential factor for GCase's lysosomal localization. These findings not only provide new insight into the pathogenesis of GD, but may also have implications for diagnosis and alternative targeted therapies for GD.

Optimizing dosimetry with high-dose intracoronary gamma radiation (21 Gy) for patients with diffuse in-stent restenosis.

BACKGROUND: The efficacy of intracoronary gamma radiation (IRT-gamma) in reducing recurrent in-stent restenosis (ISR) is well established using doses of 14-18 Gy. We sought to examine whether an escalation in dose to 21 Gy is safe and confers additional benefit in reducing repeat revascularization and major adverse cardiac events (MACE) in patients with diffuse ISR. METHODS: Forty-seven patients with diffuse ISR (lesion length 20-80 mm) in native coronary arteries (n=25) and saphenous vein grafts (n=22) underwent percutaneous transluminal coronary angioplasty and/or additional stents followed by IRT-gamma using the Checkmate system (Cordis) with a dose of 21 Gy. All patients were discharged with clopidogrel for 12 months and aspirin indefinitely. Six-month angiographic and 12-month clinical outcomes of these patients were compared to 120 patients treated with 18 Gy using the same system. RESULTS: At baseline, patients in the 21-Gy group had more multivessel, vein graft disease and history of prior myocardial infarctions and coronary artery bypass grafts (P<.001). The use of debulking devices and stents was less in this group (P<.001). Procedural and in-hospital complications were similar. Follow-up at 6 months revealed nonsignificant but lower late loss (in-stent, 0.33+/-0.7 mm; in-lesion, 0.41+/-0.6 mm) in the 21-Gy group compared to the 18-Gy group; follow-up at 12 months revealed a trend toward less overall myocardial infarction, although repeat revascularization and MACE rates were similar. CONCLUSIONS: IRT-gamma therapy for diffuse ISR lesions with a 21-Gy dose is clinically safe and feasible with marked reduction in late loss but does not confer additional benefit with regard to repeat revascularization and MACE when compared to a dose of 18 Gy.