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Background & aims A potential protection against COVID-19 by a high-quality dietary pattern is to be expected given the biological plausibility supporting the beneficial effects of an adequate dietary intake on the immune system. However, knowledge on the relationship between long-term maintained healthy dietary patterns, such as the Mediterranean diet, and the risk of SARS-CoV-2 infection is still sparse. We longitudinally assessed this association in a well-known Mediterranean cohort. Methods We assessed 9,677 participants from the SUN Project, a prospective cohort of middle-aged university graduates in Spain. We inquired about a positive result in a COVID-19 diagnostic test during the months of February to December 2020. After excluding health professionals (HP), 5,194 participants were included in the statistical analyses (mean age: 52.6, SD: 12.4; 55.2% women). Food habits were assessed at baseline using a previously validated semiquantitative 136-item food frequency questionnaire. Adherence to the Mediterranean diet (cumulative average of 2 repeated measurements 10 years apart) was assessed using the 0-to-9 Mediterranean Diet Score (MDS). We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident COVID-19 according to the MDS. Results Among 5,194 non-HP participants, 122 reported to have received a positive COVID-19 diagnostic test. Participants with intermediate adherence to the Mediterranean diet (3 < MDS ≤ 6) had a significantly lower odds of developing COVID-19 (multivariable-adjusted OR = 0.50, 95% CI: 0.34–0.73), and those with the highest adherence (MDS > 6) exhibited the lowest risk (multivariable-adjusted OR = 0.36, 95% CI: 0.16–0.84, p for trend

Docosahexaenoic acid (DHA) shows anti-inflammatory/proresolution effects in the brain. Higher red blood cell (RBC) DHA in humans is associated with improved cognitive performance and a lower risk for suicide. Here, we hypothesized that binding to the 18 kDa translocator protein (TSPO), a proxy for microglia levels, will be higher in individuals with low DHA relative to high DHA levels. We also postulated that higher TSPO would predict poor cognitive performance and impaired stress resilience.RBC DHA screening was performed in 320 healthy males. [sup11/supC]PBR28 positron emission tomography was used to measure binding to TSPO in 38 and 32 males in the lowest and highest RBC DHA quartiles. Volumes of distribution expressed relative to total plasma ligand concentration (VsubT/sub) was derived using an arterial input function-based kinetic analysis in 14 brain regions.[sup11/supC]PBR28 VsubT/subwas significantly lower (by 12% and 20% in C/T and C/C rs6971 genotypes) in males with low RBC DHA than in males with high RBC DHA. Regional VsubT/subwas correlated positively and negatively with RBC DHA and serum triglycerides, respectively. No relationships between VsubT/suband cognitive performance or stress resilience measures were present.Contrary to our hypothesis, we found lower TSPO binding in low-DHA than in high-DHA subjects. It is unclear as to whether low TSPO binding reflects differences in microglia levels and/or triglyceride metabolism in this study. Future studies with specific targets are necessary to confirm the effect of DHA on microglia. These results underscore the need to consider lipid parameters as a factor when interpreting TSPO positron emission tomography clinical findings.

Purpose: To examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults. Methods: This prospective cohort study involved 768 community-dwelling Spanish older adults (78.8 § 4.9 years, mean § SD; 53.9% females) from the Toledo Study for Healthy Aging (2012 2017). The number of steps per day and step cadence (steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline. Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality. Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality. Results: Included participants walked 5835 § 3445 steps/day (mean § SD) with an intensity of 7.3 § 4.1 steps/min. After adjusting for age, sex, body mass index (BMI), education, income, marital status and comorbidities, higher step count (hazard ratio (HR) = 0.95, 95% confidence inter vals (95%CI: 0.90 1.00, and HR = 0.87, 95%CI: 0.81 0.95 per additional 1000 steps) and higher step intensity (HR = 0.95, 95%CI: 0.91 0.99, and HR = 0.89, 95%CI: 0.84 0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk, respectively. Compared to the group having low step volume and intensity, individuals in the group having high step volume and intensity had a lower risk of hospitalization (HR = 0.72, 95%CI: 0.52 0.98) and all-cause mortality (HR = 0.60, 95%CI: 0.37 0.98). Conclusion: Among older adults, both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk. Increasing step volume and intensity may benefit older people.

AIM Reports have shown that physical activity is inversely associated with heart failure risk, but evidence in Asian populations is lacking. We sought to examine the impacts of walking and sports participation on heart failure mortality among a Japanese population. METHODS We involved 36,223 Japanese men and 50,615 women (aged 40-79 years) who completed a self-administered questionnaire between 1988 and 1990. We divided participants into four categories of walking (＜0.5, 0.5, 0.6-1.0, and ≥ 1 h/day) and sports participation (＜1, 1-2, 3-4, and ≥ 5 h/week) and examined associations with activity and heart failure mortality through 2009. RESULTS We found inverse associations between physical activity and heart failure mortality. The multivariable hazard ratios (95% confidence intervals) for the highest category of walking time compared with the second-lowest category were 0.76 (0.59-0.99) in men and 0.78 (0.61-0.99) in women, while the ratios for the highest category of sports participation time compared with the second-lowest category were 0.62 (0.41-0.93) in men and 1.09 (0.73-1.65) in women. The lower hazard ratios in the highest categories of walking and sports participation time in men became no longer statistically significant after excluding heart failure deaths for the first 5, 10, and 15 years for walking time and 10 and 15 years for sports participation. However, in women, the low hazard ratios for the highest category ≥ 1.0 h/day of walking time did not change materially. CONCLUSIONS Physical activity was associated with a lower risk of mortality from heart failure in this Japanese community-based population. The attenuated and nonsignificant association of walking and sports participation with the risk in men after exclusion of first 5-15 years heart failure death was probably due to changes in physical activity and death certificate diagnosis during the follow-up and reverse causation. However, the persistent inverse association between walking and the risk in women suggests a beneficial preventive effect on heart failure.

Background In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association of anti-hypertensive drug initiation and outcomes in patients with HFrEF. Methods In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in matched cohort. Results Matched patients (n=1374) had a mean age of 74 years, 41% were women, 17% were African American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83–1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80–1.07). Similar associations were observed during 30 days and 12 months of follow-up. Conclusions Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

Objectives : Frailty has been correlated with poor outcomes after major surgery across multiple specialties, but has not been studied in patients undergoing open or endovascular repair of suprarenal and thoracoabdominal aortic aneurysms. Fenestrated endovascular aneurysm repair (FEVAR) has emerged as a lower risk alternative to open surgical repair (OSR) for patients with complex aortic aneurysms involving the visceral artery branches. The objective of the current study was to examine the relationship between frailty and peri-operative outcomes for FEVAR and OSR in patients with suprarenal and thoracoabdominal aortic aneurysms. Methods : The American College of Surgeons—National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent FEVAR or OSR for the years 2011 through 2017. Frailty was quantified using a modified 5-factor frailty index (mFI-5) that was previously validated for surgical patients. Frailty was correlated with the primary endpoint of 30-day mortality. Logistic regression was used to identify predictors of 30-day mortality. Results : A total of 675 FEVAR and 1,779 OSR operations were included in the analysis. The 30-day mortality rate was 3.0% for FEVAR and 7.1% for OSR (P=0.002). Increasing frailty was significantly associated with higher 30-day mortality for both FEVAR (P=0.018) and OSR (P=0.0003). Independent predictors of 30-day mortality were frailty score (Odds Ratio [OR] 1.22 [per 0.1-unit increase]; P = .0005), type of repair (OSR vs. FEVAR, OR 2.46; P = .0001), age (OR 1.03; P = .0025), female sex (OR 1.61; P = .007), Hispanic ethnicity (OR 2.68; P = .021), American Society of Anesthesiology [ASA] class (OR 1.57; P = .035), preoperative dialysis (OR 3.45; P = .032), and history of bleeding disorder (OR 2.60; P Conclusions : Frailty, as measured using a mFI-5 score, is an independent predictor of 30-day mortality, overall complications, and length of stay after FEVAR or OSR. Frailty should be used to identify patients at high risk of adverse postoperative outcomes to determine if this risk is modifiable or whether nonoperative is the most appropriate option. FEVAR may offer improved 30-day outcomes, compared to OSR, for the frailest patients.

Background Home Based Cardiac Rehabilitation (HBCR) has been considered a reasonable alternative to Center-based Cardiac Rehabilitation (CBCR) in patients with established cardiovascular disease, especially in the midst of COVID-19 pandemic. However, the long-term cardiovascular outcomes of patients referred to HBCR remains unknown. Objectives To compare outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR). Methods We performed a retrospective study of 269 patients referred to HBCR at Providence Veterans Affairs Medical Center (PVAMC). From November 2017 to March 2020, 427 patients were eligible and referred for Cardiac Rehabilitation (CR) at PVAMC. Of total patients, 158 patients were referred to CBCR and 269 patients to HBCR based on patient and/or clinician preference. The analysis of outcomes was focused on HBCR patients. We compared outcomes of patients who were referred and attended HBCR vs patients referred but did not attend HBCR (Non-HBCR) from 3 to 12 months of the referral date. HBCR consisted of face-to-face entry exam with exercise prescription, weekly phone calls for education and exercise monitoring, with adjustments where applicable, for 12-weeks and an exit exam. Primary outcome was composite of all-cause mortality and hospitalizations. Secondary outcomes were all-cause hospitalization, all-cause mortality and cardiovascular hospitalizations, separately. We used cox proportional methods to calculate hazard ratios (HR) and 95% CI. We adjusted for imbalanced characteristics at baseline: smoking, left ventricular ejection fraction and CABG status. Results A total of 269 patients (mean age: 72, 98% Male) were referred to HBCR, however, only 157 (58%) patients attended HBCR. The primary outcome occurred in 30 patients (19.1%) in the HBCR group and 30 patients (30%) in the Non-HBCR group (adjusted HR=0.56, CI 0.33-0.95, P=.03). All-cause mortality occurred in 6.4% of patients in the HBCR group and 13% patients in the Non-HBCR group 3 to 12 months after HBCR referral (adjusted HR=0.43, CI 0.18-1.0, P= .05). There was no difference in cardiovascular hospitalizations (HBCR: 5.7% vs Non-HBCR: 10%, adjusted HR 0.57, CI 0.22-1.4, P= .23) or all cause hospitalizations at 3 to 12 months between the groups (HBCR: 12.7% vs Non-HBCR: 21%, adjusted HR 0.53, CI 0.28-1.01, P= .05). Conclusion Completion of HBCR among referred patients was associated with a lower risk of the combined all-cause mortality and all-cause hospitalizations up to 12 months. Based on the outcomes, HBCR is a reasonable option that can improve access to CR for patients who are not candidates of or cannot attend CBCR. Randomized-controlled studies are needed to confirm these findings.

Purpose In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR. Methods We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires. Results Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank P Conclusion Boron may be an overlooked target to improve long-term survival among KTR and potentially other patients, likely through pathways other than inflammation or the methionine-homocysteine cycle that were previously suggested. Interventional trials are warranted to confirm the potential of dietary boron supplementation in KTR and other patient populations.

BACKGROUND: It is currently unknown if within high-quality dietary intake there exist distinct dietary patterns associated with health benefits that are identifiable with multidimensional dietary pattern analyses. The purpose of this study was to identify specific dietary patterns and groups therein and their associations with all-cause, CVD, and cancer mortality. METHODS: We conducted sex-specific k-means cluster analyses within Healthy Eating Index 2015 (HEI-2015) quintile 5 in 3 US cohorts [NIH-American Association of Retired Persons Diet and Health Study (AARP), the Multiethnic Cohort (MEC), Women's Health Initiative Observational Study (WHI OS)], clusters ranging from n = 1190 to n = 12,007. Characterizations incorporated HEI-2015 overall and component-specific percentage adherence goals, using untruncated and truncated radar graphs and shape analyses. Using cohort- and sex-specific Cox proportional hazards models, associations of quintile 5 clusters with all-cause, cardiovascular disease (CVD), and cancer mortality were evaluated relative to quintile 1. RESULTS: In each cohort sex-specific sample, 3 identified clusters included 16%–62% of participants, providing evidence for variation within high-quality dietary intake. Clusters revealed commonalities in total fruits and whole fruits intakes that exceeded goals and high sodium intake. Dairy and whole grain intakes oftentimes fell below goal. Some clusters were in addition characterized by total vegetables, greens & beans, and seafood & plant protein intakes exceeding goals. All high-quality dietary patterns were associated with a multivariable-adjusted significant 15%–26% lower risk of all-cause death than diet intake in quintile 1 (except for cluster 2 in WHI OS), and with a 16%–25% lower risk of CVD mortality in the AARP and MEC cohorts. Cancer mortality results were inconsistent. CONCLUSIONS: Multiple ways to achieve a high-quality diet were identified and significant associations with lower all-cause and CVD mortality were seen in some cohorts.

Randomized studies have validated laparoscopic proctectomy for the treatment of rectal cancer as noninferior to an open proctectomy, but most of those studies have included sphincter-preserving resections along with abdominoperineal resection.This study aimed to compare perioperative and long-term oncological outcomes between minimally invasive and open abdominoperineal resection.This study is a retrospective analysis of a prospectively maintained database.The study was conducted in a single specialized colorectal surgery department.All patients who underwent abdominoperineal resection for primary rectal cancer between 2000 and 2016 were included.The primary outcomes measured were the perioperative and long-term oncological outcomes.We included 452 patients, 372 in the open group and 80 in the minimally invasive group, with a median follow-up time of 74 months. There were significant differences between the groups in terms of neoadjuvant radiation treatment (67.5% of the open versus 81.3% of the minimally invasive group, p = 0.01), operative time (mean of 200 minutes versus 287 minutes, p0.0001), and mean length of stay (9.5 days versus 6.6 days, p0.0001). Overall complication rates were similar between the groups (34.5% versus 27.5%, p = 0.177). There were no significant differences in the mean number of lymph nodes harvested (21.7 versus 22.2 nodes, p = 0.7), circumferential radial margins (1.48 cm versus 1.37 cm, p = 0.4), or in the rate of involved radial margins (10.8% versus 6.3%, p = 0.37). Five-year overall survival was 70% in the open group versus 80% in the minimally invasive group (p = 0.344), whereas the 5-year disease-free survival rate in the open group was 63.2% versus 77.6% in the minimally invasive group (p = 0.09).This study was limited because it describes a single referral institution experience.Although both approaches have similar perioperative outcomes, the minimally invasive approach benefits the patients with a shorter length of stay and a lower risk for surgical wound infections. Both approaches yield similar oncological technical quality in terms of the lymph nodes harvested and margins status, and they have comparable long-term oncological outcomes. See Video Abstract at http://links.lww.com/DCR/B754.RESULTADOS A LARGO PLAZO DE LA RESECCIÓN ABDOMINOPERINEAL MÍNIMAMENTE INVASIVA VERSUS ABIERTA PARA EL CÁNCER DE RECTO: EXPERIENCIA DE UN SOLO CENTRO ESPECIALIZADOANTECEDENTES:Estudios aleatorizados han validado la proctectomía laparoscópica para el tratamiento del cáncer de recto igual a la proctectomía abierta, pero la mayoría de esos estudios han incluido resecciones con preservación del esfínter junto con resección abdominoperineal.OBJETIVO:Comparar los resultados oncológicos perioperatorios y a largo plazo entre la resección abdominoperineal abierta y mínimamente invasiva.DISEÑO:Análisis retrospectivo de una base de datos mantenida de forma prospectiva.ENTORNO CLINICO:Servicio único especializado en cirugía colorrectal.PACIENTES:Todos los pacientes que se sometieron a resección abdominoperineal por cáncer de recto primario entre 2000 y 2016.PRINCIPALES MEDIDAS DE VALORACION:Resultados oncológicos perioperatorios y a largo plazo.RESULTADOS:Se incluyeron 452 pacientes, 372 en el grupo abierto y 80 en el grupo mínimamente invasivo, con una mediana de seguimiento de 74 meses. Hubo diferencias significativas entre los grupos en términos de tratamiento con radiación neoadyuvante (67,5% del grupo abierto versus 81,3% del grupo mínimamente invasivo, p = 0,01), tiempo operatorio (media de 200 minutos versus 287 minutos, p0,0001) y la duración media de la estancia (9,5 días frente a 6,6 días, p0,0001). Las tasas generales de complicaciones fueron similares entre los grupos (34,5% versus 27,5%, p = 0,177). No hubo diferencias significativas en el número medio de ganglios linfáticos extraídos (21,7 versus 22,2 ganglios, p = 0,7), márgenes radiales circunferenciales (1,48 cm y 1,37 cm, p = 0,4), ni en la tasa de márgenes radiales afectados (10,8 cm). % versus 6,3%, p = 0,37). La supervivencia general a 5 años fue del 70% en el grupo abierto frente al 80% en el grupo mínimamente invasivo (p = 0,344), mientras que la tasa de supervivencia libre de enfermedad a 5 años en el grupo abierto fue del 63,2% frente al 77,6% en el grupo mínimamente invasivo (p = 0,09).LIMITACIONES:Experiencia en una institución de referencia única.CONCLUSIONES:Si bien ambos tienen resultados perioperatorios similares, el enfoque mínimamente invasivo, beneficia a los pacientes con estadía más corta y menor riesgo de infecciones de la herida quirúrgica. Ambos enfoques, producen una calidad técnica oncológica similar en términos de ganglios linfáticos extraídos y estado de los márgenes, y tienen resultados oncológicos comparables a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B754. (Traducción - Dr. Fidel Ruiz Healy).

Colorectal cancer (CRC) screening has been demonstrated to reduce CRC incidence and mortality. However, besides such benefits, CRC screening is also associated with potential harmful effects. In an ideal world, screening would only be directed to the small proportion of the population that might potentially benefit. Risk-based screening can be seen as a first step towards this ideal world, by redistributing screening resources from low-risk to high-risk individuals. In theory, this should result in scarce resources being used in individuals who benefit most, while intensity of screening is reduced in individuals who benefit less, hence improving the benefit-harm ratio among all invitees. Available strategies that have been proposed for risk-based CRC screening include using information on age, sex, prior screening history, lifestyle and/or genetic information. Implementation of risk-based screening requires careful consideration of reliable risk prediction models, participation with screening and informed decision-making. While it is important to recognise the limitations of current approaches, available evidence suggests that it might be feasible to start planning the introduction of tailored strategies within screening programmes. Implementing risk-based screening based on age, sex and prior screening history alone would already represent a substantial improvement over current uniform screening approaches. We propose that it is time that screening programmes start there and continue striving towards more comprehensive approaches embedding primary prevention as an effective approach to lower risk for everyone.

Background Nutrients that support the desired growth and development of the fetus (i.e., micronutrients like folate, iron, and zinc) have been associated with birth outcomes, such as gestational age at delivery and birth weight. Objective We characterized the maternal dietary patterns that explain the maximum variation in folate, iron, and zinc intakes in pregnant Korean women using reduced-rank regression (RRR) and investigated the association of these patterns with small-for-gestational-age (SGA) risk. Methods A total of 1,158 pregnant Korean women at 12-28 weeks gestation and their newborns were recruited for the Mothers and Children's Environmental Health (MOCEH) study between 2006 and 2010. A semiquantitative food frequency questionnaire was collected from the women, and RRR was used to derive their dietary patterns. Log-transformed maternal intakes of folate, iron, and zinc were selected as the intermediate response variables to extract dietary patterns. Infant birth outcome measurements were obtained from hospital records. Associations were assessed by logistic regression with adjustment for confounding factors. Results Three dietary patterns were identified. Pattern 1, characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts, was associated with a lower risk of SGA in the highest quartile compared to the lowest quartile (odds ratio: 0.36; 95% confidence interval: 0.14, 0.94). Especially, maternal dietary pattern 1 was negatively related to high-sensitivity C-reactive protein in the blood and malondialdehyde levels in the urine. No association was observed for other dietary patterns with SGA. Conclusions Among pregnant Korean women, adherence to a dietary pattern characterized by high intakes of grains, green/yellow and light-colored vegetables, kimchi, legumes, fruits, meat, eggs, fish, seaweeds, tofu/soymilk, yogurt, and nuts is associated with a lower risk of delivering SGA infants.

Background In Pakistan, the prevalence of stunting among children under-five years has remained above WHO critical thresholds (≥30%) over the last two decades. Objective We hypothesized that an unconditional cash transfer (UCT) combined with lipid-based nutrient supplement (LNS) and/or social and behavior change communication (SBCC) will prevent stunting among children 6-23 months of age. Design This was a four-arm, community-based cluster randomized controlled trial conducted in the district of Rahim Yar Khan, Pakistan. A total of 1729 children (UCT n = 434); (UCT+SBCC n = 433); (UCT+LNS n = 430) and (UCT+LNS+SBCC n = 432) were enrolled at 6 months of age and measured monthly for 18 months until the age of 24 months. Results At 24 months of age, children who received UCT+LNS (rate ratio [RR], 0.85 [95% CI 0.74, 0.97]; P = 0.015); and UCT+LNS+SBCC (RR, 0.86 [95% CI 0.77, 0.96]; P = 0.007) had significantly lower risk of being stunted as compared to the UCT arm. No significant difference was noted among children who received UCT+SBCC (RR, 1.03 [95% CI 0.91, 1.16]; P = 0.675) in the risk of being stunted as compared to the UCT arm. The pooled prevalence of stunting among children 6-23 months was 41.7%, 44.8%, 38.5% and 39.3% in UCT, UCT+SBCC, UCT+LNS and UCT+LNS+SBCC, respectively. In pairwise comparisons, a significant impact on stunting among children in UCT+LNS (P = 0.029) and UCT+LNS+SBCC (P = Conclusions UCT combined with LNS and UCT+LNS+SBCC were effective in reducing the prevalence of stunting among children aged 6-23 months in marginalized populations. UCT+SBCC was not effective in reducing the child stunting prevalence.Clinical trial registration number: ClinicalTrials.gov NCT03299218.

Background Burr hole drainage is the criterion standard treatment for chronic subdural hematoma (CSDH), a common neurosurgical condition. However, apart from the surgical technique, the method of anesthesia also has a significant impact on postoperative patient outcome. Currently, there are limited studies comparing the use of local anesthesia with sedation (LA sedation) versus general anesthesia (GA) in the drainage of CSDH. The objective of this study was to compare the morbidity and mortality outcomes of using LA sedation versus GA in CSDH burr hole drainage. Methods This retrospective study presents a total of 257 operations in 243 patients from 2 hospitals. A total of 130 cases were operated under LA sedation in hospital 1 and 127 cases under GA in hospital 2. Patient demographics and presenting features were similar at baseline. Results Values are shown as LA sedation versus GA. Postoperatively, most patients recovered well in both groups with Glasgow Outcome Scale scores of 4–5 (96.2% vs. 88.2%, respectively). The postoperative morbidity was significantly increased by an odds ratio of 5.44 in the GA group compared with the LA sedation group (P = 0.005). The mortality was also significantly higher in the GA group (n = 5, 3.9%) than the LA sedation group (n = 0, 0.0%; P = 0.028). The CSDH recurrence rate was 4.6% in the LA sedation group versus 6.3% in the GA group. No intraoperative conversion from LA sedation to GA was reported. Conclusions This study demonstrates that CSDH drainage under LA sedation is safe and efficacious, with a significantly lower risk of postoperative mortality and morbidity when compared with GA.

Background Stopping renin-angiotensin system inhibitors (RASi) after an episode of hyperkalemia is common but may involve therapeutic compromises, in that the cessation of RASi deprives patients of their beneficial cardiovascular effects. Methods and results Observational study from the Stockholm Creatinine Measurements (SCREAM) project including patients initiating RASi in routine care and surviving a first-detected episode of hyperkalemia (potassium >5.0 mmol/L). We used target trial emulation techniques based on cloning, censoring and weighting to compare stopping vs. continuing RASi within 6 months after hyperkalemia. Outcomes were 3-year risks of mortality, major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction and stroke hospitalization) and recurrent hyperkalemia. Of 5669 new users of RASi who developed hyperkalemia (median age 72 years, 44% women), 1425 (25%) stopped RASi therapy within 6 months. Compared with continuing RASi, stopping therapy was associated with a higher 3-year risk of death (absolute risk difference 10.8%; HR 1.49, 95% CI 1.34-1.64) and MACE (risk difference 4.7%; HR 1.29, 1.14-1.45), but a lower risk of recurrent hyperkalemia (risk difference -9.5%; HR 0.76, 0.69-0.84). Results were consistent for events following potassium of >5.0 or >5.5 mmol/L, after censoring when the treatment decision was changed, across prespecified subgroups, and after adjusting for albuminuria. Conclusion These findings suggest that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but higher risk of death and cardiovascular events.

Background Boys with posterior urethral valves (PUVs) have an increased risk of febrile urinary tract infections (fUTIs). Circumcision is believed to reduce the risk of fUTIs in boys, although there are no randomized trials demonstrating this. Objective To determine the effect of circumcision on the risk of fUTIs in boys with PUVs. Design, setting, and participants A clinical randomized trial that ran between August 2012 and July 2017 was conducted. The trial was multicentric, including 13 referral centers for pediatric urology. Male boys, aged 1–28 d, diagnosed with posterior urethral valves, confirmed by voiding cystogram, were included. The exclusion criteria included presence of a genital malformation contraindicating performing a circumcision. Intervention Participants were randomized to neonatal circumcision + antibiotic prophylaxis (CATB) or antibiotic prophylaxis alone (ATB), and followed for 2 yr. Outcome measurements and statistical analysis The primary outcome was a risk of presenting fUTIs in each group. An fUTI was defined as fever (>38.5 °C) with evidence of pyuria and culture-proven infection on urinalysis, obtained by urethral catheterization or suprapubic aspiration. A bivariate analysis of the primary outcome was performed using the Kaplan-Meier method. Results and limitations In total, 91 patients were included: 49 in group CATB and 42 in group ATB. The probability of presenting an fUTI was 20% in group ATB versus 3% in group CATB. The hazard ratio of presenting an fUTI within 2 yr in the ATB group compared with that in the CATB group was 10.3 (95% confidence interval: 1.3–82.5). Sixty-four children (70.3%) had a complete follow-up at 2 yr of age. Conclusions Circumcision significantly decreases the risk of presenting an fUTI in boys with PUVs. Patient summary In this report, we compared, in a multicentric trial, the number of febrile urinary tract infections (UTIs) in boys with posterior urethral valves who had either antibiotic prophylaxis alone or antibiotic prophylaxis and circumcision. We found that those who had a circumcision had a significantly lower risk of febrile UTIs.

BACKGROUND: Patients on hemodialysis have an elevated risk for COVID-19 but were not included in efficacy trials of SARS-CoV-2 vaccines. METHODS: We conducted a retrospective, observational study to estimate the real-world effectiveness and immunogenicity of two mRNA SARS-CoV-2 vaccines in a large, representative population of adult hemodialysis patients in the United States. In separate, parallel analyses, patients who began a vaccination series with BNT162b2 or mRNA-1273 in January and February 2021 were matched with unvaccinated patients and risk for outcomes were compared for days 1-21, 22-42, and ≥43 after first dose. In a subset of consented patients, blood samples were collected approximately 28 days after the second dose and anti–SARS-CoV-2 immunoglobulin G was measured. RESULTS: A total of 12,169 patients received the BNT162b2 vaccine (matched with 44,377 unvaccinated controls); 23,037 patients received the mRNA-1273 vaccine (matched with 63,243 unvaccinated controls). Compared with controls, vaccinated patients’ risk of being diagnosed with COVID-19 postvaccination became progressively lower during the study period (hazard ratio and 95% confidence interval for BNT162b2 was 0.21 [0.13, 0.35] and for mRNA-1273 was 0.27 [0.17, 0.42] for days ≥43). After a COVID-19 diagnosis, vaccinated patients were significantly less likely than unvaccinated patients to be hospitalized (for BNT162b2, 28.0% versus 43.4%; for mRNA-1273, 37.2% versus 45.6%) and significantly less likely to die (for BNT162b2, 4.0% versus 12.1%; for mRNA-1273, 5.6% versus 14.5%). Antibodies were detected in 98.1% (309/315) and 96.0% (308/321) of BNT162b2 and mRNA-1273 patients, respectively. CONCLUSIONS: In patients on hemodialysis, vaccination with BNT162b2 or mRNA-1273 was associated with a lower risk of COVID-19 diagnosis and lower risk of hospitalization or death among those diagnosed with COVID-19. SARS-CoV-2 antibodies were detected in nearly all patients after vaccination. These findings support the use of these vaccines in this population.

BACKGROUND Evidence of an association between sleep duration and depression was inconsistent. METHODS Adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016 were included. Multivariable logistic regression was used to evaluate the association between sleep duration and depression. RESULTS Among the 25,962 participants (mean age 48.1 years; 49.2% male) in this study, 23,636 had a depression score

BackgroundDetermining the humoral immunogenicity of tozinameran (BNT162b2) vaccine in patients requiring chronic renal replacement therapy, and its impact on COVID-19 morbidity several months after vaccination, will guide risk assessment and subsequent changes in vaccination policy.MethodsIn a prospective post-vaccination cohort study with up to 5 months follow-up we studied outpatient dialysis and kidney transplant patients and respective healthcare teams. Outcomes were anti S1/S2 antibody response to vaccine or infection and infection rate during followup.Results175 dialysis patients (40% women, 65±15 years), 252 kidney transplant patients (33% women, 54±14 years) and 71 controls (65% women, 44±14 years) were followed. Three months or longer after vaccination we detected anti S1/S2 IgG antibodies in 80% of dialysis patients, 44% of transplant recipients and 100% of controls, whereas respective rates after infection were 94%, 75% and 100%. Predictors of non-response were older age, diabetes, history of cancer, lower lymphocyte count and lower vitamin-D levels. Factors associated with lower titers in dialysis patients were modality (hemodialysis vs peritoneal) and high serum ferritin levels. In transplant patients, hypertension and higher calcineurin or mTOR inhibitor drug levels were linked with diminished antibody response. Vaccination associated with fewer subsequent infections (HR=0.23, p10titer (pConclusionsDialysis patients, and more so kidney transplant recipients, mounted reduced antibody response to COVID-19 mRNA vaccination, and lesser humoral response associated with more infections. Measures to identify and protect non-responsive patients are urgently required.SignificanceReports on the humoral immunogenicity of SARS-CoV-2 mRNA vaccines in patients with end stage renal disease are scarce, and association with subsequent COVID-19 morbidity is unknown. In this cohort study that included 175 patients treated with dialysis, 252 kidney transplant recipients and 71 control volunteers, the proportion achieving an antibody response was time- and group-dependent, reaching 80%, 44% and 100% at 3 months post prime inoculation. Personal history of vaccination, positive antibody responses and antibody titers associated with significantly lower risk of COVID-19 infection. Thus, in patients with end stage renal disease, SARS-CoV-2 antibody testing may be warranted after vaccination, to identify non-responders at higher risk for disease.

Introduction Diagnoses of anxiety and/or depression are common in subjects at Ultra-High Risk for Psychosis (UHR) and associated with extensive functional impairment. Less is known about the impact of affective comorbidities on the prospective course of attenuated psychotic symptoms (APS). Method Latent class mixed modelling identified APS trajectories in 331 UHR subjects assessed at baseline, 6, 12, and 24 months follow-up. The prognostic value of past, baseline, and one-year DSM-IV depressive or anxiety disorders on trajectories was investigated using logistic regression, controlling for confounders. Cox proportional hazard analyses investigated associations with transition risk. Results 46.8% of participants fulfilled the criteria for a past depressive disorder, 33.2% at baseline, and 15.1% at one-year follow-up. Any past, baseline, or one-year anxiety disorder was diagnosed in 42.9%, 37.2%, and 27.0%, respectively. Participants were classified into one of three latent APS trajectory groups: (1) persistently low, (2) increasing, and (3) decreasing. Past depression was associated with a higher risk of belonging to the increasing trajectory group, compared to the persistently low (OR = 3.149, [95%CI: 1.298–7.642]) or decreasing group (OR = 3.137, [1.165–8.450]). In contrast, past (OR = .443, [.179–1.094]) or current (OR = .414, [.156–1.094]) anxiety disorders showed a trend-level association with a lower risk of belonging to the increasing group compared to the persistently low group. Past depression was significantly associated with a higher risk of transitioning to psychosis (HR = 2.123, [1.178–3.828]). Conclusion A past depressive episode might be a particularly relevant risk factor for an unfavorable course of APS in UHR individuals. Early affective disturbances may be used to advance detection, prognostic, and clinical strategies.

Objective To test whether the presence of structural entheseal lesions in psoriasis patients influences the risk for the progression to psoriatic arthritis (PsA). Methods Prospective cohort study on psoriasis patients without clinical evidence of musculoskeletal involvement receiving baseline assessment of structural entheseal lesions and volumetric bone mineral density (vBMD) at entheseal and intra-articular sites by high-resolution peripheral quantitative computed tomography (HR-pQCT). Adjusted relative risks of developing PSA associated with baseline volumetric bone density and the presence of structural entheseal lesions were calculated using multivariable Cox regression models. Results The cohort included 114 psoriasis patients (M/F 72/42) with a mean (SD) follow-up duration of 28.2 (17.7) months, during which 24 patients developed PsA (9.7 /100 patient-years, 95%CI 6.2 to 14.5). Patients with structural entheseal lesions were at higher risk of developing PsA compared to patients without such lesions (21.4/100 patient-years, 95%CI 12.5 to 34.3, HR 5.10, 95%CI 1.53 to 16.99, p=0.008). With respect to vBMD, a 1-standard deviation increase in entheseal, but not intra-articular vBMD was associated with an approximate 30% reduced risk to progress to PsA. Especially, higher cortical vBMD at entheseal segments was associated with a lower risk of developing PsA (HR 0.32 per SD, 95%CI 0.14 to 0.71), and remained robust after multiple imputation of missing data (HR 0.64, 95%CI 0.42 to 0.98). Conclusion Presence of structural entheseal lesions as well as low cortical vBMD at entheseal segments are associated with an increased risk of developing PsA in patients with psoriasis.

To investigate the effect of biologic treatments for psoriasis on the incidence of psoriatic arthritis (PsA).This retrospective cohort study was conducted using electronic medical records from a large health maintenance organization. Patients who received biologic treatment for psoriasis and were not diagnosed as having PsA before or at the time of biologic treatment initiation were included. Control psoriasis patients who did not receive biologic treatment were matched by age at time of diagnosis, sex, time from psoriasis diagnosis until treatment initiation, maximum body mass index, and smoking status. The groups were different in most characteristics. Therefore, propensity score matching was implemented. Log rank test and multivariable Cox proportional hazards regression were used to compare the groups.Overall, 1,326 patients were included, of whom 663 had received biologic treatment and 663 had not. The Kaplan-Meier curve for the propensity score-matched groups reflected a statistically significant increased risk for PsA among the control group compared to the biologic treatment group. The results of the multivariable Cox regression showed that the control group had a significantly higher risk for PsA compared to the biologic treatment group within 10 years of follow-up (adjusted hazard ratio 1.39 [95% confidence interval 1.03-1.87]).Our findings show a statistically and clinically significant decreased risk for developing PsA among patients with psoriasis who receive biologic treatments. The results suggest that biologic medications should be considered for patients who present with significant risk factors for PsA at an earlier stage of treatment.

Background Cachexia, characterized by involuntary muscle mass loss, negatively impacts survival outcomes, treatment tolerability, and functionality in cancer patients. However, there is a limited appreciation of the true prevalence of low muscle mass due to inconsistent diagnostic methods and limited oncologist awareness. Methods Twenty-nine French healthcare establishments participated in this cross-sectional study, recruiting patients with those metastatic cancers most frequently encountered in routine practice (colon, breast, kidney, lung, prostate). The primary outcome was low skeletal muscle mass prevalence, as diagnosed by estimating the skeletal mass index (SMI) in the middle of the third-lumbar vertebrae (L3) level via computed tomography (CT). Other objectives included an evaluation of nutritional management, physical activity, and toxicities related to ongoing treatment. Results Seven hundred sixty-six patients (49.9% males) were enrolled with a mean age of 65.0 years. Low muscle mass prevalence was 69.1%. Only one-third of patients with low skeletal muscle mass were receiving nutritional counselling and only 28.4% were under nutritional management (oral supplements, enteral or parenteral nutrition). Physicians highly underdiagnosed those patients identified with low skeletal muscle mass, as defined by the primary objective, by 74.3% and 44.9% in obese and non-obese patients, respectively. Multivariate analyses revealed a lower risk of low skeletal muscle mass for females (OR: 0.22, P 0.01) and those without brain metastasis (OR: 0.34, P 0.01). Low skeletal muscle mass patients were more likely to have delayed treatment administration due to toxicity (11.9% versus 6.8%, P = 0.04). Conclusions There is a critical need to raise awareness of low skeletal muscle mass diagnosis among oncologists, and for improvements in nutritional management and physical therapies of cancer patients to curb potential cachexia. This calls for cross-disciplinary collaborations among oncologists, nutritionists, physiotherapists, and radiologists.

BACKGROUND/PURPOSE To characterize the nature of posterior segment ocular injuries in combat trauma. METHODS Eyes in the Walter Reed Ocular Trauma Database were evaluated for the presence of posterior segment injury. Final visual outcomes in open-globe versus closed-globe injuries and by zone of injury and the types of posterior segment injuries in open-globe versus closed-globe injuries were assessed. RESULTS Four hundred fifty-two of 890 eyes (50.8%) had at least one posterior segment injury. The mechanism of injury was most commonly an improvised explosive device in 280 (62.0%) eyes. Sixty-one patients (13.5%) had a Zone I injury, 50 (11.1%) a Zone II injury, and 341 (75.4%) a Zone III injury. Patients with Zone I injuries were more likely to have a final visual acuity of 20/200 or better compared with patients with either a Zone II (P < 0.001) or Zone III injury (P = 0.007). Eyes with a closed-globe injury were more likely to have a final visual acuity of 20/200 or better compared with those with an open-globe injury (P < 0.001). Furthermore, closed-globe injury compared with open-globe injury had a lower risk of vitreous hemorrhage (odds ratio 0.32, P < 0.001), proliferative vitreoretinopathy (odds ratio 0.14, P < 0.001), and retinal detachment (odds ratio 0.18, P < 0.001) but a higher risk of chorioretinal rupture (odds ratio 2.82, P < 0.001) and macular hole (odds ratio 3.46, P = 0.004). CONCLUSION Patients with combat ophthalmic trauma had similar posterior segment injury patterns to civilian trauma in open-globe versus closed-globe injuries. Zone II and III injuries were associated with a worse visual prognosis.

Background Prior reports demonstrate the expression of estrogen and progesterone receptors in high-grade gliomas (HGGs), but the relationship between hormone receptor-positive disease and risk of HHGs in patients with breast cancer (BC) remains uncharacterized. Methods Using the SEER 18 registries (2000–2017), we examined the temporal trend of the incidence of HGGs and BC. The standardized incidence ratio was calculated to assess the risk of subsequent HGG in BC patients. Results During the study period, the incidence of BC and HGGs remained comparable for men and women. Among 976,134 patients with BC, we found a decreased incidence of HGGs in females, but not in males. Female BC patients with hormone receptor-positive disease were at a lower risk of developing glioblastoma and anaplastic astrocytoma. Conclusion Our study findings allude to the protective role of hormone exposure in the development of HGGs, which may lead to the development of therapies targeting hormonal pathways.

Objective To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in people with type 1 diabetes at high risk of cardiovascular disease. Design Prospective cohort study. Methods One hundred and ninety-five people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results In 195 individuals (median follow-up 12.9 years, IQR 6.7–17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR: 0.75; 95% CI: 0.61–0.91), a lower risk of cardiovascular events and vascular interventions (HR: 0.74; 95% CI: 0.63–0.87) and a lower risk of all-cause mortality (HR: 0.81; 95% CI: 0.67–0.98). Conclusions Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.

BACKGROUND Inhibition of the renin angiotensin aldosterone system (RAAS) improves survival and reduces adverse cardiac events in heart failure with reduced ejection fraction, but the benefit is not well-defined following left ventricular assist device (LVAD). METHODS We analyzed the ISHLT IMACS registry for adults with a primary, continuous-flow LVAD from January 2013 to September 2017 who were alive at postoperative month 3 without a major adverse event, and categorized patients according to treatment an angiotensin converting enzyme inhibitor (ACEI/ARB) or mineralocorticoid receptor antagonist (MRA). Propensity score matching was performed separately for ACEI/ARB vs none (n = 4,118 each) and MRA vs none (n = 3,892 each). RESULTS Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (p < 0.001) but not MRA (p = 0.31). In Cox proportional hazards analyses adjusted for known predictors of mortality following LVAD, ACEI/ARB use (hazard ratio 0.81 [95% confidence interval 0.71-0.93], p < 0.0001) but not MRA use (hazard ratio 1.03 [95% confidence interval 0.88-1.21], p = 0.69) was independently associated with lower mortality. Among patients treated with an ACEI/ARB, there was a significantly lower unadjusted risk of cardiovascular death (p < 0.001), risk of gastrointestinal bleeding (p = 0.01), and creatinine level (p < 0.001). MRA therapy was associated with lower risk of gastrointestinal bleeding (p = 0.01) but higher risk of hemolysis (p < 0.01). Potential limitations include residual confounding and therapy crossover. CONCLUSION These findings suggest a benefit for ACEI/ARB therapy in patients with heart failure after LVAD implantation.

Aims The aim of this study was to determine if uncemented acetabular polyethylene (PE) liner geometry, and lip size, influenced the risk of revision for instability or loosening. Methods A total of 202,511 primary total hip arthroplasties (THAs) with uncemented acetabular components were identified from the National Joint Registry (NJR) dataset between 2003 and 2017. The effect of liner geometry on the risk of revision for instability or loosening was investigated using competing risk regression analyses adjusting for age, sex, American Society of Anesthesiologists grade, indication, side, institution type, surgeon grade, surgical approach, head size, and polyethylene crosslinking. Stratified analyses by surgical approach were performed, including pairwise comparisons of liner geometries. Results The distribution of liner geometries were neutral (39.4%; 79,822), 10° (34.5%; 69,894), 15° (21.6%; 43,722), offset reorientating (2.8%; 5705), offset neutral (0.9%; 1,767), and 20° (0.8%; 1,601). There were 690 (0.34%) revisions for instability. Compared to neutral liners, the adjusted subhazard ratios of revision for instability were: 10°, 0.64 (p < 0.001); 15°, 0.48 (p < 0.001); and offset reorientating, 1.6 (p = 0.010). No association was found with other geometries. 10° and 15° liners had a time-dependent lower risk of revision for instability within the first 1.2 years. In posterior approaches, 10° and 15° liners had a lower risk of revision for instability, with no significant difference between them. The protective effect of lipped over neutral liners was not observed in laterally approached THAs. There were 604 (0.3%) revisions for loosening, but no association between liner geometry and revision for loosening was found. Conclusion This registry-based study confirms a lower risk of revision for instability in posterior approach THAs with 10° or 15° lipped liners compared to neutral liners, but no significant difference between these lip sizes. A higher revision risk is seen with offset reorientating liners. The benefit of lipped geometries against revision for instability was not seen in laterally approached THAs. Liner geometry does not seem to influence the risk of revision for loosening. Cite this article: Bone Joint J 2021;103-B(12):1774–1782.

Background: Physical activity (PA) and discretionary screen time (DST; television and computer use during leisure) are both associated with obesity risk, but little longitudinal evidence exists on their combined influence. This study examined the independent and joint associations of changes in PA and DST with incident obesity, body mass index (BMI) and waist circumference (WC). Methods: We analysed the data of individuals aged 40–69 years from the UK Biobank, a large-scale, population-based prospective cohort study. PA was measured using the International Physical Activity Questionnaire and DST was defined as the total of daily TV viewing and non-occupational computer use. Changes in PA and DST over time were defined using departure from sex-specific baseline tertiles and categorised as worsened (PA decreased/DST increased), maintained, and improved (PA increased/DST decreased). We then used each exposure change to define a joint PA-DST change variable with nine mutually exclusive groups. We used multivariable adjusted mixed-effects linear and Poisson models to examine the independent and joint associations between PA and DST changes with BMI and WC and incident obesity, respectively. Development of a BMI ≥ 30 kg/m2 was defined as incident obesity. Results: Among 30,735 participants, 1,628 (5.3%) developed incident obesity over a mean follow-up of 6.9 (2.2) years. In the independent association analyses, improving PA (Incident Rate Ratio (IRR) 0.46 (0.38–0.56)) was associated with a lower risk of incident obesity than maintaining PA, maintaining DST, or improving DST. Compared to the referent group (both PA and DST worsened), all other combinations of PA and DST changes were associated with lower incident obesity risk in the joint association analyses. We observed substantial beneficial associations in the improved PA groups, regardless of DST change [e.g., DST worsened (IRR 0.31 (0.21–0.44)), maintained (IRR 0.34 (0.25–0.46)), or improved (IRR 0.35 (0.22–0.56)]. The most pronounced decline in BMI and WC was observed when PA was maintained or improved and DST was maintained. Conclusion: We found that improved PA had the most pronounced beneficial associations with incident obesity, irrespective of DST changes. Improvements in PA or DST mutually attenuated the deleterious effects of the other behaviour’s deterioration.

AimsTo examine the temporal trends and factors associated with national cardiac rehabilitation (CR) referral and compare the risk of hospital readmission and mortality in those referred for CR versus no referral.Methods and resultsThis cohort study includes all adult patients alive 120 days from incident heart failure (HF) identified by the Danish Heart Failure Registry (n = 33 257) between 2010 and 2018. Multivariable logistic regression models were used to assess the association between CR referral and patient factors and acute all-cause hospital readmission and mortality at 1 year following HF admission. Overall, 46.7% of HF patients were referred to CR, increasing from 31.7% in 2010 to 52.2% in 2018. Several factors were associated with lower odds of CR referral: male sex [odds ratio (OR): 0.85; 95% confidence interval: 0.80–0.89], older age, unemployment, retirement, living alone, non-Danish ethnic origin, low educational level, New York Heart Association (NYHA) class IV vs. I (OR: 0.75; 0.60–0.95), left ventricular ejection fraction >40%, and comorbidity (stroke, chronic kidney disease, atrial fibrillation/flutter, and diabetes). Myocardial infarction, arthritis, coronary artery bypass grafting, percutaneous coronary intervention, valvular surgery, NYHA class II, and use of angiotensin-converting enzyme inhibitors were associated with higher odds of CR referral. CR referral was associated with lower risk of acute all-cause readmission (OR: 0.92; 0.87–0.97) and all-cause mortality (OR: 0.65; 0.58–0.72).ConclusionAlthough increased over time, only one in two HF patients in Denmark were referred to CR in 2018. Strategies are needed to reduce referral disparities, focusing on subgroups of patients at highest risk of non-referral.

Background Breakthrough coronavirus disease 2019 (COVID-19) may occur in fully vaccinated persons. Methods We assessed the clinical outcomes of breakthrough COVID-19 in fully vaccinated individuals. Results In this cohort of 1395 persons (mean age, 54.3 years; 60% female; median body mass index, 30.7) who developed breakthrough COVID- 19, there were 107 (7.7%) who required hospitalization by day 28. Hospitalization was significantly associated with the number of medical comorbidities. Antispike monoclonal antibody treatment was significantly associated with a lower risk of hospitalization (odds ratio, 0.227; 95% confidence interval, 0.128–0.403; P < .001). The number needed to treat (NNT) to prevent 1 hospitalization was 225 among the lowest risk patient group compared with NNT of 4 among those with highest numbers of medical comorbidity. Conclusions Monoclonal antibody treatment is associated with reduced hospitalization in vaccinated high-risk persons with mild to moderate COVID-19.

We examined the association of iso-osmolar contrast media (IOCM) versus low-osmolar contrast media (LOCM) with major adverse renal, cardiovascular, or limb events in patients at high-risk of acute kidney injury (AKI) undergoing peripheral endovascular procedures.Procedural characteristics including iodinated contrast type and volume have been associated with adverse renal and cardiovascular outcomes in patients undergoing angiographic interventions.Patients at high-risk of AKI, undergoing peripheral endovascular procedures were identified using the Premier Healthcare Database and separated into claudication and critical limb ischemia (CLI) cohorts. For each cohort, we compared IOCM versus LOCM for the primary endpoint of MARCE (major adverse renal or cardiovascular events) and secondary endpoints of major adverse renal events (MARE) and major adverse renal and limb events (MARLE). These outcomes were captured within the indexed hospitalization via adjusted multivariable regression analyses.Two procedure-based cohorts of high-risk patients were formed: claudication (N = 11,976) and CLI (N = 8713). Use of IOCM was associated with a significant absolute risk reduction (ARR) of 2.2% (p 0.0001) for MARCE overall and in each cohort (claudication, 1.8%, p = 0.0070; CLI, 2.7%, p = 0.0054). The incidence of MARE and MARLE in the overall cohort was also lower with the use of IOCM: MARE (ARR = 1.4%, p = 0.0072) and MARLE (ARR = 2.0%, p = 0.0043).Using IOCM versus LOCM in patients at high-risk of adverse renal events undergoing peripheral endovascular procedures was independently associated with lower risk of MARCE, MARE, and MARLE.

Background: The associations of changes in noncombustible nicotine or tobacco product (NNTP) and combustible cigarette (CC) use habits with subsequent cardiovascular disease (CVD) risk are still unclear. Methods: The study population consisted of 5 159 538 adult men who underwent health screening examinations during both the first (2014–2015) and second (2018) health screening periods from the Korean National Health Insurance Service database. All participants were divided into continual CC-only smokers, CC and NNTP users, recent ( Results: Compared with continual CC-only smokers, CC and NNTP users (aHR, 0.83 [95% CI, 0.79–0.88]) and initial CC smokers who quit CCs and switched to NNTP use only (recent CC quitters with NNTP use, aHR, 0.81 [95% CI, 0.78–0.84]) had lower risk for CVD. After propensity score matching, recent CC quitters with NNTP use (aHR, 1.31 [95% CI, 1.01–1.70]) had higher risk for CVD than recent CC quitters without NNTP use. Similarly, compared with long-term CC quitters without NNTP use, long-term CC quitters with NNTP use (aHR, 1.70 [95% CI, 1.07–2.72]) had higher CVD risk. Conclusions: Switching to NNTP use among initial CC smokers was associated with lower CVD risk than continued CC smoking. On CC cessation, NNTP use was associated with higher CVD risk than CC quitting without NNTPs. Compared with CC smokers who quit without NNTP use, CC quitters who use NNTPs may be at higher future CVD risk.

We analysed long-term outcome of patients receiving haematopoietic allogeneic stem cell transplantation (allo-HSCT) as a first transplant for high-risk Hodgkin lymphoma (HL). One hundred and ninety patients were included in this study, 63% of them had previously received brentuximab vedotin and/or checkpoint inhibitors. Seventy patients (37%) received an unrelated donor allo-HSCT, 99 (51%) had myeloablative conditioning (MAC) and 60% had in vivo T-cell/depleted grafts (TCD). The 100-day cumulative incidence (CI) of grade II-IV acute graft-versus-host disease (GVHD) was 25% and the 3-year CI of chronic GVHD was 38%. The 3-year CI of non-relapse mortality (NRM) and relapse rate were 21% and 38% respectively. After a median follow-up of 58 months, 3-year overall survival (OS) and progression-free survival (PFS) were 58% and 41% respectively. Multivariate analysis showed that, in comparison to reduced-intensity conditioning regimens with or without TCD, MAC using TCD had similar NRM and a lower risk of relapse leading to significantly better OS and PFS. MAC without TCD was associated with higher NRM and worse survival outcomes. These results suggest that in patients with high-risk HL and candidates of allo-HSCT, a MAC strategy with TCD might be the best option.

The incidence of invasive fungal infection (IFI) in patients with acute myeloid leukemia (AML) has decreased with the introduction of antimold prophylaxis. Although acute lymphoblastic leukemia (ALL) has a lower risk of IFI than does AML, the incidences of IFI in both AML and ALL in the era of antimold prophylaxis should be re-evaluated. We analyzed adults with AML or ALL who had undergone induction, re-induction, or consolidation chemotherapy from January 2017 to December 2019 at Seoul National University Hospital. Their clinical characteristics during each chemotherapy episode were reviewed, and cases with proven or probable diagnoses were regarded as positive for IFI. Of 552 episodes (393 in AML and 159 in ALL), 40 (7.2%) were IFI events. Of the IFI episodes, 8.1% (12/148) and 5.9% (13/220) (P = 0.856) occurred in cases of ALL without antimold prophylaxis and AML with antimold prophylaxis, respectively. After adjusting for clinical factors, a lack of antimold prophylaxis (adjusted odds ratio [aOR], 3.52; 95% confidence interval [CI], 1.35–9.22; P = 0.010) and a longer duration of neutropenia (per one day, aOR, 1.02; 95% CI, 1.01–1.04; P = 0.001) were independently associated with IFI. In conclusion, the incidence of IFI in ALL without antimold prophylaxis was not lower than that in AML. A lack of antimold prophylaxis and prolonged neutropenia were independent risk factors for IFI. Clinicians should be on guard for detecting IFI in patients with ALL, especially those with risk factors.

Aims Little is known about the characteristics and outcomes of patients who undergo coronary angiography during heart failure (HF) hospitalization, as well as those with coronary stenosis, and those who underwent coronary revascularization. Methods and results We analysed 2163 patients who were hospitalized for HF without acute coronary syndrome or prior HF hospitalization. We compared patient characteristics and 1 year clinical outcomes according to (i) patients with versus without coronary angiography, (ii) patients with versus without coronary stenosis, and (iii) patients with versus without coronary revascularization. The primary outcome measure was the composite of all‐cause death or HF hospitalization. Coronary angiography was performed in 37.0% of patients. In the multivariable logistic regression analysis, factors independently associated with coronary angiography were age

Background Higher flavonoid intakes are hypothesised to confer protection against type 2 diabetes mellitus. Objective We aimed to 1) investigate associations between flavonoid intakes and diabetes, 2) examine the mediating impact of body fat, and 3) identify subpopulations that may receive the greatest benefit from higher flavonoid intakes in participants of the Danish Diet, Cancer, and Health Study followed-up for 23 years. Design Cross-sectional associations between baseline flavonoid intake, estimated using food frequency questionnaires and the Phenol Explorer database, and body fat estimated by bioelectrical impedance, were assessed using multivariable-adjusted linear regression models. Non-linear associations between flavonoid intake and incident diabetes were examined using restricted cubic splines with multivariable-adjusted Cox proportional hazards models. Results Among 54,787 participants (median [IQR] age of 56 [52-60] years; (47.3%) men), 6700 individuals were diagnosed with diabetes. Participants in the highest total flavonoid intake quintile (median, 1,202 mg/d) had a 1.52 kg lower body fat (95%CI: -1.74, -1.30) and a 19% lower risk of diabetes [hazard ratio (95%CI): 0.81 (0.75, 0.87)] after multivariable adjustments and compared to participants in the lowest intake quintile (median, 174 mg/d). Body fat mediated 57% (95% CI: 42%, 83%) of the association between flavonoid intake and incident diabetes. Of the flavonoid subclasses, moderate to high intakes of flavonols, flavanol monomers, flavanol oligo + polymers, and anthocyanins were significantly associated with a lower risk of diabetes. While associations were not modified by sex, smoking status, BMI or physical activity (pinteraction > 0.05 for all), findings on an absolute scale suggest that those at a higher risk (those with obesity) may benefit the most from a higher flavonoid intake. Conclusions These findings suggest that a diet abundant in flavonoid-rich foods may help to ameliorate diabetes risk, in part through a reduction in body fat.

OBJECTIVES This study aims to analyze the functional results, management, and complications of acute Seymour fracture treatment and to generalize the understanding of Seymour fractures, as well as awareness about its controversial treatment and critical sequelae. PATIENTS AND METHODS Between January 1994 and December 2019, a total of 29 patients (20 males, 9 females; mean age: 7.9±3.9 years; range, 1 to 15 years) who presented within the first 24 h of injury and were diagnosed with Seymour fractures and treated in the emergency setting were retrospectively analyzed. Clinical and radiological data were collected from medical records at the time of diagnosis and during follow-up, within a week after the treatment and in the visits required until fracture healing, and no sequelae were observed. In the event of complications, a minimum of one year of follow-up was carried out. Radiographs were taken of the anteroposterior and lateral views during each visit. RESULTS The mean follow-up was 10.8±8.6 (range, 2 to 36) months. Surgical treatment in the operating room was performed in 24 (82.7%) patients using a single longitudinal Kirschner wire (K-wire) fixation through the distal phalanx and the distal interphalangeal joint in 21 patients. Non-operative treatment based on closed reduction and splinting was performed in five (17.3%) patients. There was no statistically significant difference in the final passive range of motion and physeal growth arrest in relation to the use or non-use of K-wires. The use of antibiotics in any of the three possible administrations (intravenous antibiotic regimen, intravenous and later oral antibiotic at-home or oral antibiotics), in relation to the non-use of antibiotics seemed to be a protective factor against infections (odds ratio=0.04; 95% confidence interval: 0.006-0.2; p=0.001). CONCLUSION The identification of Seymour fractures is crucial for applying the correct treatment and reducing the risk of complications, such as osteomyelitis and physeal alterations. Based on our study results, we can suggest that the use of an antibiotic regimen causes a lower risk of infections in acute Seymour fractures. The prompt identification of these fractures with a standardized protocol covering irrigation, debridement, reduction, fixation, and prophylactic antibiotics is needed to avoid complications.

Background and aims The association between serum uric acid (SUA) and the all-cause and cardiovascular diseases (CVD) mortality remains controversial, but few studies based on the community population in Shanghai have been reported. We aimed to evaluate the association of SUA level with all-cause and CVD mortality in Chinese elderly based on a community-based cohort study in Shanghai of China. Methods and results A total of 12,071 eligible participants were included, with a cumulative follow-up period of 46,063.65 person-years and a median of 4.67 years. The time-dependent Cox regression model indicated that when SUA level was classified into quartile groups, no significant association was observed between SUA level and all-cause death in both men and women and between SUA level and CVD mortality in men. However, the HR (95%CI) between SUA groups and CVD death in women was 3.75 (1.49–9.43) for quartile 1, 3.66 (1.53–8.76) for quartile 2, and 2.98 (1.33–6.69) for quartile 4, respectively, when compared with the quartile 3 SUA level. A significant non-linear association was observed between SUA level and CVD death in elderly women. An increased risk of CVD death was observed among women with SUA level less than 4.30 mg/dL at the baseline, and a lower risk, among women with SUA level of 4.30–4.72 mg/dL at the baseline. Conclusion The non-linear association between SUA level and CVD mortality in elderly women suggests a potential benefit of controlling SUA level at4.30–4.72 mg/dL in elderly Chinese women.

Aims Risk factors for asymptomatic echocardiographic abnormalities that predict symptomatic heart failure (HF) may provide insight into early mechanisms of HF pathogenesis. We examined risk factors associated with asymptomatic echocardiographic structural, systolic, and diastolic abnormalities, separately and in combination, and interactions between risk factors, in the prospective community‐based SCReening Evaluation of the Evolution of New HF (SCREEN‐HF) Study cohort of 3190 participants at increased risk of cardiovascular disease. Methods and results Inclusion criteria were age ≥ 60 years with one or more of hypertension, diabetes, ischaemic heart disease, valvular heart disease, abnormal heart rhythm, cerebrovascular disease, or renal impairment. Exclusion criteria were known HF, ejection fraction mild valve abnormality. Structural, systolic, and diastolic echocardiographic abnormalities were defined according to the Atherosclerosis Risk in Communities study criteria, and risk factors for asymptomatic structural, systolic, and diastolic abnormalities were identified using logistic regression analysis. In multivariable analysis, increased body mass index (BMI), non‐steroidal anti‐inflammatory drug therapy, and alcohol intake were risk factors for isolated structural abnormality, whereas male gender, increased heart rate, atrial fibrillation (AF), angiotensin‐converting enzyme inhibitor therapy, and obstructive sleep apnoea were associated with a lower risk. Moreover, male gender, smoking, increased systolic blood pressure, and physical inactivity were risk factors for isolated systolic abnormality, whereas increased pulse pressure and antihypertensive therapy were associated with a lower risk. Furthermore, increased age, blood pressure, amino‐terminal pro‐B‐type natriuretic peptide level, and warfarin therapy (associated with AF) were risk factors for isolated diastolic abnormality, whereas increased heart rate and triglyceride level (associated with BMI) were associated with a lower risk. The association of increased heart rate with lower risk of structural and diastolic abnormalities was independent of β‐blocker therapy. Interactions between risk factors differed for structural, systolic, and diastolic abnormalities. Conclusions The different risk factors for asymptomatic structural, systolic, and diastolic abnormalities that predict symptomatic HF, and the interactions between risk factors, illustrate how these structural, systolic, and diastolic abnormalities represent unique trajectories that lead to symptomatic HF. Improved understanding of these trajectories may assist in the design of HF prevention strategies.

Summary Background & aims Type 2 diabetes prevention diet confers a lower risk of type 2 diabetes, which exhibits overlapping mechanisms with pancreatic cancer. We performed a prospective study to examine whether adherence to this dietary pattern is associated with a reduced risk of pancreatic cancer. Methods A population-based cohort of 101,729 American adults was identified. A dietary diabetes risk reduction score was computed to reflect adherence to this dietary pattern, with higher scores representing greater adherence. Cox regression was used to compute hazard ratios (HRs) for pancreatic cancer incidence. Prespecified subgroup analyses were used to identify the potential effect modifiers. Results After an average follow-up of 8.86 years (900,871.67 person-years), a total of 402 pancreatic cancer cases were observed. In the fully adjusted model, participants in the highest quartile of dietary diabetes risk reduction score were found to have a reduced risk of pancreatic cancer compared with those in the lowest quartile [HRquartiles 4 versus 1: 0.62; 95% confidence interval (CI): 0.44, 0.86; Ptrend = 0.004], which remained in a series of sensitivity analyses. Subgroup analyses further found that this favorable association was more pronounced in current or former smokers (HRquartiles 4 versus 1: 0.48; 95% CI: 0.30, 0.77) than in never smokers (HRquartiles 4 versus 1: 0.71; 95% CI: 0.44, 1.15), although the interaction test did not reach statistical significance (Pinteraction = 0.095). Conclusions Greater adherence to type 2 diabetes prevention diet is associated with a lower risk of pancreatic cancer in this US population. More studies are needed to confirm our findings.

Background Early and timely fluid treatment or resuscitation are the basic measures for the active treatment of sepsis. Our aim is to further explore the relationship between fluid balance and prognosis in patients with sepsis on a daily basis for 5 days. Methods Sepsis patients in eICU Collaborative Research Database were divided into the negative balance group (NB/−) and the positive balance group (PB/+) according to daily fluid balance. The primary outcome was in-hospital mortality. Survival differences between the groups were analyzed by using Cox regression. Then dose-response relationship between fluid balance and in-hospital mortality was studied using restricted cubic splines (RCSs). Furthermore, patients with fluid balance data for the previous three consecutive days were selected and divided into eight groups (“+/+/+”, “+/+/−”, “+/ −/−”, “+/ −/+”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−”). Kaplan–Meier curves and Cox regression were used to show the survival difference between groups. Results Our study, which included 19,557 patients in a multicenter database, showed that positive fluid balances on days 1, 2, and 3 after sepsis diagnosis were associated with poor prognosis with the HRs of 1.29 (1.20,1.40), 1.13 (1.01,1.27), and 1.25 (1.08,1.44), respectively, while the fluid balance on days 4 and 5 had no effect on the primary outcome. Then RCSs showed an overall trend that the risk of in-hospital mortality on days 1, 2, and 3 increased with increasing fluid balance. For three consecutive days of fluid balance, we studied 9205 patients and Kaplan–Meier curves revealed survival differences among patients in the eight groups. The cox model demonstrated that compared with the “+/+/+” group, the “+/ −/−”, “−/ −/−”, “−/ −/+”, “−/+/+”, and “−/+/−” groups had a lower risk of in-hospital mortality, with HRs of 0.65 (0.45,0.93), 0.72 (0.60,0.86), 0.63 (0.43,0.93), 0.69 (0.48,0.98), and 0.63 (0.42,0.96), respectively. Conclusions In patients with sepsis, positive fluid balance on days 1, 2, and 3 was associated with adverse outcomes. For patients with fluid balance for three consecutive days, the “+/−/−”, “−/ −/−”, “−/−/+”, “−/+/+”, and “−/+/−” groups were less likely to die in hospital than the “+/+/+” group.

BACKGROUND: Acute and chronic forms of lung allograft injury are associated with specific respiratory pathogens. Donor-derived cell free DNA (ddcfDNA) has been shown to be elevated with acute lung allograft injury and predictive of long-term outcomes. We examined the %ddcfDNA values at times of microbial isolation from bronchoalveolar lavage (BAL). METHODS: Two hundred and six BAL samples from 51 Lung Transplant Recipients (LTRs) with concurrently available plasma %ddcfDNA were analyzed along with microbiology and histopathology. Microbial species were grouped into bacterial, fungal, and viral and “higher risk” and “lower risk” cohorts based on historical association with downstream allograft dysfunction. Analyses were performed to determine pathogen category association with %ddcfDNA, independent of inter-subject variability. RESULTS: Presence of microbial isolates in BAL was not associated with elevated %ddcfDNA compared to samples without isolates. However, “higher risk” bacterial and viral microbes showed greater %ddcfDNA values than lower risk species (1.19% vs. 0.65%, p < 0.01), independent of inter-subject variability. Histopathologic abnormalities concurrent with pathogen isolation were associated with higher %ddcfDNA compared to isolation episodes with normal histopathology (medians 1.23% and 0.66%, p = 0.05). Assessments showed no evidence of correlation between histopathology or bronchoscopy indication and presence of higher risk vs. lower risk pathogens. CONCLUSION: %ddcfDNA is higher among cases of microbial isolation with concurrent abnormal histopathology and with isolation of higher risk pathogens known to increase risk of allograft dysfunction. Future studies should assess if %ddcfDNA can be used to stratify pathogens for risk of CLAD and identify pathogen associated injury prior to histopathology.

Objectives Bridge employment has been encouraged by many countries worldwide as societies age rapidly. However, the health impact on bridge employment is not consistent in previous studies. This study aims to explore the association between bridge employment and long-term health outcome among the Chinese population. Methods In this prospective cohort study, we used a subset of the China Kadoorie Biobank study, in which 163,619 participants who reached the statutory age of retirement at baseline (2004–2008) were included in this study. Mortality statistics were obtained from death registries in the Death Surveillance Points system annually. We used a Cox proportional hazard model to analyze the association between bridge employment and all-cause mortality. Results Overall, we found that compared to retired/nonemployed men and women, hazards of all-cause mortality were lower in older people with bridge employment (men: 0.82, 95% confidence interval [CI]: 0.77–0.88; women: 0.79, 95% CI: 0.74–0.94) in healthy populations. The protective effect of bridge employment was stronger among older adults living in rural areas and among those from a relatively low socioeconomic status. Discussion The lower risk of all-cause mortality associated with bridge employment was consistently observed among older men and women. Our findings may provide important insights from the health dimension on the retirement policy-making in China as a hyper-aging society.

Objective To examine health care utilization among patients with knee osteoarthritis (OA) and assess whether utilization differs among residents of regions with high and low rates of total knee arthroplasty (TKA). Methods This was a retrospective cohort study of US Medicare beneficiaries with knee OA enrolled from 2005 to 2010. Health care utilization data for knee complaints, including rates of physician visits, physical therapy, knee injections, and arthroscopy, were abstracted from claims files until time of TKA or the end of the study in 2015. Utilization was compared among beneficiaries who lived in regions with high or low rates of TKA. Results Among 988,570 beneficiaries with knee OA, 327,499 (33.1%) underwent TKA during follow-up (median 5.6 years). Higher frequency of visits for knee complaints was associated with increased risk of TKA, whereas physical therapy, specialist care, and intraarticular treatments were associated with lower risk of TKA. Frequency of TKA varied from 26.4% in the lowest regional TKA rate quintile to 42.1% in the highest regional TKA rate quintile. Rates of physician visits, physical therapy, specialist care, and treatment with intraarticular injections varied inversely with regional TKA rate quintile. For example, 32.5% of beneficiaries in the lowest region quintile and 23.6% in the highest region quintile underwent physical therapy. Across all quintiles, physical therapy was associated with lower TKA rates. Conclusion Dedicated nonsurgical OA care was infrequently used to treat elderly Americans with knee OA. Nonsurgical care was more common in regions with low TKA rates, suggesting reciprocal emphasis on medical treatment compared to surgical treatment across regions.

To assess incidence and relative risk of cancer in Sweden, by HIV status, from 1988 to 2017.Population-based register study.From the Swedish Total Population Register, all people born between 1940 and 2000 (n = 8 587 629), and resident in Sweden sometime 1983-2017 were identified and linked to National HIV Register InfCareHIV, National Cancer Register, and LISA database. We present incidence and adjusted hazard ratios (adjHR) of infection and noninfection-related cancer for three periods between 1988 and 2017.Incidence and relative risk of infection-related cancer decreased but remained higher in people with HIV (PWH) than in HIV-negative. The proportion attributable to infection remained higher in PWH than in HIV-negative (44 vs. 9%). Women with HIV had lower risk of infection-related cancer than men with HIV [adjusted hazard ratio (adjHR) 0.6, 95% CI 0.4-0.9], mainly driven by lower incidence of Kaposi's sarcoma (adjHR 0.1, 95% CI 0.0-0.4). Current viral suppression (adjHR 0.3, 95% CI 0.2-0.5) was associated with lower risk of infection-related cancer. Current CD4+ cell count less than 200 cells/μl was associated with both infection-related (adjHR 15.3, 95% CI 10.7-21.8) and noninfection-related cancer (adjHR 2.5, 95% CI 1.5-4.1), as was CD4+ cell count increases less than 100 cells/μl post antiretroviral therapy (ART) (infection-related cancer adjHR 6.6, 95% CI 4.2-10.6, noninfection-related cancer adjHR 2.0, 95% CI 1.2-3.3).Current CD4+ cell count and failure to restore CD4+ cell count both associated with infection and noninfection-related cancer. Viral suppression associated with lower risk of infection-related cancer. Early HIV detection and early adherent ART remain essential for cancer prevention.

Purpose: Recent epidemiological evidence has suggested that use of lipid-lowering medications, particularly statins, was associated with reduced cardiovascular disease (CVD) events and persistent physical disability in healthy older adults. However, the comparative efficacy of different statins in this group remains unclear. This study aimed to compare different forms of statins in their associations with CVD and physical disability in healthy older adults. Methods: This post hoc analysis included data from 5981 participants aged ≥ 70 years (≥ 65 if US minorities; median age:74.0) followed for a median of 4.7 years, who had no prior CVD events or physical disability and reported using a statin at baseline. The incidence of the composite and components of major adverse cardiovascular events and persistent physical disability were compared across different statins according to their type, potency, and lipophilicity using multivariable Cox proportional-hazards models. Results: Atorvastatin was the most used statin type at baseline (37.9%), followed by simvastatin (29.6%), rosuvastatin (25.5%), and other statins (7.0%, predominantly pravastatin). In comparisons of specific statins according to type and lipophilicity (lipophilic vs. hydrophilic statin), observed differences in all outcomes were small and not statistically significant (all p values > 0.05). High-potency statin use (atorvastatin and rosuvastatin) was marginally associated with lower risk of fatal CVD events compared with low-/moderate-potency statin use (hazard ratio: 0.59; 95% confidence interval: 0.35, 1.00). Conclusion: There were minimal differences in CVD outcomes and no significant difference in persistent physical disability between various forms of statins in healthy older adults. Future investigations are needed to confirm our results.

OBJECTIVE This study was undertaken to investigate whether high-sensitivity cardiac troponin T (hs-cTnT) is associated with major adverse cardiovascular events (MACE) in patients with minor stroke or transient ischemic attack (TIA), and whether this association differs after risk stratification based on the Age, Blood Pressure, Clinical Features, Duration of Symptoms, Diabetes (ABCD2 ) score. METHODS INSPiRE-TMS was a randomized controlled trial allocating patients with minor stroke or TIA to an intensified support program or conventional care. In this post hoc analysis, participants were categorized using hs-cTnT levels (5th generation; Roche Diagnostics, Manheim, Germany; 99th percentile upper reference limit [URL] = 14ng/l). Vascular risk was stratified using the ABCD2 score (lower risk = 0-5 vs higher risk = 6-7). Cox proportional hazard regression was performed using covariate adjustment and propensity score matching (PSM) for the association between hs-cTnT and MACE (stroke/nonfatal coronary event/vascular death). RESULTS Among 889 patients (mean age = 70 years, 37% female), MACE occurred in 153 patients (17.2%) during a mean follow-up of 3.2 years. hs-cTnT was associated with MACE (9.3%/yr, >URL vs 4.4%/yr, ≤URL, adjusted hazard ratio [HR] = 1.63 [95% confidence interval (CI) = 1.13-2.35], adjusted HR [Q4 vs Q1 ] = 2.57 [95% CI = 1.35-4.97], adjusted HR [log-transformed] = 2.31 [95% CI = 1.37-3.89]). This association remained after PSM (adjusted HR = 1.76 [95% CI = 1.14-2.72]). There was a significant interaction between hs-cTnT and ABCD2 category for MACE occurrence (pinteraction = 0.04). In the lower risk category, MACE rate was 9.5%/yr in patients with hs-cTnT > URL, which was higher than in those ≤URL (3.8%/yr) and similar to the overall rate in the higher risk category. INTERPRETATION hs-cTnT levels are associated with incident MACE within 3 years after minor stroke or TIA and may help to identify high-risk individuals otherwise deemed at lower risk based on the ABCD2 score. If confirmed in independent validation studies, this might warrant intensified secondary prevention measures and cardiac diagnostics in stroke patients with elevated hs-cTnT. ANN NEUROL 2021;90:901-912.

Background: Risk of relapse within the first months after alcohol use disorder (AUD) interventions is substantial among older adults. For this vulnerable group, little information exists on how this risk is associated with residual DSM-5 AUD symptoms after treatment. Aims: To investigate among older adults who received short-term treatment for DSM-5 AUD (1) the prediction of drinking behaviors and quality of life 12 months after treatment initiation by 6-month DSM-5 AUD symptoms, AUD severity, and AUD remission, and (2) whether these DSM-5 AUD indicators provide prognostic information beyond that gained from 6-month alcohol use (AU) status. Methods: The international multicenter RCT “ELDERLY-Study” enrolled adults aged 60+ with DSM-5 AUD. We used data from the subsample of 323 German and Danish participants with complete DSM-5 AUD criterion information 6 months after treatment initiation (61% male; mean age = 65.5 years). AU was assessed with Form 90, DSM-5 AUD with the M.I.N.I., and quality of life with the WHOQOL-BREF. Generalized linear models were applied to investigate the associations between 6-month AUD indicators and 12-month AU and quality of life. Results: Independent of AU at 6 months, having 1 (vs. no) residual AUD symptom at 6 months predicted a 12-month “slip,” defined as exceeding a blood alcohol concentration of 0.05% at least once during that time (OR: 3.7, 95% CI: 1.5 to 9.0), heavy episodic drinking, and hazardous use (p

In the MYF2001 trial, treatment of Janus kinase (JAK) inhibitor-relapsed/refractory intermediate-2 or high-risk myelofibrosis (MF) with imetelstat 9.4 mg/kg every 3 weeks demonstrated encouraging median overall survival of 29.9 months. To provide historical context, external real-world data (RWD) were collected from a study of 96 patients who had discontinued ruxolitinib and were subsequently treated with best available therapy (BAT) at Moffitt Cancer Center. A closely matched cohort was identified using the MYF2001 eligibility criteria, including patients with MF who had discontinued ruxolitinib due to lack or loss of response. Overall survival was measured from time of JAK inhibitor discontinuation to death or censored at last follow-up. To improve comparability, propensity score weighting approaches using average treatment effect for overlap population (ATO) and stabilized inverse probability treatment weighting (sIPTW) were used for 10 critical baseline covariates. Fifty-seven patients treated with imetelstat 9.4 mg/kg from MYF2001 and 38 patients treated with BAT from RWD were analyzed with improved balanced baseline covariates after propensity score adjustment, showing significantly lower risk of death with imetelstat compared with BAT (hazard ratio: 0.35; p = 0.0019). With sIPTW, results were similar. Results of sensitivity analyses were consistent with the primary analysis. In conclusion, treatment with imetelstat was associated with longer overall survival compared to BAT (30 vs 12 months, respectively) in closely matched patients with MF after JAK inhibitor failure, warranting further evaluation of imetelstat in this poor-prognosis patient population.