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Background: Long-term posttreatment surveillance imaging algorithms for head and neck squamous cell carcinoma are not standardized due to debates over optimal surveillance strategy and efficacy. Consequently, current guidelines do not provide long-term surveillance imaging recommendations beyond 6 months., Purpose: We performed a systematic review to evaluate the impact of long-term imaging surveillance (ie, imaging beyond 6 months following completion of treatment) on survival in patients treated definitively for head and neck squamous cell carcinoma., Data Sources: A search was conducted on PubMed, EMBASE, Scopus, the Cochrane Central Register of Controlled Trials, and the Web of Science for English literature published between 2003 and 2024 evaluating the impact of long-term surveillance imaging on survival in patients with head and neck squamous cell carcinoma., Study Selection: We screened 718 abstracts and performed full-text review for 95 abstracts, with 2 articles meeting the inclusion criteria. The Risk of Bias in Non-Randomized Studies of Interventions assessment tool was used., Data Analysis: A qualitative assessment without a pooled analysis was performed for the 2 studies meeting inclusion criteria., Data Synthesis: No randomized prospective controlled trials were identified. Two retrospective 2-arm studies were included comparing long-term surveillance imaging with clinical surveillance and were each rated as having a moderate risk of bias. Each study included heterogeneous populations with variable risk profiles and imaging surveillance protocols. Both studies investigated the impact of long-term surveillance imaging on overall survival and came to different conclusions, with 1 study reporting a survival benefit for long-term surveillance imaging with FDG-PET/CT in patients with stage III or IV disease or an oropharyngeal primary tumor and the other study demonstrating no survival benefit., Limitations: Limited heterogeneous retrospective data available precludes definitive conclusions on the impact of long-term surveillance imaging in head and neck squamous cell carcinoma., Conclusions: There is insufficient quality evidence regarding the impact of long-term surveillance imaging on survival in patients treated definitively for head and neck squamous cell carcinoma. There is a lack of a standardized definition of long-term surveillance, variable surveillance protocols, and inconsistencies in results reporting, underscoring the need for a prospective multicenter registry assessing outcomes., (© 2025 by American Journal of Neuroradiology.)

Importance: Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development., Objective: To assess the association between MRD and PFS in CLL using data from prospective clinical trials that studied targeted agents or obinutuzumab-based treatment., Data Sources: Clinical studies on CLL were identified via searches of PubMed, Embase, Scopus, and Web of Science from inception through July 31, 2023., Study Selection: Prospective, single-arm, and randomized clinical trials that assessed targeted agents or obinutuzumab-based treatment and reported PFS by MRD status were included. Studies with insufficient description of MRD information were excluded., Data Extraction and Synthesis: Study sample size, median patient age, median follow-up time, line of treatment, MRD detection method and time points, and survival outcomes were extracted., Main Outcomes and Measures: Analyses of survival probabilities and hazard ratios (HRs) were conducted for PFS according to MRD status. Meta-analyses were performed using a random-effects model., Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40)., Conclusions and Relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.

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.

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., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

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.

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., (© 2023 John Wiley & Sons Ltd and The Association for the Study of Medical Education.)

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., Competing Interests: Conflict-of-interest statement: All the authors received no financial support for the research, authorship, and/or publication of this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: The authors have no conflict of interest to disclose., (© The Author(s) 2023.)

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., (© The Author(s) 2022. Published by Oxford University Press.)

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., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

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.

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.

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., Competing Interests: The authors declare no conflict of interests for this article., (© 2020 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

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.

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 β-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.

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., (Copyright © 2018. Published by Elsevier Inc.)

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., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Authors declare no conflict of interests for this article.

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.

Mantle cell lymphoma is characterized by relapse and progressive disease, despite initial response to chemoimmunotherapy. We conducted a systematic review and meta-analysis to determine the efficacy of rituximab maintenance (RM) therapy in patients with mantle cell lymphoma. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials from database inception through November 1, 2017. Only full-text articles were included. Prespecified data elements were extracted from each trial. Outcomes of interest included progression-free survival (PFS) and overall survival (OS). The overall effect was pooled using the Der Simonian-Laird random effects model. Three randomized controlled trials and four observational studies met our inclusion criteria and were identified in the analyses. Six studies compared RM therapy to observation, and one compared RM therapy to interferon alfa. Meta-analysis evaluating outcomes of patients treated after ASCT revealed that RM improved for both PFS (HR = 0.33, 95% CI = 0.23-0.49) and OS (HR of death = 0.35, 95% CI = 0.17-0.69). A second meta-analysis of studies evaluating outcomes of patients who are ASCT-ineligible treated with anthracycline-based induction therapy revealed that RM improved PFS (HR = 0.38, 95% CI = 0.25-0.58). There is a paucity of data on the role of RM in ASCT-ineligible patients and those with relapsed disease. Overall, RM therapy appears to improve PFS and OS in previously untreated patients with mantle cell lymphoma who undergo induction chemoimmunotherapy followed by ASCT., (© 2018 Wiley Periodicals, Inc.)

Background: To determine the predictive value of retinal microvascular abnormalities for cerebrovascular ischemic diseases (CVDs), we aimed to investigate the quantitative association between retinal microvascular changes and CVD subcategories: white matter hyperintensities (WMHIs), lacunar infarcts (LIs), and cerebral infarctions (CIs)., Methods: Using Meta-analyses Of Observational Studies in Epidemiology guidelines, we searched 6 databases through September 2016 for studies evaluating the linkage between retinal microvascular abnormalities and WMHI, and LI and CI. Studies were included if they reported odds ratios (ORs) and 95% confidence intervals or raw patient level data (that were computed into ORs). Unadjusted and vascular risk-factor adjusted ORs were pooled into meta-analysis using DerSimonian Laird random effects model. Study quality and dissemination biases were assessed and integrated., Results: From 24,444 search-identified records, 28 prospective studies encompassing 56,379 patients were eligible for the meta-analysis. After vascular risk-factor adjustment, focal arteriolar narrowing was associated with WMHI (OR, 1.24 [1.01-1.79]), LI (OR, 1.77 [1.14-2.74]), and CI (OR, 1.75 [1.14-2.69]). Venular dilation was associated with LI (OR, 1.46 [1.10-1.93]), and retinal hemorrhages with WMHI (OR, 2.23 [1.34-3.70]). Any retinopathy exhibited significant association with CI (OR, 1.96 [1.65-2.50]). Heterogeneity was significant (I 2 >50%) for all syntheses except retinal hemorrhages and WMHI, and retinopathy and CI (I 2 =0 ⋅ 0%). Associations remained significant after adjustments for quality and publication bias., Conclusions: We found the most significant association between retinal hemorrhages and WMHI. Focal arteriolar narrowing and retinopathy predicted CVD subtypes after risk-factor adjustment, suggesting that features different than traditional vascular risk factors, are involved in CVD pathophysiology., (Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Financial disclosures: Thai H. Ho certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Thai H. Ho has served on advisory boards for Pfizer, Genentech, and Exelixis. Richard W. Joseph has acted as a consultant for BMS, Exelixis, Novartis, Merck, and Incyte. The remaining authors have nothing to disclose.

Background: Catamenial epilepsy refers to cyclic seizure exacerbation in relation to the menstrual cycle. Three distinct patterns have been described: C1-perimenstrual, C2-periovulatory, and C3-inadequate luteal. There is experimental and clinical evidence that gonadal steroid hormones affect neuronal excitability with estrogens being mainly proconvulsant and progesterone anticonvulsant. If reproductive steroids have a role in seizure occurrence, they may also have a role in treatment., Objective: The objective of this study was to critically assess current evidence regarding the efficacy of progesterone as adjunctive therapy in women with intractable catamenial epilepsy., Methods: The objective was addressed through the development of a structured critically appraised topic. This included a clinical scenario with a clinical question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom line conclusions. Participants included consultant and resident neurologists, medical librarian, and content experts in the fields of epilepsy and gynecology., Results: A randomized, placebo-controlled clinical trial was selected for critical appraisal. This trial compared the efficacy of adjunctive cyclic natural progesterone therapy versus placebo for seizures in women with intractable partial epilepsy, stratified by catamenial and noncatamenial status. There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation is a significant predictor of the responder rate for progesterone therapy., Conclusions: Cyclic natural progesterone is not superior to placebo in reducing seizure frequency in women with intractable partial epilepsy. Posthoc findings suggest that progesterone may benefit a subset of women with perimenstrually exacerbated seizures.

Background: There are limited therapeutic options for treatment-refractory pancreatic ductal adenocarcinoma (PDAC), with a paucity of data to support the best option after progression on gemcitabine-based regimens. The authors performed a meta-analysis to determine the effectiveness of adding oxaliplatin (OX) or various irinotecan formulations to a fluoropyrimidine (FP) after first-line treatment progression in patients with PDAC., Methods: Different databases, including PubMed, EMBASE, and Cochrane, were searched to identify randomized controlled trials comparing FP monotherapy versus FP combination therapy that included either oxaliplatin (FPOX) or various irinotecan formulations (FPIRI) in patients with PDAC who progressed after first-line treatment. Secondary analyses were planned to assess the effectiveness of FPOX and FPIRI compared with FP. Outcomes of interest included overall survival (OS) and progression-free survival (PFS)., Results: Five studies with 895 patients were identified. Patients randomized to receive FPIRI/FPOX had a significantly improved PFS and a trend toward improved OS compared with those who received FP monotherapy. When comparing FPIRI with FP, there was an improvement in both PFS (hazard ratio, 0.64; 95% confidence interval, 0.47-0.87; P = .005) and OS (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004) in patients who received the combination. Conversely, FPOX produced only a modest improvement in PFS with no improvement in OS., Conclusions: Combination chemotherapy with OX or various IRI formulations appears to improve PFS compared with single-agent FP. FPIRI, but not FPOX, appears to confer an OS advantage. The combination of FP with irinotecan formulations appears to be the appropriate next line of treatment upon progression after gemcitabine-based chemotherapy regimens. Cancer 2017;123:4680-4686. © 2017 American Cancer Society., (© 2017 American Cancer Society.)