High-normal versus low-normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials.

PURPOSE: Targeted blood pressure thresholds remain unclear in critically ill patients. Two prior systematic reviews have not shown differences in mortality with a high mean arterial pressure (MAP) threshold, but there have been new studies published since. Thus, we conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effect of a high-normal vs low-normal MAP on mortality, favourable neurologic outcome, need for renal replacement therapy, and adverse vasopressor-induced events in critically ill patients. SOURCE: We searched six databases from inception until 1 October 2022 for RCTs of critically ill patients targeted to either a high-normal vs a low-normal MAP threshold for at least 24 hr. We assessed study quality using the revised Cochrane risk-of-bias 2 tool and the risk ratio (RR) was used as the summary measure of association. We used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence. PRINCIPAL FINDINGS: We included eight RCTs with 4,561 patients. Four trials were conducted in patients following out-of-hospital cardiac arrest, two in patients with distributive shock requiring vasopressors, one in patients with septic shock, and one in patients with hepatorenal syndrome. The pooled RRs for mortality (eight RCTs; 4,439 patients) and favourable neurologic outcome (four RCTs; 1,065 patients) were 1.06 (95% confidence interval [CI], 0.99 to 1.14; moderate certainty) and 0.99 (95% CI, 0.90 to 1.08; moderate certainty), respectively. The RR for the need for renal replacement therapy (four RCTs; 4,071 patients) was 0.97 (95% CI, 0.87 to 1.08; moderate certainty). There was no statistical between-study heterogeneity across all outcomes. CONCLUSION: This updated systematic review and meta-analysis of RCTs found no differences in mortality, favourable neurologic outcome, or the need for renal replacement therapy between critically ill patients assigned to a high-normal vs low-normal MAP target. STUDY REGISTRATION: PROSPERO (CRD42022307601); registered 28 February 2022.

RéSUMé: OBJECTIF: Les seuils de pression artérielle ciblés demeurent incertains chez les patient·es gravement malades. Deux revues systématiques antérieures n'ont pas montré de différences dans la mortalité avec un seuil élevé de pression artérielle moyenne (PAM), mais de nouvelles études ont été publiées depuis. Pour cette raison, nous avons réalisé une revue systématique mise à jour et une méta-analyse d'études randomisées contrôlées (ERC) comparant l'effet d'une PAM normale élevée vs normale faible sur la mortalité, les devenirs neurologiques favorables, la nécessité d'un traitement substitutif de l'insuffisance rénale et les événements indésirables induits par les vasopresseurs chez les patient·es gravement malades. SOURCES: Nous avons effectué des recherches dans six bases de données depuis leur création jusqu'au 1er octobre 2022 pour trouver des ERC portant sur des patient·es gravement malades chez lesquel·les un seuil de PAM normale élevée ou normale faible a été ciblé pendant au moins 24 heures. Nous avons évalué la qualité des études à l'aide de l'outil de risque de biais 2 révisé de Cochrane, et le risque relatif (RR) a été utilisé comme mesure sommaire de l'association. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Nous avons inclus huit ERC portant sur 4561 personnes traitées. Quatre études ont été menées chez des patient·es à la suite d'un arrêt cardiaque hors de l'hôpital, deux chez des patient·es présentant un choc distributif nécessitant des vasopresseurs, une chez des patient·es présentant un choc septique et une chez des patient·es atteint·es d'un syndrome hépato-rénal. Les RR combinés pour la mortalité (huit ERC; 4439 personnes) et les devenirs neurologiques favorables (quatre ERC; 1065 personnes) étaient respectivement de 1,06 (intervalle de confiance [IC] à 95 %, 0,99 à 1,14; certitude modérée) et de 0,99 (IC 95 %, 0,90 à 1,08; certitude modérée). Le RR pour le besoin de traitement substitutif de l'insuffisance rénale (quatre ERC; 4071 patient·es) était de 0,97 (IC 95 %, 0,87 à 1,08; certitude modérée). Il n'y avait pas d'hétérogénéité statistique entre les études pour tous les critères d'évaluation. CONCLUSION: Ces revue systématique et méta-analyse mises à jour des ERC n'ont révélé aucune différence dans la mortalité, les devenirs neurologiques favorables ou la nécessité d'un traitement substitutif de l'insuffisance rénale entre les patient·es gravement malades assigné·es à une cible de PAM normale élevée vs normale faible. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022307601); enregistrée le 28 février 2022.

Goal-Directed Care Using Invasive Neuromonitoring Versus Standard of Care After Cardiac Arrest: A Matched Cohort Study.

PURPOSE: Following return of spontaneous circulation after cardiac arrest, hypoxic ischemic brain injury is the primary cause of mortality and disability. Goal-directed care using invasive multimodal neuromonitoring has emerged as a possible resuscitation strategy. We evaluated whether goal-directed care was associated with improved neurologic outcome in hypoxic ischemic brain injury patients after cardiac arrest. DESIGN: Retrospective, single-center, matched observational cohort study. SETTING: Quaternary academic medical center. PATIENTS: Adult patients admitted to the ICU following return of spontaneous circulation postcardiac arrest with clinical evidence of hypoxic ischemic brain injury defined as greater than or equal to 10 minutes of cardiac arrest with an unconfounded postresuscitation Glasgow Coma Scale of less than or equal to 8. INTERVENTIONS: We compared patients who underwent goal-directed care using invasive neuromonitoring with those treated with standard of care (using both total and matched groups). MEASUREMENTS AND MAIN RESULTS: Goal-directed care patients were matched 1:1 to standard of care patients using propensity scores and exact matching. The primary outcome was a 6-month favorable neurologic outcome (Cerebral Performance Category of 1 or 2). We included 65 patients, of whom 21 received goal-directed care and 44 patients received standard of care. The median age was 50 (interquartile range, 35-61), 48 (74%) were male, and seven (11%) had shockable rhythms. Favorable neurologic outcome at 6 months was significantly greater in the goal-directed care group (n = 9/21 [43%]) compared with the matched (n = 2/21 [10%], p = 0.016) and total (n = 8/44 [18%], p = 0.034) standard of care groups. Goal-directed care group patients had higher mean arterial pressure (p < 0.001 vs total; p = 0.0060 vs matched) and lower temperature (p = 0.007 vs total; p = 0.041 vs matched). CONCLUSIONS: In this preliminary study of patients with hypoxic ischemic brain injury postcardiac arrest, goal-directed care guided by invasive neuromonitoring was associated with a 6-month favorable neurologic outcome (Cerebral Performance Category 1 or 2) versus standard of care. Significant work is required to confirm this finding in a prospectively designed study.

Determining Optimal Mean Arterial Pressure After Cardiac Arrest: A Systematic Review.

The use of cerebral autoregulation monitoring to identify patient-specific optimal mean arterial pressure (MAPOPT) has emerged as a technique to augment cerebral oxygen delivery in post-cardiac arrest patients. Our systematic review aims to determine (a) the average MAPOPT in these patients, (b) the feasibility of identifying MAPOPT, (c) the brain tissue oxygenation levels when MAP is within proximity to the MAPOPT and (d) the relationship between neurological outcome and MAPOPT-targeted resuscitation strategies. We carried out this review in accordance with the PRISMA guidelines. We included all studies that used cerebral autoregulation to determine MAPOPT in adult patients (> 16 years old) who achieved return of spontaneous circulation (ROSC) following cardiac arrest. All studies had to include our primary outcome of MAPOPT. We excluded studies where the patients had any history of traumatic brain injury, ischemic stroke or intracranial hemorrhage. We identified six studies with 181 patients. There was wide variability in cerebral autoregulation monitoring methods, length of monitoring, calculation and reporting of MAPOPT. Amongst all studies, the median or mean MAPOPT was consistently above 65 mmHg (range 70-114 mmHg). Definitions of feasibility varied among studies and were difficult to summarize. Only one study noted that brain tissue oxygenation increased as patients' MAP approached MAPOPT. There was no consistent association between targeting MAPOPT and improved neurological outcome. There is considerable heterogeneity in MAPOPT due to differences in monitoring methods of autoregulation. Further research is needed to assess the clinical utility of MAPOPT-guided strategies on decreasing secondary injury and improving neurological outcomes after ROSC.

Fibroid Surgery and Long-Term Improvement in Bladder Symptoms.

OBJECTIVE: Short-term studies have demonstrated improvement in urinary symptoms after fibroid debulking surgery, yet long-term data are lacking. This study assessed the long-term impact of fibroid debulking on urinary symptoms several years postoperatively. METHODS: This case series prospectively investigated changes in urinary symptoms of women who underwent fibroid debulking surgery by several gynaecological surgeons at one centre (2011-2016). A follow-up demographics questionnaire and the Urinary Distress Inventory (UDI) were administered. Changes in total UDI scores and UDI subscale scores from preoperative baseline to long-term follow-up were calculated. RESULTS: Thirty participants were recruited from the original cohort of 61 women (49% long-term follow-up). There were significant improvements in total UDI scores (P < 0.001), obstructive subscale score (P < 0.001), and irritative subscale score (P < 0.001) 2-7 years postoperatively. Stress subscale scores were not significantly improved even in a subgroup of patients with significant baseline bother (P = 0.101). Six of eight women (75%) were cured of bothersome urge urinary incontinence, and three of eight women (37.5%) were cured of bothersome stress urinary incontinence. Baseline fibroid characteristics or type of surgery did not significantly influence outcomes. There were no significant demographic differences between women with sustained improvements and women with no improvement or worsening symptoms. The results are considered Level III evidence as per the Canadian Task Force on Preventive Health Care Levels of Evidence. CONCLUSION: Surgical fibroid removal produces long-term improvement in most bladder symptoms except for stress-related symptoms that persist over time. Women with bothersome urinary symptoms should be investigated for fibroids and counselled on potential long-term benefits of debulking surgery.

Link between Endometriosis, Atherosclerotic Cardiovascular Disease, and the Health of Women Midlife.

Endometriosis and atherosclerotic cardiovascular disease (ASCVD) are both essentially diseases of inflammation. It is well established that inflammation is the leading mechanism in the initiation and maintenance of vascular injury and in the development and progression of atherosclerosis. Thus, if women with endometriosis do indeed have increased general inflammation, they are at increased risk of developing microvascular dysfunction and atherosclerosis. Currently available evidence suggests that young female patients with proven endometriosis may be at a higher lifetime risk of developing cardiovascular disease; this may be unrecognized due to the relatively young age of women found to have endometriosis. Other mechanisms proposed to explain the link between endometriosis and ASCVD include similarities in the genetic underpinnings of each condition, including microRNA dysfunction and the association between endometriosis and early menopause, a risk for developing ASCVD. Although physicians today primarily focus on traditional risk factors when evaluating an individual female patient's risk of developing ASCVD, we believe that a history of endometriosis should be included as a possible risk factor and needs further exploration. A better understanding of the mechanisms linking endometriosis with ASCVD will hopefully guide the implementation of new therapies to mitigate the increased cardiovascular disease burden that patients with endometriosis might face.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

BACKGROUND: Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. STUDY DESIGN AND METHODS: The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. RESULTS: To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. CONCLUSION: The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world.

Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers: A Systematic Review and Meta-analysis.

IMPORTANCE: Brain injury biomarkers released into circulation from the injured neurovascular unit are important prognostic tools in patients with cardiac arrest who develop hypoxic ischemic brain injury (HIBI) after return of spontaneous circulation (ROSC). OBJECTIVE: To assess the neuroprognostic utility of bloodborne brain injury biomarkers in patients with cardiac arrest with HIBI. DATA SOURCES: Studies in electronic databases from inception to September 15, 2021. These databases included MEDLINE, Embase, Evidence-Based Medicine Reviews, CINAHL, Cochrane Database of Systematic Reviews, and the World Health Organization Global Health Library. STUDY SELECTION: Articles included in this systmatic review and meta-analysis were independently assessed by 2 reviewers. We included studies that investigated neuron-specific enolase, S100 calcium-binding protein ß, glial fibrillary acidic protein, neurofilament light, tau, or ubiquitin carboxyl hydrolase L1 in patients with cardiac arrest aged 18 years and older for neurologic prognostication. We excluded studies that did not (1) dichotomize neurologic outcome as favorable vs unfavorable, (2) specify the timing of blood sampling or outcome determination, or (3) report diagnostic test accuracy or biomarker concentration. DATA EXTRACTION AND SYNTHESIS: Data on the study design, inclusion and exclusion criteria, brain biomarkers levels, diagnostic test accuracy, and neurologic outcome were recorded. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. MAIN OUTCOMES AND MEASURES: Summary receiver operating characteristic curve analysis was used to calculate the area under the curve, sensitivity, specificity, and optimal thresholds for each biomarker. Risk of bias and concerns of applicability were assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. RESULTS: We identified 2953 studies, of which 86 studies with 10 567 patients (7777 men [73.6] and 2790 women [26.4]; pooled mean [SD] age, 62.8 [10.2] years) were included. Biomarker analysis at 48 hours after ROSC demonstrated that neurofilament light had the highest predictive value for unfavorable neurologic outcome, with an area under the curve of 0.92 (95% CI, 0.84-0.97). Subgroup analyses of patients treated with targeted temperature management and those who specifically had an out-of-hospital cardiac arrest showed similar results (targeted temperature management, 0.92 [95% CI, 0.86-0.95] and out-of-hospital cardiac arrest, 0.93 [95% CI, 0.86-0.97]). CONCLUSIONS AND RELEVANCE: Neurofilament light, which reflects white matter damage and axonal injury, yielded the highest accuracy in predicting neurologic outcome in patients with HIBI at 48 hours after ROSC. TRIAL REGISTRATION: PROSPERO Identifier: CRD42020157366.

The Impact of Noncavity-Distorting Intramural Fibroids on Live Birth Rate in In Vitro Fertilization Cycles: A Systematic Review and Meta-Analysis.

What is the impact of noncavity-distorting intramural fibroids on live birth rates in in vitro fertilization (IVF) cycles? We searched Embase, MEDLINE, Google Scholar, Cochrane Library, and PUBMED from inception to May 2018. We included studies with women undergoing IVF treatment who had at least one noncavity-distorting intramural fibroid. The studies had to report one or more of the following outcomes: live birth rate as our primary outcome, and implantation rate, clinical pregnancy rate, or miscarriage rate as our secondary outcomes. We excluded studies where women also had submucosal fibroids or had undergone myomectomy. Two authors independently selected studies and extracted data. Methodological quality was assessed using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We included 15 studies with 5029 patients. Patients with noncavity-distorting intramural fibroids had 44% lower odds of live birth (estimated average odds ratio [OR] = 0.56, 95% confidence interval [CI] = 0.46-0.69) and 32% lower odds of clinical pregnancy (estimated average OR = 0.68, 95% CI = 0.56-0.83). Subgroup analysis of women with purely intramural fibroids showed significantly lower odds of live birth rates and clinic pregnancy rates. Analysis of prospective and retrospective studies shows that noncavity-distorting intramural fibroids have a significant adverse effect on live birth rates in women undergoing IVF. Further, well-designed prospective studies are needed to investigate whether removal of these fibroids improves IVF outcomes in this population.

Tibial Sesamoid Position Influence on Functional Outcome and Satisfaction After Hallux Valgus Surgery.

BACKGROUND: During hallux valgus surgery, the abnormal position of the first metatarsal bone relative to the sesamoids is addressed. Our study aimed to investigate the influence of postoperative tibial sesamoid position (TSP) on functional outcome and patient satisfaction after hallux valgus surgery. METHODS: Between February 2007 and November 2011, 250 patients who underwent hallux valgus surgery at our tertiary hospital were followed for 2 years after surgery. They were categorized into 2 groups based on Hardy and Clapham's TSP classification, recorded on postoperative weight-bearing anteroposterior (AP) radiographs: (1) normal (grades I-IV) and (2) outliers (grades V-VII). RESULTS: The mode TSP improved from grade VII preoperatively to grade IV postoperatively (P < .001). The visual analog scale for pain was 1 (95% CI 0, 1) point better in the normal group compared to the outlier group at 2 years after surgery (P = .050), whereas the American Orthopaedic Foot & Ankle Society Hallux Metatarsophalangeal-Interphalangeal Scale was 6 (95% CI 2, 11) points higher in the normal group (P = .009). Patients in the outlier group were also more likely to be dissatisfied with the surgery performed when compared to the normal group (OR 3.881, 95% CI 1.689, 8.920, P = .001). CONCLUSION: We recommend correcting the TSP to grade of IV or less to improve functional outcome and satisfaction after hallux valgus surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative series.

Effect of Obesity on Outcome of Hallux Valgus Surgery.

BACKGROUND: Obesity is a global epidemic, but its effect on foot and ankle surgeries is not well defined. This study aimed to investigate the influence of obesity on functional outcome scores, incidence of postoperative surgical site infection (SSI), and repeat surgery after hallux valgus (HV) corrective surgery. METHODS: Between January 2007 and December 2011, 452 patients who underwent HV corrective surgery at a tertiary hospital were evaluated. They were categorized into 2 groups based on their body mass index (BMI): (1) BMI less than 30 kg/m(2) (control); (2) BMI 30 kg/m(2) or more (obese). The patients were prospectively followed for 2 years. RESULTS: Patients in the obese group were significantly older by 4 years (95% CI, 1-7 years) (P = .043). The preoperative American Orthopaedic Foot & Ankle Society Hallux Metatarsophalangeal-Interphalangeal (AOFAS Hallux MTP-IP) Scale and Physical Component Score were 6 points (95% CI, 1-11 points) and 3 points (95% CI, 1-6 points) poorer, respectively, in the obese group (P = .014 and P = .032, respectively). However, the Visual Analog Scale, AOFAS Hallux MTP-IP Scale, Physical Component Score, and Mental Component Score were comparable between the 2 groups at 6 months and 2 years of follow-up (all P > .05). Eleven patients (3%) in the control group and 1 patient in the obese group (2%) developed postoperative SSI (P = .777). Nine patients (2%) in the control group and 7 patients in the obese group (14%) required repeat surgery for complications (P < .001). CONCLUSION: The authors conclude that while it is important to warn obese patients of the significantly higher risk of repeat surgery, these patients should not be excluded from undergoing HV surgery. LEVEL OF EVIDENCE: Level III, retrospective comparative series.