Influence of lateralized versus medialized reverse shoulder arthroplasty design on external and internal rotation: a systematic review and meta-analysis.

BACKGROUND: Restoration of external (ER) and internal rotation (IR) after Grammont-style reverse shoulder arthroplasty (RSA) is often unreliable. The purpose of this systematic review was to evaluate the influence of RSA medio-lateral offset and subscapularis repair on axial rotation after RSA. METHODS: We conducted a systematic review of studies evaluating axial rotation (ER, IR, or both) after RSA with a defined implant design. Medio-lateral implant classification was adopted from Werthel et al. Meta-analysis was conducted using a random-effects model. RESULTS: Thirty-two studies reporting 2,233 RSAs were included (mean patient age, 72.5 years; follow-up, 43 months; 64% female). The subscapularis was repaired in 91% (n=2,032) of shoulders and did not differ based on global implant lateralization (91% for both, P=0.602). On meta-analysis, globally lateralized implants achieved greater postoperative ER (40° [36°-44°] vs. 27° [22°-32°], P<0.001) and postoperative improvement in ER (20° [15°-26°] vs. 10° [5°-15°], P<0.001). Lateralized implants with subscapularis repair or medialized implants without subscapularis repair had significantly greater postoperative ER and postoperative improvement in ER compared to globally medialized implants with subscapularis repair (P<0.001 for both). Mean postoperative IR was reported in 56% (n=18) of studies and achieved the minimum necessary IR in 51% of lateralized (n=325, 5 cohorts) versus 36% (n=177, 5 cohorts) of medialized implants. CONCLUSIONS: Lateralized RSA produces superior axial rotation compared to medialized RSA. Lateralized RSA with subscapularis repair and medialized RSA without subscapularis repair provide greater axial rotation compared to medialized RSA with subscapularis repair. Level of evidence: 2A.

Meningomyelocele Reconstruction: Comparison of Repair Methods via Systematic Review.

PURPOSE: The purpose of this article was to appraise the various methods of reconstruction for meningomyelocele (MMC) defects. METHODS: A systematic review of the literature was performed to evaluate all reconstructions for MMC. The method of reconstruction was categorized by: primary closure with and without fascial flaps, random pattern flaps, VY advancement flaps (VY), perforator flaps, and myocutaneous flaps. Perforator flaps were subsequently subcategorized based on the type of flap. RESULTS: Upon systematic review, 567 articles were screened with 104 articles assessed for eligibility. Twenty-nine articles were further reviewed and included for qualitative synthesis. Two hundred seventy patients underwent MMC repair. The lowest rates of major wound complications (MWC) were associated with myocutaneous and random pattern flaps. A majority of MWC was in the lumbrosacral/sacral region (87.5% of MWC). In this region, random patterns and perforator flaps demonstrated the lowest rate of MWC (4.5, 8.1%). CONCLUSIONS: Plastic surgery consultation should be strongly considered for MMC with defects in the lumbosacral/sacral region. Perforator flaps are excellent options for the reconstruction of these defects.

Outcome of Patients With Early-Stage Mismatch Repair Deficient Colorectal Cancer Receiving Neoadjuvant Immunotherapy: A Systematic Review.

PURPOSE: We conducted a systematic review to evaluate the outcome of patients with early-stage (stages I-III) mismatch repair deficient (dMMR) colorectal cancer (CRC) receiving neoadjuvant immunotherapy (NIT) with immune checkpoint inhibitor (ICI)-based regimens. METHODS: MEDLINE, Scopus, Embase, Web of Science, and Cochrane Central Register of Controlled Trials were searched for publications reporting the outcome of patients with early-stage dMMR CRC receiving NIT. The primary outcome measures were the complete response (CR) rate (clinical CR [cCR] or pathologic CR [pCR]) and the incidence of grade 3 or higher toxicities. RESULTS: The search identified 37 publications that included 423 patients with colon (n = 326, 77%) and rectal (n = 97,23%) cancers aged 19-82 years; most patients had stage III CRC (88%). Approximately 67% of patients received monotherapy with anti-PD-1 agents; the rest received dual ICIs (ipilimumab plus nivolumab). The CR rate (pCR + cCR) in the overall population was 72% (305 of 423). The R0 resection and pCR rates were 99.3% and 70% among the patients undergoing surgery, respectively. Only four (0.9%) patients had primary resistance to NIT. After median follow-up periods ranging from 4 to 27 months, 3 (0.7%) patients progressed after an initial response. Grade 3 or higher toxicities were uncommon (6.3%), rarely delaying planned surgery. CONCLUSION: NIT in patients with early-stage dMMR CRC is associated with a high response rate, low primary resistance to immunotherapy and cancer recurrence rate, and an excellent safety profile. The findings of the present systematic review support further investigation of NIT in patients with early-stage dMMR CRC, with a particular emphasis on the organ-preserving potential of this strategy.

Gender bias in medical education: A scoping review.

PURPOSE: This scoping review summarises five decades of research on gender bias in subjective performance evaluations of medical trainees. METHOD: A medical librarian searched PubMed, Ovid Embase, Scopus, Web of Science and Cochrane DBSR in June 2020. Two researchers independently reviewed each abstract to determine if it met inclusion criteria (original research article investigating gender bias in subjective medical trainee evaluations by staff). References from selected articles were also reviewed for inclusion. Data were extracted from the articles, and summary statistics were performed. RESULTS: A total of 212 abstracts were reviewed, and 32 met criteria. Twenty (62.5%) evaluated residents, and 12 (37.5%) studied medical students. The majority of studies on residents were Internal Medicine (n = 8, 40.0%) and Surgery (n = 7, 35.0%). All studies were performed in North America and were either retrospective or observational. Nine (28.0%) were qualitative, and 24 (75.0%) were quantitative. The majority of studies were published in the last decade (n = 21, 65.6%). Twenty (62.5%) studies documented gender bias, of which 11 (55%) found that males received higher quantitative performance evaluations and 5 (25%) found that females received higher evaluation scores. The remaining 4 (20%) reported gender differences in qualitative evaluations. CONCLUSIONS: Most studies detected gender bias in subjective performance evaluations of medical trainees, with a majority favouring males. There is a paucity of studies on bias in medical education with a lack of standardised approach to investigating bias.

Community engagement strategies to promote recruitment and participation in clinical research among rural communities: A narrative review.

Residents of rural areas are underrepresented in research. The aim of this narrative review was to explore studies describing the effectiveness of community engagement strategies with rural communities to promote participant recruitment and participation in clinical research. Following PRISMA guidelines, this narrative review was conducted in June 2020. Our search strategy was built around keywords that included community-engaged research, rural community, and recruitment strategies into clinical research. Content-related descriptive statistics were summarized. The selected articles were distributed into categories of levels of community engagement: inform, consult, involve, collaborate, or co-lead. The search resulted in 2,473 identified studies of which forty-eight met inclusion criteria. Of these, 47.1% were randomized controlled trials. The most common levels of engagement were consultation (n = 24 studies) and collaboration (n = 15), while very few focused on informing (n = 2) and co-leadership (n = 2). Strategies, limitations, and findings are discussed for each level of community engagement. This narrative addressed a gap in knowledge regarding participant recruitment in rural communities in relation to assistance from community members. Community engagement contributed to the success of the research, especially in recruitment, participation, and building trust and partnership.

Safety and efficacy of balloon angioplasty compared to stent-based-strategies with pulmonary vein stenosis: A systematic review and meta-analysis.

BACKGROUND: Pulmonary vein stenosis (PVS) is an uncommon but known cause of morbidity and mortality in adults and children and can be managed with percutaneous re-vascularization strategies of pulmonary vein balloon angioplasty (PBA) or pulmonary vein stent implantation (PSI). AIM: To study the safety and efficacy outcomes of PBA vs PSI in all patient categories with PVS. METHODS: We performed a literature search of all studies comparing outcomes of patients evaluated by PBA vs PSI for PVS. We selected all published studies comparing PBA vs PSI for PVS with reported outcomes of restenosis and procedure-related complications in all patient categories. In adults, PVS following atrial fibrillation ablation and in children PVS related to congenital etiology or post-procedural PVS following total or partial anomalous pulmonary venous return repair were included. The patient-centered outcomes were risk of restenosis requiring re-intervention and procedural-related complications. The meta-analysis was performed by computing odds ratios (ORs) using the random effects model based on underlying statistical heterogeneity. RESULTS: Eight observational studies treating 768 severe PVS in 487 patients met our inclusion criteria. The age range of patients was 6 months to 70 years and 67% were males. The primary outcome of the re-stenosis requiring re-intervention occurred in 196 of 325 veins in the PBA group and 111 of 443 veins in the PSI group. Compared to PSI, PBA was associated with a significantly increased risk of re-stenosis (OR 2.91, 95%CI: 1.15-7.37, P = 0.025, I 2 = 79.2%). Secondary outcomes of the procedure-related complications occurred in 7 of 122 patients in the PBA group and 6 of 69 in the PSI group. There were no statistically significant differences in the safety outcomes between the two groups (OR: 0.94, 95%CI: 0.23-3.76, P = 0.929), I 2 = 0.0%). CONCLUSION: Across all patient categories with PVS, PSI is associated with reduced risk of re-intervention and is as safe as PBA and should be considered first-line therapy for PVS.

The Role of Systemic Therapy in Resectable Colorectal Liver Metastases: Systematic Review and Network Meta-Analysis.

BACKGROUND: Despite multiple randomized trials, the role of perioperative chemotherapy in colorectal cancer liver metastasis (CRLM) is still under debate. In this systematic review and network meta-analysis (NMA), we aim to evaluate the efficacy of perioperative systemic therapies for patients with CRLM. METHODS: We searched various databases for abstracts and full-text articles published from database inception through May 2021.We included randomized controlled trials (RCTs) comparing the addition of perioperative (post, pre, or both) systemic therapies to surgery alone in patients with CRLM. The outcomes were compared according to the chemotherapy regimen using a random effects model. Outcomes of interest included disease-free survival (DFS) and overall survival (OS). RESULTS: Seven RCTs with a total of 1504 patients with CRLM were included. Six studies included post-operative treatment and one evaluated perioperative (pre- and postoperative) therapy. Fluoropyrimidine-based chemotherapy was the most used systemic therapy. NMA showed benefit of adding perioperative therapy to surgery in terms of DFS (HR 0.73, 95% CI 0.63 to 0.84). However, these findings did not translate into a statistically significant OS benefit (HR 0.88, 95% CI 0.74 to 1.05). NMA did not show any advantage of one regimen over another including oxaliplatin or irinotecan. CONCLUSIONS: This systematic review and NMA of 7 RCTs found that the addition of perioperative systemic treatment for resectable CRLM could improve disease-free survival but not overall survival. Based on the findings, addition of perioperative treatment in resectable CRLM should be individualized weighing the risks and benefits.

Representation of Women on Plastic Surgery Journal Editorial Boards in the United States.

BACKGROUND: During the past decade, a growing number of women have pursued medical careers, including in plastic surgery. However, female physicians have tended to be underrepresented in a variety of leadership roles in their respective specialties. OBJECTIVES: The authors sought to evaluate the representation of female plastic surgeons on the editorial boards of high-impact plastic surgery journals. METHODS: The gender of editorial board members on 3 high-impact plastic surgery journals was evaluated from 2009 and 2018. The number of women on each editorial board was then compared with the number of board-certified female plastic surgeons (BCFPS) and board-certified female academic plastic surgeons (BCFAPS), a subgroup of BCFPS. RESULTS: There were 555 unique editorial board members from Plastic and Reconstructive Surgery, Aesthetic Surgery Journal, and Annals of Plastic Surgery from 2009 to 2018. During that period, 72 editors (13.0%) were women. At the beginning of the study, there were significantly fewer female editors than expected based on proportionate representation of BCFPS and BCFAPS to all board-certified plastic surgeons (P = 0.007 and 0.007, respectively). During the study, there was a 177% increase in women holding editorial board positions. At study end, women were adequately represented on all 3 editorial boards compared with their population data (BCFPS and BCFAPS). CONCLUSIONS: During the 10 years of this study (2009-2018), editorial boards have overcome the underrepresentation of women on, and female plastic surgeons are currently adequately represented on the top 3 high-impact journal editorial boards.

Systemic Therapy and Sequencing Options in Advanced Hepatocellular Carcinoma: A Systematic Review and Network Meta-analysis.

Importance: The treatment landscape for advanced hepatocellular carcinoma (HCC) has recently changed and become relatively confusing. Head-to-head comparisons between most of the available agents have not been performed and are less likely to be examined in a prospective fashion in the future. Therefore, a network meta-analysis (NMA) is helpful to compare different agents from across different trials. Objective: To evaluate comparative effectiveness of different systemic treatments in advanced patients with HCC across lines of therapy. Data Sources: We searched various databases for abstracts and full-text articles published from database inception through March 2020. Study Selection: We included phase 3 trials evaluating different vascular endothelial growth factor inhibitors (VEGFis), checkpoint inhibitors (CPIs), or their combinations in advanced HCC, in the first-line or refractory setting. Data Extraction and Synthesis: The reporting of this systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The overall effect was pooled using the random effects model. Main Outcomes and Measures: Outcomes of interest included overall (OS) and progression-free survival (PFS). Findings: Fourteen trials (8 in the first-line setting and 6 in the second-line setting) at low risk of bias were included. The 8 trials in the first-line setting encompassed a total of 6290 patients, with an age range of 18 to 89 years. The 5 trials included in the second-line analysis encompassed a total of 2653 patients, with an age range of 18 to 91 years. Network meta-analysis showed the combination of atezolizumab and bevacizumab was superior in patients with HCC treated in the first-line setting compared with lenvatinib (HR, 0.63; 95% CI, 0.44-0.89), sorafenib (HR, 0.58; 95% CI, 0.42-0.80), and nivolumab (HR, 0.68; 95% CI, 0.48-0.98). In the refractory setting, NMA showed that all studied drugs had PFS benefit compared with placebo. However, this only translated into OS benefit with regorafenib (HR, 0.62; 95% CI, 0.51-0.75) and cabozantinib (HR, 0.76; 95% CI, 0.63-0.92) compared with placebo. In the NMA of patients with α-fetoprotein (AFP) levels of 400 ng/mL or greater, regorafenib, cabozantinib, and ramucirumab showed PFS and OS benefit compared with placebo with no superiority of an active drug compared with any others. Conclusions and Relevance: This systematic review and NMA of 14 trials found that atezolizumab and bevacizumab in combination is now considered the standard of care in the first-line setting in patients with advanced HCC. Regorafenib and cabozantinib are preferred options in refractory patients, with ramucirumab as an additional option in those with levels of AFP of 400 ng/mL or higher. Future trials should focus on other potential combinations and best treatment strategy in patients with prior VEGFi/CPI exposure.

Safety and efficacy of direct oral anticoagulants compared to Vitamin K antagonists postpercutaneous coronary interventions in patients with atrial fibrillation: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) are commonly associated. Cotreatment with multiple antithrombotic agents can increase the risk of bleeding. We sought to evaluate patient-centered outcomes in patients with AF on double therapy with direct oral anticoagulants (DOACs) compared to patients with standard triple therapy, [a vitamin K antagonist (VKA) plus dual antiplatelet therapy]. METHODS: We performed a literature search of randomized controlled trials (RCTs) reporting outcomes of patients receiving double therapy with DOACs compared to triple therapy with VKAs in patients with AF undergoing percutaneous coronary intervention (PCI). Patient-centered outcomes were the International Society of Thrombosis and Hemostasis (ISTH) major or clinically relevant nonmajor bleeding (CRNB), all-cause mortality, major adverse cardiovascular events (MACE), stent thrombosis, myocardial infarction, and stroke. RESULTS: Four RCTs (9602 patients) met our inclusion criteria. Compared to VKAs, DOACs were associated with significantly lower ISTH major bleeding/ CRNB (RR: 0.75, 95% CI: 0.67-0.82, P < .00001, I 2 = 11%). There were no statistically significant differences in the efficacy outcomes, including myocardial infarction (RR: 0.99, 95% CI :0.79-1.25, P = .96), stent thrombosis (RR: 0.97, 95% CI: 0.6-1.55, P = .89), ischemic stroke (RR: 0.76, 95% CI: 0.5-1.15, P = .19), all-cause mortality (RR: 1.06, 95% CI: 0.85-1.31, P = .61), and MACE (RR: 1.06, 95% CI: 0.91-1.22, P = .97). CONCLUSION: Compared with triple therapy with VKAS, double therapy with DOACs is associated with a reduced risk of bleeding and is as effective in patients with AF undergoing PCI.

The Role of Maintenance Strategies in Metastatic Colorectal Cancer: A Systematic Review and Network Meta-analysis of Randomized Clinical Trials.

Importance: In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials. Objective: To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer. Evidence Review: MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added. Findings: Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev). Conclusions and Relevance: For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.

Elevating Evidence-Based Practice: A Multi-Site Workshop Pilot for Nurses.

Leveraging an established evidence-based practice (EBP) workshop at the Mayo Clinic campus in Arizona, the manager of Nursing Research asked local library staff to discuss the research process and to demonstrate to the attendees how to use literature databases to support their research projects and EBP practices on their units. The EBP workshop was presented via video conference from the originating location to two remote locations within the organization. Each remote site had a librarian in attendance to support the librarian at the originating campus. This method allowed the librarians at each site to guide and assist patrons and establish a face-to-face connection with attendees.

Efficacy of Pharmacologic and Cardiac Implantable Electronic Device Therapies in Patients With Heart Failure and Reduced Ejection Fraction: A Systematic Review and Network Meta-Analysis.

Background The treatment of heart failure with reduced ejection fraction has been the subject of numerous randomized controlled trials involving medications and cardiac implantable electronic device therapies. As newer effective pharmacological therapies suggest significant reductions in all-cause mortality, the role of additional device therapy in heart failure with reduced ejection fraction deserves further scrutiny. Methods A systematic review and network meta-analysis on the effect of medication and device therapies in heart failure with reduced ejection fraction on all-cause mortality was performed. Randomized controlled trials published between January 1980 and July 2017 were identified using Medline, EMBASE, and Cochrane Controlled Register of Trials databases. Pcnetmeta package in R was used to calculate treatment arm-based estimated rates, rate ratios, and probability ranks with 95% credible intervals. Results Combination therapy of ACE (angiotensin-converting enzyme) inhibitors or ARBs (angiotensin receptor blockers) with ß-blockers (BBs) alone or in addition to implantable cardiac defibrillators or cardiac resynchronization therapy with defibrillators demonstrated a significant reduction of all-cause mortality when compared with placebo. By probability rank, implantable cardiac defibrillator+ACE inhibitor or ARB+BB+mineralocorticoid receptor antagonist, implantable cardiac defibrillator+ACE inhibitor or ARB+BB, and angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist combination therapies have the highest probability of being ranked the best treatment. There was no significant difference in the rate of mortality when comparing angiotensin receptor-neprilysin inhibitor+BB+mineralocorticoid receptor antagonist to implantable cardiac defibrillator+optimal pharmacological combination therapy. Conclusions BB and renin-angiotensin system blockers alone or in combination with defibrillator device therapy have robust evidence for a reduction in mortality compared with placebo. The comparative efficacy of pharmacological therapy with angiotensin receptor-neprilysin inhibitors and device therapy deserves further investigation.

Catheter ablation for treatment of atrial fibrillation in patients with heart failure with reduced ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Atrial fibrillation (AF) among patients with heart failure with reduced ejection fraction (HFrEF) is associated with adverse clinical outcomes. Our primary aim was to evaluate patient-centered outcomes and surrogate outcomes following catheter ablation (CA) of AF among patients with HFrEF compared to standard medical therapy with or without device therapy (atrioventricular node ablation and cardiac resynchronization therapy). METHODS: A systematic literature review was performed limiting our searches to randomized control trials reporting outcomes of CA compared to standard medical therapy with or without device therapy were included. Patient-centered outcomes were relative reduction in all-cause mortality, heart failure readmissions, and recurrence of AF. Surrogate outcomes of interest were change in ejection fraction, change in peak oxygen consumption, reduction in brain natriuretic peptide levels, change in 6-minute walk distance, and change in Minnesota living with heart failure score. RESULTS: Seven randomized control trials (Patient n = 721) met our inclusion criteria. All trials used radiofrequency energy for CA of AF. CA for AF was associated with significantly lower all-cause mortality (Risk ratio [RR] = 0.52, 95% confidence interval [CI] = 0.35-0.76, P = 0.001, I 2 = 0%), lower rate of heart failure readmission (RR = 0.58, 95% CI = 0.46-0.74, P < 0.001, I 2 = 0%) and lower rate of AF recurrence (RR = 0.33, 95% CI = 0.22-0.50, P < 0.001, I 2 = 68%) as compared to standard medical therapy. Surrogate outcomes showed a similar benefit favoring CA. CONCLUSION AND RELEVANCE: Catheter ablation for AF in HFrEF is associated with improvement in patient-centered outcomes and surrogate outcomes when compared to standard medical therapy with or without device therapy.

High-Dose Chemotherapy with Early Autologous Stem Cell Transplantation Compared to Standard Dose Chemotherapy or Delayed Transplantation in Patients with Newly Diagnosed Multiple Myeloma: A Systematic Review and Meta-Analysis.

Autologous stem cell transplantation (SCT) is the standard of care for all transplantation-eligible patients diagnosed with multiple myeloma (MM). Various studies have compared clinical outcomes with frontline SCT ("early SCT") versus standard-dose therapy (SDT) alone, with or without salvage SCT ("SDT/late SCT"). In this meta-analysis, we compare overall survival (OS) and progression-free survival (PFS) outcomes between these 2 treatment approaches. Twelve studies were identified, including a total of 3633 patients, of whom 1811 received early SCT and 1822 received SDT/late SCT. In our analysis of all 12 studies, OS was not significantly different between the 2 groups (hazard ratio [HR], .86; 95% confidence interval [CI], .70 to 1.04), but PFS was better with early SCT (HR, .67; 95% CI, .54 to .82). In a subgroup analysis of 3 studies in which novel agents were used for induction, OS again was similar in the 2 groups, and PFS was favorable with early SCT (HR, .50; 95% CI, .36 to .70). This analysis shows that over the years, early SCT has been associated with prolonged PFS, but this did not consequently translate into prolonged OS in patients with newly diagnosed MM. The benefit of early SCT in terms of OS is less clear in the era of novel agents, given the limited follow-up of these studies.

Choosing a Reduced-Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation, Fludarabine/Busulfan versus Fludarabine Melphalan: A Systematic Review and Meta-Analysis.

Fludarabine with busulfan (FB) or melphalan (FM) are 2 more commonly used reduced-intensity conditioning (RIC) regimens for allogeneic stem cell transplantation (HCT).We present a systematic review and meta-analysis of studies comparing these 2 RIC regimens. We searched electronic databases from inception through November 1, 2017 for literature searches to identify relevant studies. A DerSimonian random effects model was used to measure efficacy outcomes; hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) are reported. Seven studies, including a total of 1955 patients, met criteria for inclusion, of which 6 were included in the overall pooled analysis because of repetition of some patients in 2 studies. Three studies were included in the subgroup analysis of acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) and 2 in the subgroup analysis of lymphoid malignancies. Overall survival (OS) and progression-free survival were not statistically significantly different between the 2 RIC regimens in analysis of all studies. However, OS was better with FM in subgroup analysis of AML/MDS studies (HR, .83; 95% CI, .73 to .95). Nonrelapse mortality was lower with FB (HR, .64; 95% CI, .46 to .89), whereas relapse was lower with FM (HR, 1.52; 95% CI, 1.13 to 2.06) in the analysis of all studies. This meta-analysis shows that FB and FM are associated with a similar OS in patients undergoing HCT. Relapse rates are lower with FM but at the cost of higher nonrelapse mortality.

Does High Cerebral Microbleed Burden Increase the Risk of Intracerebral Hemorrhage After Intravenous Tissue Plasminogen Activator for Acute Ischemic Stroke?

BACKGROUND: The risk of developing intracerebral hemorrhage (ICH) after the administration of intravenous tissue plasminogen activator for acute ischemic stroke is well established in the general population. However, the risk associated with stroke thrombolysis in patients with a history of cerebral microbleeds (CMBs) is undetermined. OBJECTIVE: The main objective of this study was to critically assess current evidence with regard to the risk of development of ICH after the administration of intravenous tissue plasminogen activator for acute ischemic stroke in patients with CMBs. METHODS: The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular and hospital neurology. RESULTS: A recent individual patient data meta-analysis was selected for critical appraisal. Cohorts were analyzed with pretreatment magnetic resonance imaging to determine CMB burden and were followed-up to assess subsequent symptomatic ICH, hemorrhagic transformation, parenchymal hemorrhage (PH), and remote PH (PHr) following intravenous thrombolysis. Risk of symptomatic ICH, PH, and PHr was increased in the presence of CMBs, with PHr having the strongest association with increasing CMB burden. Only patients with >10 CMBs were found to have associations with poor outcome at 3 to 6 months, whereas there was no association with 3 to 6 months' mortality. CONCLUSIONS: CMBs are associated with an increased risk of postthrombolysis ICH; however, the clinical implications have yet to be determined.

Adjuvant Antiangiogenic Agents in Post-nephrectomy Renal Cell Carcinoma: A Systematic Review and Meta-analysis.

CONTEXT: The role of antiangiogenic agents in advanced renal cell carcinoma (RCC) is well established. However, it is still not clear whether this benefit can be extrapolated to the adjuvant setting. OBJECTIVE: To determine the efficacy and safety of antiangiogenic agents in patients with RCC and a high risk of relapse after nephrectomy. EVIDENCE ACQUISITION: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) evaluating the use of any oral antiangiogenic agent compared to placebo in post-nephrectomy RCC patients. Prespecified data elements were extracted from each trial. Outcomes of interest included overall survival (OS) and disease-free survival (DFS). The overall effect was pooled using the DerSimonian and Laird random-effects models. EVIDENCE SYNTHESIS: Three RCTs comparing antiangiogenics to placebo among 3693 patients met our inclusion criteria and were used in meta-analyses. Overall, antiangiogenics did not improve DFS (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.78-1.07) or OS (HR 0.99, 95% CI 0.79-1.25). These results persisted when restricting the analysis to patients with clear cell carcinoma and patients with highest risk of relapse. Similarly, sunitinib did not show any improvement in the entire cohort for either DFS (HR 0.89, 95% CI 0.67-1.19) or OS (HR 1.11, 95% CI 0.90-1.37). CONCLUSIONS: In this meta-analysis, antiangiogenics did not improve OS and DFS over placebo in high-risk RCC after nephrectomy. Further studies are needed to identify the patient population that might derive a benefit from antiangiogenics in the adjuvant setting. PATIENT SUMMARY: In this article, we found that there is currently insufficient evidence to support the use of oral antiangiogenics in nonmetastatic renal cell carcinoma after nephrectomy. In addition, the use of oral antiangiogenics was associated with a 2.7-fold higher rate of significant side effects compared to placebo.