PEER simplified lipid guideline 2023 update: Prevention and management of cardiovascular disease in primary care.

OBJECTIVE: To update the 2015 clinical practice guideline and provide a simplified approach to lipid management in the prevention of cardiovascular disease (CVD) for primary care. METHODS: Following the Institute of Medicine's Clinical Practice Guidelines We Can Trust, a multidisciplinary, pan-Canadian guideline panel was formed. This panel was represented by primary care providers, free from conflicts of interest with industry, and included the patient perspective. A separate scientific evidence team performed evidence reviews on statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 inhibitors, fibrates, bile acid sequestrants, niacin, and omega-3 supplements (docosahexaenoic acid with eicosapentaenoic acid [EPA] or EPA ethyl ester alone [icosapent]), as well as on 11 supplemental questions. Recommendations were finalized by the guideline panel through use of the Grading of Recommendations Assessment, Development and Evaluation methodology. RECOMMENDATIONS: All recommendations are presented in a patient-centred manner designed with the needs of family physicians and other primary care providers in mind. Many recommendations are similar to those published in 2015. Statins remain first-line therapy for both primary and secondary CVD prevention, and the Mediterranean diet and physical activity are recommended to reduce cardiovascular risk (primary and secondary prevention). The guideline panel recommended against using lipoprotein a, apolipoprotein B, or coronary artery calcium levels when assessing cardiovascular risk, and recommended against targeting specific lipid levels. The team also reviewed new evidence pertaining to omega-3 fatty acids (including EPA ethyl ester [icosapent]) and proprotein convertase subtilisin-kexin type 9 inhibitors, and outlined when to engage in informed shared decision making with patients on interventions to lower cardiovascular risk. CONCLUSION: These updated evidence-based guidelines provide a simplified approach to lipid management for the prevention and management of CVD. These guidelines were created by and for primary health care professionals and their patients.

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care: PEER umbrella systematic review of systematic reviews.

OBJECTIVE: To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins. DATA SOURCES: MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search. STUDY SELECTION: Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events. SYNTHESIS: A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91). CONCLUSION: Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.

Lignes directrices simplifiées de PEER sur les lipides : actualisation 2023: Prévention et prise en charge des maladies cardiovasculaires en soins primaires.

OBJECTIF: Actualiser le guide de pratique clinique de 2015 et présenter une approche simplifiée de la prise en charge des lipides dans la prévention des maladies cardiovasculaires (MCV) en première ligne. MÉTHODES: Conformément aux recommandations de l'Institute of Medicine dans Clinical Practice Guidelines We Can Trust, un panel pancanadien d'experts multidisciplinaires en lignes directrices a été formé. Ce panel était représentatif des cliniciens en soins primaires, libre de tout conflit d'intérêts avec l'industrie, et il tenait compte des points de vue des patients. Une équipe distincte, responsable des données probantes scientifiques, a passé en revue l'information sur les statines, l'ézétimibe, les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, les fibrates, les chélateurs des acides biliaires, la niacine et les suppléments d'omega-3 (acide docosahexaénoïque avec acide eicosapentaénoïque [EPA] ou ester éthylique de l'EPA seul [icosapent]), ainsi que sur la réponse à 11 questions supplémentaires. Le panel des lignes directrices a finalisé les recommandations en utilisant la méthodologie GRADE (Grading of Recommendations Assessment, Development and Evaluation). RECOMMANDATIONS: Toutes les recommandations sont présentées de manière à être centrées sur le patient et conçues en ayant à l'esprit les besoins des médecins de famille et des autres cliniciens des soins primaires. De nombreuses recommandations sont semblables à celles publiées en 2015. Les statines demeurent le traitement de première intention pour la prévention tant primaire que secondaire des MCV, et le régime méditerranéen et l'activité physique sont recommandés pour réduire le risque cardiovasculaire (en prévention primaire et secondaire). Le panel des lignes directrices a recommandé de ne pas utiliser le dosage des lipoprotéines a, des apolipoprotéines B ou le score calcique coronarien (SCC) dans l'évaluation du risque cardiovasculaire, et de ne pas cibler de seuils précis de taux lipidiques. L'équipe a aussi passé en revue de nouvelles données concernant les acides gras omega-3 (y compris l'ester éthylique d'EAP [icosapent]) et les inhibiteurs de la proprotéine convertase subtilisine-kexine de type 9, et a précisé les moments où il convient de procéder à une prise de décision partagée avec les patients sur les interventions pour diminuer le risque cardiovasculaire. CONCLUSION: Ces lignes directrices actualisées et fondées sur des données probantes présentent une approche simplifiée de la prise en charge des lipides pour la prévention et le traitement des MCV. Ce guide de pratique clinique a été conçu par et pour des professionnels de la santé en soins primaires et leurs patients.

The Effects of Dose, Practice Habits, and Objects of Focus on Digital Meditation Effectiveness and Adherence: Longitudinal Study of 280,000 Digital Meditation Sessions Across 103 Countries.

BACKGROUND: The efficacy of digital meditation is well established. However, the extent to which the benefits remain after 12 weeks in real-world settings remains unknown. Additionally, findings related to dosage and practice habits have been mixed, and the studies were conducted on small and homogeneous samples and used a limited range of analytical procedures and meditation techniques. Findings related to the predictors of adherence are also lacking and may help inform future meditators and meditation programs on how to best structure healthy sustainable practices. OBJECTIVE: This study aimed to measure outcome change across a large and globally diverse population of meditators and meditations in their naturalistic practice environments, assess the dose-response relationships between practice habits and outcome change, and identify predictors of adherence. METHODS: We used ecological momentary assessment to assess participants' well-being over a 14-month period. We engineered outcomes related to the variability of change over time (equanimity) and recovery following a drop in mood (resilience) and established the convergent and divergent validity of these outcomes using a validated scale. Using linear mixed-effects and generalized additive mixed-effects models, we modeled outcome changes and patterns of dose-response across outcomes. We then used logistic regression to study the practice habits of participants in their first 30 sessions to derive odds ratios of long-term adherence. RESULTS: Significant improvements were observed in all outcomes (P<.001). Generalized additive mixed models revealed rapid improvements over the first 50-100 sessions, with further improvements observed until the end of the study period. Outcome change corresponded to 1 extra day of improved mood for every 5 days meditated and half-a-day-faster mood recovery compared with baseline. Overall, consistency of practice was associated with the largest outcome change (4-7 d/wk). No significant differences were observed across session lengths in linear models (mood: P=.19; equanimity: P=.10; resilience: P=.29); however, generalized additive models revealed significant differences over time (P<.001). Longer sessions (21-30 min) were associated with the largest magnitude of change in mood from the 20th session onward and fewer sessions to recovery (increased resilience); midlength sessions (11-20 min) were associated with the largest decreases in recovery; and mood stability was similar across session lengths (equanimity). Completing a greater variety of practice types was associated with significantly greater improvements across all outcomes. Adhering to a long-term practice was best predicted by practice consistency (4-7 d/wk), a morning routine, and maintaining an equal balance between interoceptive and exteroceptive meditations. CONCLUSIONS: Long-term real-world digital meditation practice is effective and associated with improvements in mood, equanimity, and resilience. Practice consistency and variety rather than length best predict improvement. Long-term sustainable practices are best predicted by consistency, a morning routine, and a practice balanced across objects of focus that are internal and external to the body.

Association of MTHFR Polymorphisms With Leukoencephalopathy Risk in Patients With Primary CNS Lymphoma Treated With Methotrexate-Based Regimens.

OBJECTIVES: The folate antagonist high-dose methotrexate (HD-MTX) is integral to induction chemotherapy for primary CNS lymphoma (PCNSL); however, it can be associated with leukoencephalopathy. Methylenetetrahydrofolate reductase (MTHFR) is involved in intracellular folate depletion. We assessed whether MTHFR polymorphisms affect the risk of leukoencephalopathy. METHODS: We retrospectively searched our database at the Massachusetts General Hospital for newly diagnosed PCNSL treated with HD-MTX (without radiotherapy nor intrathecal chemotherapy). RESULTS: Among 68 patients with PCNSL, MTHFR polymorphisms were found in 60 individuals (88.2%) including a 677C→T genotype, a 1298A→C genotype, or a combined 677C→T/1298A→C genotype. Neither MTX clearance nor response to induction therapy was affected by specific genotypes, and complete response was achieved in 72.1% of patients by HD-MTX-based induction. However, the 1298A→C genotype was associated with increased frequency and severity of leukoencephalopathy over time (odds ratio 4.0, CI 1.5-11.4). Such genotype predicted treatment-induced leukoencephalopathy with a sensitivity of 71.0% and a specificity of 62.2% (area under the curve 0.67, CI 0.5-0.8; p = 0.019). While progression-free survival did not differ in genotype-based subgroups, overall survival was lower for the 1298A→C genotype. DISCUSSION: The MTHFR 1298A→C genotype may serve to identify patients with PCNSL at elevated risk of HD-MTX-induced leukoencephalopathy. This seems to translate into reduced survival, potentially due to decreased functional status.

Effect of Mind-Body Skills Training on Quality of Life for Geographically Diverse Adults With Neurofibromatosis: A Fully Remote Randomized Clinical Trial.

Importance: Neurofibromatoses (NF; NF1, NF2, and schwannomatosis) are hereditary tumor predisposition syndromes with a risk for poor quality of life (QOL) and no evidence-based treatments. Objective: To compare a mind-body skills training program, the Relaxation Response Resiliency Program for NF (3RP-NF), with a health education program (Health Enhancement Program for NF; HEP-NF) for improvement of quality of life among adults with NF. Design, Setting, and Participants: This single-blind, remote randomized clinical trial randomly assigned 228 English-speaking adults with NF from around the world on a 1:1 basis, stratified by NF type, between October 1, 2017, and January 31, 2021, with the last follow-up February 28, 2022. Interventions: Eight 90-minute group virtual sessions of 3RP-NF or HEP-NF. Main Outcomes and Measures: Outcomes were collected at baseline, after treatment, and at 6-month and 1-year follow-up. The primary outcomes were physical health and psychological domain scores of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF). Secondary outcomes were the social relationships and environment domain scores of the WHOQOL-BREF. Scores are reported as transformed domain scores (range, 0-100, with higher scores indicating higher QOL). Analysis was performed on an intention-to-treat basis. Results: Of 371 participants who underwent screening, 228 were randomized (mean [SD] age, 42.7 [14.5] years; 170 women [75%]), and 217 attended 6 or more of 8 sessions and provided posttest data. Participants in both programs improved from baseline to after treatment in primary outcomes of physical health QOL score (3RP-NF, 5.1; 95% CI, 3.2-7.0; P < .001; HEP-NF, 6.4; 95% CI, 4.6-8.3; P < .001) and psychological QOL score (3RP-NF, 8.5; 95% CI, 6.4-10.7; P < .001; HEP-NF, 9.2; 95% CI, 7.1-11.2; P < .001). Participants in the 3RP-NF group showed sustained improvements after treatment to 12 months; posttreatment improvements for the HEP-NF group diminished (between-group difference for physical health QOL score, 4.9; 95% CI, 2.1-7.7; P = .001; effect size [ES] = 0.3; and psychological QOL score, 3.7; 95% CI, 0.2-7.6; P = .06; ES = 0.2). Results were similar for secondary outcomes of social relationships and environmental QOL. There were significant between-group differences from baseline to 12 months in favor of the 3RP-NF for physical health QOL score (3.6; 95% CI, 0.5-6.6; P = .02; ES = 0.2), social relationships QOL score (6.9; 95% CI, 1.2-12.7; P = .02; ES = 0.3), and environmental QOL score (3.5; 95% CI, 0.4-6.5; P = .02; ES = 0.2). Conclusions and Relevance: In this randomized clinical trial of 3RP-NF vs HEP-NF, benefits from 3RP-NF and HEP-NF were comparable after treatment, but at 12 months from baseline, 3RP-NF was superior to HEP-NF on all primary and secondary outcomes. Results support the implementation of 3RP-NF in routine care. Trial Registration: ClinicalTrials.gov Identifier: NCT03406208.

A new depsidone from the neotricone-rich chemotype of the lichenised fungus Usnea fulvoreagens.

Individuals of Usnea fulvoreagens (Parmeliaceae, lichenised Ascomycota), a shrubby corticolous species that is widespread in Europe, East Asia and North America, produce medullary lichen acids in several distinct chemotypic patterns. One such chemotype reportedly contains an unidentified substance as the major secondary metabolite. We isolated this compound from Californian specimens of U. fulvoreagens and identified it as the rare depsidone neotricone. A co-occurring compound, conneotricone, was identified as 4,10-dihydroxy-5-(hydroxymethyl)-8-methyl-3,7-dioxo-1,3-dihydro-7H-isobenzofuro[4,5-b][1,4]benzodioxepine-11-carboxylic acid by NMR and HPLC-UV-MSn comparison with the material synthesised from salazinic acid.

Thalamocortical connectivity and its relationship with symptoms and cognition across the psychosis continuum.

BACKGROUND: Coordination between the thalamus and cortex is necessary for efficient processing of sensory information and appears disrupted in schizophrenia. The significance of this disrupted coordination (i.e. thalamocortical dysconnectivity) to the symptoms and cognitive deficits of schizophrenia is unclear. It is also unknown whether similar dysconnectivity is observed in other forms of psychotic psychopathology and associated with familial risk for psychosis. Here we examine the relevance of thalamocortical connectivity to the clinical symptoms and cognition of patients with psychotic psychopathology, their first-degree biological relatives, and a group of healthy controls. METHOD: Patients with a schizophrenia-spectrum diagnosis (N = 100) or bipolar disorder with a history of psychosis (N = 33), their first-degree relatives (N = 73), and a group of healthy controls (N = 43) underwent resting functional MRI in addition to clinical and cognitive assessments as part of the Psychosis Human Connectome Project. A bilateral mediodorsal thalamus seed-based analysis was used to measure thalamocortical connectivity and test for group differences, as well as associations with symptomatology and cognition. RESULTS: Reduced connectivity from mediodorsal thalamus to insular, orbitofrontal, and cerebellar regions was seen in schizophrenia. Across groups, greater symptomatology was related to less thalamocortical connectivity to the left middle frontal gyrus, anterior cingulate, right insula, and cerebellum. Poorer cognition was related to less thalamocortical connectivity to bilateral insula. Analyses revealed similar patterns of dysconnectivity across patient groups and their relatives. CONCLUSIONS: Reduced thalamo-prefrontal-cerebellar and thalamo-insular connectivity may contribute to clinical symptomatology and cognitive deficits in patients with psychosis as well as individuals with familial risk for psychotic psychopathology.

Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report.

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.

A 10-Year Follow-up Survey of Psychiatry Resident Education in Consultation-Liaison Psychiatry.

BACKGROUND: In 2010, the Academy of Consultation-Liaison (then Academy of Psychosomatic Medicine) surveyed US residency programs to understand training in consultation-liaison (CL) psychiatry, leading to recommendations in 2014. Since then, residency training in CL has evolved in the context of competing training demands, increased prioritization of electives, and reactions to coronavirus 2019. OBJECTIVE: To determine the current state of residency training in CL across the United States, including the structure of core and elective resident rotations in CL, attending physician staffing, presence of fellows and other trainees, didactic curriculum, and impact of coronavirus 2019. METHODS: Members of the Academy of Consultation-Liaison Residency Education Subcommittee designed and piloted an 81-question survey tool that was sent to program directors of 269 US general psychiatry training programs for voluntary completion. RESULTS: One hundred three of 269 programs responded to the survey, yielding a response rate of 38.3%. Responding programs were larger and more likely to have a CL fellowship than nonresponding programs. Of the 103 responding programs, 82.5% have more than the minimally required time on CL, with 46.6% reporting an increase in total CL time in the past decade. Since 2010, 18.4% of responding programs changed the placement of the CL rotation, with 43.7% now adherent to the 2014 Academy of Psychosomatic Medicine recommendation to include core CL training in the second half of residency. Thirty-five percent of responding programs require residents to rotate on more than 1 CL service, and 19.4% have a required outpatient CL component. Faculty full-time equivalent varies widely. Of all services included, 33.8% report that all CL faculty are board-certified in CL psychiatry, whereas 18.7% have no board-certified faculty. Of the 103 responding programs, 36.9% offer a CL fellowship, but 31.1% report no residency graduates pursuing CL fellowships in the past 5 years. Of the included programs, 77.7% have a formal CL curriculum for residents, with 34.0% reporting a separate didactic series during the CL rotation. CONCLUSIONS: Among the responding programs, the amount of time spent on core CL rotations has increased in the past decade, but programs have also shifted CL training earlier in the course of residency. Residency programs are increasingly challenged to provide an optimal CL experience, and updated guidance from Academy of Consultation-Liaison may be appreciated.

Leaks From the Tip of the J-pouch: Diagnosis, Management, and Long-term Pouch Survival.

BACKGROUND: The standard of care for surgical treatment of ulcerative colitis is restorative proctocolectomy with ileal J-pouch. Leaks from the tip of the J-pouch are a known complication, but there is a paucity of literature regarding this type of leak. OBJECTIVE: We aimed to describe the diagnosis, management, and long-term clinical outcomes of leaks from the tip of the J-pouch at our institution. DESIGN: This was a retrospective study of a prospectively maintained pouch registry. SETTING: This study was conducted at a quaternary IBD referral center. PATIENTS: Patients included those with ileal J-pouches diagnosed with leaks from the tip of the J-pouch. MAIN OUTCOME MEASURES: The main measures of outcomes were pouch salvage rate, type of salvage procedures, and long-term Kaplan-Meier pouch survival. RESULTS: We identified 74 patients with leaks from the tip of the J-pouch. Pain (68.9%) and pelvic abscess (40.9%) were the most common presentations, whereas 10.8% of patients presented with an acute abdomen. The leak was diagnosed by imaging and/or endoscopy in 74.3% of patients but only discovered during surgical exploration in 25.6% of patients. Some 63.5% of patients were diagnosed only after loop ileostomy closure, whereas 32.4% of patients were diagnosed before ileostomy closure. The most common methods used for diagnosis were pouchoscopy (31.1%) and gastrograffin enema (28.4%). A definitive nonoperative approach was attempted in 48.6% of patients but was successful in only 10.8% of patients overall. Surgical repair was attempted in 89.2% of patients, whereas 4.5% of patients had pouch excision. Salvage operations (n = 63) included sutured or stapled repair of the tip of the J (65%), pouch excision with neo-pouch (25.4%), and pouch disconnection, repair, and reanastomosis (9.5%). Ultimately' 10 patients (13.5%) required pouch excision, yielding an overall 5-year pouch survival rate of 86.3%. LIMITATIONS: This was a retrospective review; referral bias may limit the generalizability. CONCLUSIONS: Leaks from the tip of the J-pouch have variable clinical presentations and require a high index of suspicion. Pouch salvage surgery is required in the majority of patients and is associated with a high pouch salvage rate. See Video Abstract at http://links.lww.com/DCR/C50 . FUGAS DEL EXTREMO DE LA BOLSA EN J DIAGNSTICO, MANEJO Y SUPERVIVENCIA A LARGO PLAZO DE LA BOLSA: ANTECEDENTES:El estándar de atención para el tratamiento quirúrgico de la colitis ulcerosa es la proctocolectomía restauradora con bolsa ileal en J. Las fugas del extremo de la bolsa en J son una complicación conocida, pero hay escasez de literatura sobre este tipo de fuga.OBJETIVO:Describir el diagnóstico, manejo y resultados clínicos a largo plazo de las fugas del extremo de la bolsa en J en nuestra institución.DISEÑO:Estudio retrospectivo de registro de bolsa mantenido prospectivamente.ENTORNO CLINICO:Centro de referencia de enfermedad inflamatoria intestinal cuaternaria.PACIENTES:Pacientes con bolsas ileales en J diagnosticadas con fugas del extremo de la J.PRINCIPALES MEDIDAS DE VALORACIÓN:Tasa de rescate de la bolsa, tipo de procedimientos de rescate y supervivencia a largo plazo de la bolsa Kaplan-Meier.RESULTADOS:Identificamos 74 pacientes con fugas del extremo de la bolsa en J. El dolor (68,9%) y el absceso pélvico (40,9%) fueron las presentaciones más comunes, mientras que el 10,8% de los pacientes presentaron abdomen agudo. La fuga se diagnosticó por imagen y/o endoscopia en el 74,3%, pero solo se descubrió durante la exploración quirúrgica en el 25,6%. El 63,5% fueron diagnosticados solo después del cierre de la ileostomía en asa, mientras que el 32,4% lo fueron antes del cierre de la ileostomía. Los métodos más comunes utilizados para el diagnóstico fueron la endoscopia (31,1%) y el enema de gastrografín (28,4%). Se intentó un abordaje no quirúrgico definitivo en el 48,6%, pero tuvo éxito en solo el 10,8% de los pacientes en general. Se intentó la reparación quirúrgica en el 89,2% de los pacientes, mientras que en el 4,5% se realizó la escisión del reservorio. Las operaciones de rescate (n = 63) incluyeron la reparación con sutura o grapas del extremo de la J (65%), la escisión del reservorio con neo-reservorio (25,4%) y la desconexión, reparación y reanastomosis del reservorio (9,5%). Finalmente, 10 (13,5%) pacientes requirieron la escisión de la bolsa, lo que se asocio con una alta tasa de supervivencia general de la bolsa a los 5 años del 86,3%.LIMITACIONES:Revisión retrospectiva; el sesgo de referencia puede limitar la generalización.CONCLUSIONES:Las fugas del extremo de la bolsa en J tienen presentaciones clínicas variables y requieren un alto índice de sospecha. La cirugía de rescate de la bolsa se requiere en la mayoría y se asocia con una alta tasa de rescate de la bolsa. Consulte Video Resumen en http://links.lww.com/DCR/C50 . (Traducción- Dr. Ingrid Melo ).

Exploring Characteristics of Academic General Surgery Residency Applicants: A Group Concept-Mapping Approach.

OBJECTIVE: Holistic review, which emphasizes qualitative attributes over objective measures, has been proposed as a method for selecting candidates for surgical residency in order to improve diversity in graduate medical education, and, ultimately, the field of surgery. This study seeks to articulate desirable traits of applicants as a first-step in standardizing the holistic review process. DESIGN: Using Group Concept Mapping, a web-based mixed-methods participatory research methodology, residency selection committee members were asked to 1) list desirable characteristics of applicants, 2) group these into categories, 3) rate their importance to academic/clinical success on a 5-point Likert scale (1 = not at all important, 5 = extremely important), and 4) rate the degree to which each characteristic is feasible to assess on a 3-point Likert scale (1 = not at all feasible, 3 = very feasible). Grouped characteristics submitted to hierarchical cluster analysis depicted committee's consensus about desirable qualities/criteria for applicants. Bivariate scatter-plots and pattern-matching graphics demonstrated which of these criteria were most important and reliably assessed. SETTING: A single academic general surgery residency training program in Western Pennsylvania. PARTICIPANTS: Members of the selection committee for the UPMC General Surgery Residency program who had participated in at least 1 prior cycle of applicant selection. RESULTS: Desirable characteristics of highly qualified applicants into an academic general surgery residency were clustered into domains of 1) scholarly work and research, 2) grades/formal assessments, 3) program fit, 4) behavioral assets, and 5) aspiration. Behavioral assets, which was felt to be the most important to clinical and academic success were considered to be the least feasible to reliably assess. Within this domain, initiative, being self-motivated, intellectual curiosity, work ethic, communication skills, maturity and self-awareness, and thoughtfulness were viewed as most frequently reliably assessed from the application and interview process. CONCLUSIONS: High quality applicants possess several behavioral assets that faculty deem are important to academic and clinical success. Adapting validated metrics for assessing these assets, may provide a solution for addressing subjectivity and other challenges scrutinized by critics of holistic review.

Developing a Virtual Equity Hub: Adapting the Tumor Board Model for Equity in Cancer Care.

We define cancer equity as all people having as the same opportunity for cancer prevention, treatment, and survivorship care. However, marginalized populations continue to experience avoidable and unjust disparities in cancer care, access to clinical trials, and cancer survival. Racial and ethnic minorities, and individuals with low socioeconomic status, Medicaid insurance, limited health literacy, disabilities, and mental health disorders are more likely to experience delays to cancer diagnosis and less likely to receive guideline-concordant cancer care. These disparities are impacted by the social determinants of health including structural discrimination, racism, poverty, and inequities in access to healthcare and clinical trials. There is an urgent need to develop and adapt evidence-based interventions in collaboration with community partners that have potential to address the social determinants of health and build capacity for cancer care for underserved populations. We established the Virtual Equity Hub by developing a collaborative network connecting a comprehensive cancer center, academic safety net hospital, and community health centers and affiliates. The Virtual Equity Hub utilizes a virtual tumor board, an evidence-based approach that increases access to multi-specialty cancer care and oncology subspecialty expertise. We adapted the tumor board model by engaging person-centered teams of multi-disciplinary specialists across health systems, addressing the social determinants of health, and applying community-based research principles with a focus on populations with poor cancer survival. The virtual tumor board included monthly videoconferences, case discussion, sharing of expertise, and a focus on addressing barriers to care and trial participation. Specifically, we piloted virtual tumor boards for breast oncology, neuro-oncology, and individuals with cancer and serious mental illness. The Virtual Equity Hub demonstrated promise at building capacity for clinicians to care for patients with complex needs and addressing barriers to care. Research is needed to measure the impact, reach, and sustainability of virtual equity models for patients with cancer.

Restorative proctocolectomy with ileal pouch-anal anastomosis in elderly patients - is advanced age a contraindication?

AIM: We aimed to determine pouch function and retention rate for restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) in elderly patients. METHODS: We identified patients over 50 years old subjected to IPAA for confirmed pathological UC from 1980 until 2016. Patients were grouped according to age: 50-59, 60-69 and 70+ years. Short and long-term outcomes and quality of life (QOL) were compared among the groups. RESULTS: Six hundred and one patients were identified (399 (66.4%) between 50-59 181 (30.1%) between 60-69, and 21 (3.5%) over 70 years of age). More males were in the 70+ arm, and more two-stage procedures were performed in this group. Wound infection increased with age (P = 0.023). There was a trend of more fistula and pouchitis in the 70+ patients (P = 0.052 and P = 0.055, respectively). Pouch failure rate increased with age, and it was statistically significant in the 70+ cohort (P = 0.015). Multivariate stepwise logistic regression showed that pelvic sepsis (HR 4.8 (95% CI 1.5-15.4), P = 0.009), fistula (HR 6.0 (95% CI 1.7-21.5), and mucosectomy with handsewn anastomosis (HR 4.5 (95% CI 1.4-14.7)), were independently associated with pouch failure. No difference was observed in the QOL among the groups, but pouch function was better for patients younger than 60 years. CONCLUSION: In elderly patients with UC, IPAA may be offered with reasonable functional outcomes, and ileal pouch retention rates, as an alternative to the permanent stoma. Stapled anastomosis increases the chance of pouch retention and should be recommended as long as the distal rectum does not carry dysplasia.

Interoception Underlies Therapeutic Effects of Mindfulness Meditation for Posttraumatic Stress Disorder: A Randomized Clinical Trial.

BACKGROUND: Mindfulness-based interventions have proven efficacy in treating posttraumatic stress disorder (PTSD), but the neurobiological mechanism underlying the therapeutic effects is unknown. As mindfulness meditation cultivates attention to the present moment and bodily sensations, neural functions related to interoception (i.e., central processes of bodily signals) might be such a mechanism. METHODS: We conducted a clinical trial in which veterans with PTSD were randomly assigned to receive an 8-week mindfulness-based stress reduction (MBSR) intervention (n = 47) or an active control intervention (present-centered group therapy; n = 51). We assessed pre- and postintervention PTSD symptoms and electroencephalography measures of neural outcomes, including spontaneous brain activity, cognitive task-related brain responses, and interoceptive brain responses (heartbeat-evoked brain responses). We conducted statistical causal mediation analyses using treatment type as a predictor, pre- and postintervention measures of symptom severity as treatment response, and the neural outcomes as mediators. RESULTS: Compared with the control group, the MBSR group had greater improvements in PTSD symptoms and increases in spontaneous alpha power (8-13 Hz), task-related frontal theta power (4-7 Hz in 140-220 ms after stimulus), and frontal theta heartbeat-evoked brain responses (3-5 Hz and 265-336 ms after R peak). The mediation analysis using latent difference score modeling revealed that only changes in frontal theta heartbeat-evoked brain responses mediated the MBSR treatment effect. CONCLUSIONS: Mindfulness meditation improves brain functions of attentional control and resting brain states reflective of internally oriented relaxation. However, interoceptive neural functions enhanced by MBSR seem to be a primary cerebral mechanism that improves symptoms of PTSD.

Clinical Pharmacology of the Dietary Supplement Kratom (Mitragyna speciosa).

Kratom (Mitragyna speciosa) consists of over 40 alkaloids, with 2 of them, mitragynine and 7-OH-mitragynine (7-OH-MG) being the main psychoactive compounds. Mitragynine and 7-OH-mitragynine each target opioid receptors and have been referred to as atypical opioids. They exert their pharmacologic effects on the mu, delta, and kappa opioid receptors. In addition, they affect adrenergic, serotonergic, and dopaminergic pathways. Kratom has been touted as an inexpensive, legal alternative to standard opioid replacement therapy such as methadone and buprenorphine. Other uses for kratom include chronic pain, attaining a "legal high," and numerous central nervous system disorders, including anxiety, depression, and posttraumatic stress disorder. Kratom induces analgesia and mild euphoria, with a lower risk of respiratory depression or adverse central nervous system effects compared to traditional opioid medications. Nonetheless, kratom has been associated with both physical and psychological dependence, with some individuals experiencing classic opioid withdrawal symptoms upon abrupt cessation. Kratom use has been linked to serious adverse effects, including liver toxicity, seizures, and death. These risks are often compounded by polysubstance abuse. Further, kratom may potentiate the toxicity of coadministered medications through modulation of cytochrome P450, P-glycoprotein, and uridine diphosphate glucuronosyltransferase enzymes. In 2016, the US Drug Enforcement Administration took steps to classify kratom as a federal schedule 1 medication; however, due to public resistance, this plan was set aside. Until studies are conducted that define kratom's role in treating opioid withdrawal and/or other central nervous system conditions, kratom will likely remain available as a dietary supplement for the foreseeable future.

Flight training and dietary antioxidants have mixed effects on the oxidative status of multiple tissues in a female migratory songbird.

Birds, like other vertebrates, rely on a robust antioxidant system to protect themselves against oxidative imbalance caused by energy-intensive activities such as flying. Such oxidative challenges may be especially acute for females during spring migration, as they must pay the oxidative costs of flight while preparing for reproduction; however, little previous work has examined how the antioxidant system of female spring migrants responds to dietary antioxidants and the oxidative challenges of regular flying. We fed two diets to female European starlings, one supplemented with a dietary antioxidant and one without, and then flew them daily in a windtunnel for 2 weeks during the autumn and spring migration periods. We measured the activity of enzymatic antioxidants (glutathione peroxidase, superoxide dismutase and catalase), non-enzymatic antioxidant capacity (ORAC) and markers of oxidative damage (protein carbonyls and lipid hydroperoxides) in four tissues: pectoralis, leg muscle, liver and heart. Dietary antioxidants affected enzymatic antioxidant activity and lipid damage in the heart, non-enzymatic antioxidant capacity in the pectoralis, and protein damage in leg muscle. In general, birds not fed the antioxidant supplement appeared to incur increased oxidative damage while upregulating non-enzymatic and enzymatic antioxidant activity, though these effects were strongly tissue specific. We also found trends for diet×training interactions for enzymatic antioxidant activity in the heart and leg muscle. Flight training may condition the antioxidant system of females to dynamically respond to oxidative challenges, and females during spring migration may shift antioxidant allocation to reduce oxidative damage.

HLA-haploidentical vs matched unrelated donor transplants with posttransplant cyclophosphamide-based prophylaxis.

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.