Maintenance therapy for chronic lymphocytic leukaemia.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is the most common lymphoproliferative disease in adults and currently remains incurable. As the progression-free period shortens after each successive treatment, strategies such as maintenance therapy are needed to improve the degree and duration of response to previous therapies. Monoclonal antibodies, immunomodulatory agents, and targeted therapies are among the available options for maintenance therapy. People with CLL who achieve remission after previous therapy may choose to undergo medical observation or maintenance therapy to deepen the response. Even though there is widespread use of therapeutic maintenance agents, the benefits and harms of these treatments are still uncertain. OBJECTIVES: To assess the effects and safety of maintenance therapy, including anti-CD20 monoclonal antibody, immunomodulatory drug therapy, anti-CD52 monoclonal antibody, Bruton tyrosine kinase inhibitor, and B-cell lymphoma-2 tyrosine kinase inhibitor, for individuals with CLL. SEARCH METHODS: We conducted a comprehensive literature search for randomised controlled trials (RCTs) with no language or publication status restrictions. We searched CENTRAL, MEDLINE, Embase, and three trials registers in January 2022 together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included RCTs with prospective identification of participants. We excluded cluster-randomised trials, cross-over trial designs, and non-randomised studies. We included studies comparing maintenance therapies with placebo/observation or head-to-head comparisons. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool for RCTs. We rated the certainty of evidence for the following outcomes using the GRADE approach: overall survival (OS), health-related quality of life (HRQoL), grade 3 and 4 adverse events (AEs), progression-free survival (PFS), treatment-related mortality (TRM), treatment discontinuation (TD), and all adverse events (AEs). MAIN RESULTS: We identified 11 RCTs (2393 participants) that met the inclusion criteria, including seven trials comparing anti-CD20 monoclonal antibodies (mAbs) (rituximab or ofatumumab) with observation in 1679 participants; three trials comparing immunomodulatory drug (lenalidomide) with placebo/observation in 693 participants; and one trial comparing anti-CD 52 mAbs (alemtuzumab) with observation in 21 participants. No comparisons of novel small molecular inhibitors were found. The median age of participants was 54.1 to 71.7 years; 59.5% were males. The type of previous induction treatment, severity of disease, and baseline stage varied among the studies. Five trials included early-stage symptomatic patients, and three trials included advanced-stage patients (Rai stage III/IV or Binet stage B/C). Six trials reported a frequent occurrence of cytogenic aberrations at baseline (69.7% to 80.1%). The median follow-up duration was 12.4 to 73 months. The risk of selection bias in the included studies was unclear. We assessed overall risk of performance bias and detection bias as low risk for objective outcomes and high risk for subjective outcomes. Overall risk of attrition bias, reporting bias, and other bias was low. Anti-CD20 monoclonal antibodies (mAbs): rituximab or ofatumumab maintenance versus observation Anti-CD20 mAbs maintenance likely results in little to no difference in OS (hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.73 to 1.20; 1152 participants; 3 studies; moderate-certainty evidence) and likely increases PFS significantly (HR 0.61, 95% CI 0.50 to 0.73; 1255 participants; 5 studies; moderate-certainty evidence) compared to observation alone. Anti-CD20 mAbs may result in: an increase in grade 3/4 AEs (rate ratio 1.34, 95% CI 1.06 to 1.71; 1284 participants; 5 studies; low-certainty evidence); little to no difference in TRM (risk ratio 0.82, 95% CI 0.39 to 1.71; 1189 participants; 4 studies; low-certainty evidence); a slight reduction to no difference in TD (risk ratio 0.93, 95% CI 0.72 to 1.20; 1321 participants; 6 studies; low-certainty evidence); and an increase in all AEs (rate ratio 1.23, 95% CI 1.03 to 1.47; 1321 participants; 6 studies; low-certainty evidence) compared to the observation group. One RCT reported that there may be no difference in HRQoL between the anti-CD20 mAbs (ofatumumab) maintenance and the observation group (mean difference -1.70, 95% CI -8.59 to 5.19; 480 participants; 1 study; low-certainty evidence). Immunomodulatory drug (IMiD): lenalidomide maintenance versus placebo/observation IMiD maintenance therapy likely results in little to no difference in OS (HR 0.91, 95% CI 0.61 to 1.35; 461 participants; 3 studies; moderate-certainty evidence) and likely results in a large increase in PFS (HR 0.37, 95% CI 0.19 to 0.73; 461 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. Regarding harms, IMiD maintenance therapy may result in an increase in grade 3/4 AEs (rate ratio 1.82, 95% CI 1.38 to 2.38; 400 participants; 2 studies; low-certainty evidence) and may result in a slight increase in TRM (risk ratio 1.22, 95% CI 0.35 to 4.29; 458 participants; 3 studies; low-certainty evidence) compared to placebo/observation. The evidence for the effect on TD compared to placebo is very uncertain (risk ratio 0.71, 95% CI 0.47 to 1.05; 400 participants; 2 studies; very low-certainty evidence). IMiD maintenance therapy probably increases all AEs slightly (rate ratio 1.41, 95% CI 1.28 to 1.54; 458 participants; 3 studies; moderate-certainty evidence) compared to placebo/observation. No studies assessed HRQoL. Anti-CD52 monoclonal antibodies (mAbs): alemtuzumab maintenance versus observation Maintenance with alemtuzumab may have little to no effect on PFS, but the evidence is very uncertain (HR 0.55, 95% CI 0.32 to 0.95; 21 participants; 1 study; very low-certainty evidence). We did not identify any study reporting the outcomes OS, HRQoL, grade 3/4 AEs, TRM, TD, or all AEs. AUTHORS' CONCLUSIONS: There is currently moderate- to very low-certainty evidence available regarding the benefits and harms of maintenance therapy in people with CLL. Anti-CD20 mAbs maintenance improved PFS, but also increased grade 3/4 AEs and all AEs. IMiD maintenance had a large effect on PFS, but also increased grade 3/4 AEs. However, none of the above-mentioned maintenance interventions show differences in OS between the maintenance and control groups. The effects of alemtuzumab maintenance are uncertain, coupled with a warning for drug-related infectious toxicity. We found no studies evaluating other novel maintenance interventions, such as B-cell receptor inhibitors, B-cell leukaemia-2/lymphoma-2 inhibitors, or obinutuzumab.

Effectiveness of Adaptive Support Ventilation in Facilitating Weaning from Mechanical Ventilation in Postoperative Patients.

OBJECTIVE: This meta-analysis aims to evaluate the effectiveness of adaptive support ventilation (ASV) in facilitating postoperative weaning from mechanical ventilation in cardiac surgery patients. DESIGN: A systematic review and meta-analysis to assess ASV in weaning postoperative cardiac surgery patients. Outcomes included early extubation, reintubation rates, time to extubation, and lengths of intensive care units and hospital stays. SETTING: We searched electronic databases from inception to March 2023 and included randomized controlled trials that compared ASV with conventional ventilation methods in this population. PARTICIPANTS: Postoperative cardiac surgery patients. MEASUREMENTS AND MAIN RESULTS: A random effects model was used for meta-analysis, and trial sequential analysis (TSA) was conducted to assess result robustness. The meta-analysis included 11 randomized controlled trials with a total of 1027 randomized patients. ASV was associated with a shorter time to extubation compared to conventional ventilation (random effects, mean difference -68.30 hours; 95% confidence interval, -115.50 to -21.09) with TSA providing a conclusive finding. While ASV indicated improved early extubation rates, no significant differences were found in reintubation rates or lengths of intensive care unit and hospital stays, with these TSA results being inclusive. CONCLUSIONS: ASV appears to facilitate a shorter time to extubation in postoperative cardiac surgery patients compared to conventional ventilation, suggesting benefits in accelerating the weaning process and reducing mechanical ventilation duration.

Different pedagogies for acquisition of knowledge and skill: a systematic review and network meta-analysis.

BACKGROUND: This network meta-analysis aimed to assess the efficacy of different educational methods for healthcare professionals. METHODS: A systematic literature search was conducted to identify relevant randomised controlled trials. The standardised mean difference (SMD) with 95% CI was estimated using network meta-analysis for knowledge acquisition and skill performance, and ranked the effects of different educational methods using the surface under the cumulative ranking area (SCURA) technique. RESULTS: Fifty-five randomised controlled trials including of 4292 participants were identified. Compared with no intervention, the results demonstrated all education methods achieved significant improvements in knowledge acquisition (SMD 1.73-2.66). Only education methods involving high fidelity virtual patient simulation reported significantly better skill performance (SMD 1.25-1.81). High fidelity virtual patient simulation plus self-directed learning was the most effective educational method both in terms of knowledge acquisition (SMD 2.66, 95% CI 1.4 to 4.12, SCURA 0.78) and skill performance (SMD 1.81, 95% CI 0.42 to 3.2, SCURA 0.89). CONCLUSIONS: Our study demonstrates all educational methods have positive effects on knowledge acquisition, but education methods involving high fidelity virtual patient simulation are better at improving skill performance than other methods.

Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer.

Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.

Proportional assist ventilation versus pressure support ventilation for weaning from mechanical ventilation in adults: a meta-analysis and trial sequential analysis.

BACKGROUND: Pressure support ventilation (PSV) is the prevalent weaning method. Proportional assist ventilation (PAV) is an assisted ventilation mode, which is recently being applied to wean the patients from mechanical ventilation. Whether PAV or PSV is superior for weaning remains unclear. METHODS: Eligible randomized controlled trials published before April 2020 were retrieved from databases. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs). RESULTS: Seven articles, involving 634 patients, met the selection criteria. Compared to PSV, PAV was associated with a significantly higher rate of weaning success (fixed-effect RR 1.16; 95% CI 1.07-1.26; I2 = 0.0%; trial sequential analysis-adjusted CI 1.03-1.30), and the trial sequential monitoring boundary for benefit was crossed. Compared to PSV, PAV was associated with a lower proportion of patients requiring reintubation (RR 0.49; 95% CI 0.28-0.87; I2 = 0%), a shorter ICU length of stay (MD - 1.58 (days), 95% CI - 2.68 to - 0.47; I2 = 0%), and a shorter mechanical ventilation duration (MD - 40.26 (hours); 95% CI - 66.67 to - 13.84; I2 = 0%). There was no significant difference between PAV and PSV with regard to mortality (RR 0.66; 95% CI 0.42-1.06; I2 = 0%) or weaning duration (MD - 0.01 (hours); 95% CI - 1.30-1.28; I2 = 0%). CONCLUSION: The results of the meta-analysis suggest that PAV is superior to PSV in terms of weaning success, and the statistical power is confirmed using trial sequential analysis.

Primary Fungal Prophylaxis in Hematological Malignancy: a Network Meta-Analysis of Randomized Controlled Trials.

Several new antifungal agents have become available for primary fungal prophylaxis of neutropenia fever in hematological malignancy patients. Our aim was to synthesize all evidence on efficacy and enable an integrated comparison of all current treatments. We performed a systematic literature review to identify all publicly available evidence from randomized controlled trials (RCT). We searched Embase, PubMed, the Cochrane Central Register of Controlled Clinical Trials, and the www.ClinicalTrials.gov website. In total, 54 RCTs were identified, including 13 treatment options. The evidence was synthesized using a network meta-analysis. Relative risk (RR) was adopted. Posaconazole was ranked highest in effectiveness for primary prophylaxis, being the most favorable in terms of (i) the RR for reduction of invasive fungal infection (0.19; 95% confidence interval [CI], 0.11 to 0.36) and (ii) the probability of being the best option (94% of the cumulative ranking). Posaconazole also demonstrated its efficacy in preventing invasive aspergillosis and proven fungal infections, with RR of 0.13 (CI, 0.03 to 0.65) and 0.14 (CI, 0.05 to 0.38), respectively. However, there was no significant difference among all of the antifungal agents in all-cause mortality and overall adverse events. Our network meta-analysis provided an integrated overview of the relative efficacy of all available treatment options for primary fungal prophylaxis for neutropenic fever in hematological malignancy patients under myelosuppressive chemotherapy or hematopoietic cell transplantation. On the basis of this analysis, posaconazole seems to be the most effective prophylaxis option until additional data from head-to-head randomized controlled trials become available.

Efficacy and Safety of Bevacizumab Combined with Mitomycin C or 5-Fluorouracil in Primary Trabeculectomy: A Meta-Analysis of Randomized Clinical Trials.

AIM: The objective of this study was to evaluate the efficacy and safety of bevacizumab combined with antimetabolite as an adjunctive therapy in primary trabeculectomy for glaucoma. MATERIALS AND METHODS: PubMed, Cochrane Library, and EMBASE were searched for relevant randomized controlled trials. Efficacy was evaluated by the postoperative mean intraocular pressure (IOP), complete success, and qualified success rates. Safety was evaluated by postoperative complications and surgical interventions. RESULTS: A total of 3 randomized controlled trials were included in the meta-analysis. The primary outcome was postoperative mean IOP at the 12-month follow-up. No significant difference in IOP was found between the bevacizumab + antimetabolite (mitomycin c or 5-fluorouracil) group and the antimetabolite alone group (weighted mean difference -0.27; 95% CI -1.38 to 0.83). There were no significant differences in complete success rates, qualified success rates, postoperative complications, and surgical interventions between the experimental treatment group and the conventional treatment group. CONCLUSIONS: Results of the meta-analysis demonstrated that the combination of bevacizumab (1.25 mg/mL) with a regular concentration of antimetabolite did not show more benefit or harm compared with using antimetabolite alone. Further randomized controlled trials are needed to evaluate the efficacy and safety of bevacizumab combined with lower concentrations and a shorter application time of antimetabolite.

Surviving Sepsis Campaign guidelines for a diver with DCI: case report.

Severe decompression illness (DCI) is an uncommon medical issue affecting divers and results mainly from rapid surfacing using inadequate decompression protocols. Massive gas embolism with central nervous system involvement often leads to a poor prognosis, with permanent residual neurologic defects. Moreover, DCI complicated with multiple organ dysfunction syndrome (MODS) is tremendously rare and difficult to cure, although hyperbaric oxygen (HBO2) therapy following the U.S. Navy Treatment Tables is a consensus. We report a case of severe DCI with profound shock and MODS after an initial treatment with HBO2 therapy using U.S. Navy Treatment Table 6A. Following the Surviving Sepsis Campaign Guidelines, low-dose hydrocortisone was administered. Although this treatment went against recommendation of the U.S. Navy Diving Manual, it resulted in a dramatic clinical improvement. After a second round of HBO2 treatments, the patient was discharged from hospital two weeks after the diving accident.

A meta-analysis of sutureless scleral-fixated intraocular lens versus retropupillary iris claw intraocular lens for the management of aphakia.

This study compared the visual outcomes and complications between sutureless scleral-fixated intraocular lens and iris claw intraocular lens implantation in aphakia without adequate capsule and/or zonule support. Studies comparing the clinical outcomes of scleral-fixated intraocular lens and iris claw intraocular lens implantation published until April 2022 were retrieved from the PubMed, EMBASE, Cochrane Library, and Google Scholar databases. The outcomes included postoperative final visual acuity, surgical time, surgery-induced astigmatism, and complications. The weighted mean difference and odds ratio were calculated. Two randomized controlled trials and five cohort studies, including 244 and 290 eyes in the scleral-fixated intraocular lens group and iris claw group, respectively, were included. Scleral-fixated intraocular lens implantation results in a better postoperative final corrected distance visual acuity compared with iris claw intraocular lens implantation; however, it is more time-consuming. Scleral-fixated intraocular lens implantation seems to have lesser incidences of surgery-induced astigmatism. Furthermore, both procedures have a similar complication rate. Therefore, based on current best evidence, these two procedures should be considered according to patient's conditions.

Efficacy and safety of intravitreal faricimab for neovascular age-related macular degeneration: a systematic review and meta-analysis.

We conducted a systematic review and meta-analysis to evaluate the visual, anatomical, and safety outcomes of the intravitreal faricimab, a novel vascular endothelial growth factor (VEGF)/angiopoietin-2 (Ang-2) bispecific agent, in neovascular age-related macular degeneration (nAMD) patients. The follow-up times in the included studies ranged from a minimum of 36 weeks to a maximum of 52 weeks. EMBASE, Ovid-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, the WHO ICTRP, ClinicalTrial.gov, the EU Clinical Trials Register, and Chinese Clinical Trial Registry (ChiCTR) were searched (The last literature search was performed on August 17, 2023) for randomized controlled trials (RCTs) comparing faricimab with control groups for neovascular age-related macular degeneration (nAMD). The risk of bias for eligible RCTs was independently assessed using the Cochrane Risk of Bias Tool by two authors (W.-T.Y. and C.-S.W.). The meta-analysis was conducted using Review Manager 5.4 software. The mean best corrected visual acuity (BCVA), central subfield thickness (CST), total choroidal neovascularization (CNV) area, and total lesion leakage were analyzed as continuous variables and the outcome measurements were reported as the weighted mean difference (WMD) with a 95% confidence interval (CI). The ocular adverse events and ocular serious adverse events were analyzed as dichotomous variables and the outcome measurements were analyzed as the odds ratios (ORs) with a 95% CI. Random-effects model was used in our study for all outcome synthesizing due to different clinical characteristics. Four RCTs with 1,486 patients were eligible for quantitative analysis. There was no statistically significant difference between intravitreal faricimab and anti-VEGF in BCVA [weighted mean difference (WMD) = 0.47; 95% CI: (- 0.17, 1.11)]. The intravitreal faricimab group showed numerically lower CST [WMD = - 5.96; 95% CI = (- 7.11, - 4.82)], total CNV area [WMD = - 0.49; 95% CI = (- 0.68, - 0.30)], and total lesion leakage [WMD = - 0.88; 95% CI = (- 1.08, - 0.69)] after intravitreal therapy compared with the intravitreal anti-VEGF group. There were no statistically significant differences between intravitreal faricimab and anti-VEGF in ocular adverse events (AEs) [pooled odds ratio (OR) = 1.10; 95% CI = (0.81, 1.49)] and serious adverse events (SAEs) [pooled OR = 0.84; 95% CI = (0.37, 1.90)]. The intravitreal bispecific anti-VEGF/angiopoietin 2 (Ang2) antibody faricimab with a extended injection interval was non-inferior to first-line anti-VEGF agents in BCVA. It was safe and had better anatomical recovery. Large, well-designed RCTs are needed to explore the potential benefit of extended faricimab for nAMD. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022327450).

Prediction of In-Hospital Cardiac Arrest in the Intensive Care Unit: Machine Learning-Based Multimodal Approach.

Background: Early identification of impending in-hospital cardiac arrest (IHCA) improves clinical outcomes but remains elusive for practicing clinicians. Objective: We aimed to develop a multimodal machine learning algorithm based on ensemble techniques to predict the occurrence of IHCA. Methods: Our model was developed by the Multiparameter Intelligent Monitoring of Intensive Care (MIMIC)-IV database and validated in the Electronic Intensive Care Unit Collaborative Research Database (eICU-CRD). Baseline features consisting of patient demographics, presenting illness, and comorbidities were collected to train a random forest model. Next, vital signs were extracted to train a long short-term memory model. A support vector machine algorithm then stacked the results to form the final prediction model. Results: Of 23,909 patients in the MIMIC-IV database and 10,049 patients in the eICU-CRD database, 452 and 85 patients, respectively, had IHCA. At 13 hours in advance of an IHCA event, our algorithm had already demonstrated an area under the receiver operating characteristic curve of 0.85 (95% CI 0.815-0.885) in the MIMIC-IV database. External validation with the eICU-CRD and National Taiwan University Hospital databases also presented satisfactory results, showing area under the receiver operating characteristic curve values of 0.81 (95% CI 0.763-0.851) and 0.945 (95% CI 0.934-0.956), respectively. Conclusions: Using only vital signs and information available in the electronic medical record, our model demonstrates it is possible to detect a trajectory of clinical deterioration up to 13 hours in advance. This predictive tool, which has undergone external validation, could forewarn and help clinicians identify patients in need of assessment to improve their overall prognosis.

The Efficacy and Safety of Tandem Transplant Versus Single Stem Cell Transplant for Multiple Myeloma Patients: A Systematic Review and Meta-Analysis.

While high-dose therapy and autologous stem cell transplant (ASCT) remain integral to the primary treatment of newly diagnosed transplant-elble multiple myeloma (MM) patients, the challenge of disease progression persists. The primary objective of this meta-analysis is to evaluate the efficacy and safety of tandem ASCT compared to single ASCT. We conducted a systematic review and meta-analysis of randomized controlled trials and observational studies comparing tandem ASCT with single ASCT in patients with newly diagnosed MM. We searched PubMed, EMBASE, Cochrane Library, and Clinical Trials databases for studies published up to January 2024. The primary outcomes were progression-free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and treatment-related mortality (TRM). We used a random-effects model to calculate pooled hazard ratios (HRs) and relative risks (RRs) with 95% confidence intervals (CIs). Study quality was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa Scale. Twelve studies involving 5057 patients met the inclusion criteria. Tandem ASCT was associated with a significantly higher CRR compared to single ASCT (HR 1.33, 95% CI 1.03-1.71, I2 = 15%), but no significant differences were observed in PFS (HR 0.75, 95% CI 0.42-1.34, I2 = 14%), OS (HR 0.60, 95% CI 0.33-1.10, I2 = 27%), or the ORR (RR 0.80, 95% CI 0.59-1.08, I2 = 33%). However, tandem ASCT was associated with a significantly higher risk of TRM (RR 1.78, 95% CI 1.00-3.18, I2 = 0%). Tandem ASCT improves the CRR but does not provide significant benefits in terms of PFS, OS, or ORR compared to single ASCT in patients with newly diagnosed MM. Moreover, tandem ASCT is associated with a higher risk of TRM. The decision to pursue tandem ASCT should be made on an individual basis, carefully weighing the potential benefits and risks in light of each patient's unique clinical situation. Future research should focus on identifying patient subgroups most likely to benefit from tandem ASCT and exploring strategies to optimize the efficacy and safety of this approach in the context of novel agent-based therapies.

Endovascular therapy for acute ischemic stroke in patients with active malignancy: a meta-analysis with trial sequential analysis.

BACKGROUND: Active malignancy has a poorer prognosis and more deaths in patients with acute ischemic stroke (AIS). The outcomes of endovascular therapy (EVT) remain controversial in patients with AIS and active malignancy. METHODS: We searched PubMed, Cochrane, and Embase for articles published up to June 1, 2022. The primary outcome was good functional outcome at 3 months and successful reperfusion between patients with cancer and AIS and control patients. The secondary and safety outcomes included mortality at 3 months, in-hospital mortality, symptomatic intracerebral hemorrhage (sICH), any ICH, and subarachnoid hemorrhage (SAH). RESULTS: Twelve studies involving 5944 patients with AIS secondary to EVT were included (389 patients having active malignancy). The OR of good functional outcome at 3 months was 0.53 (95% CI 0.41 to 0.67) between the two groups. The OR of successful reperfusion between the two groups was 0.90 (95% CI 0.63 to 1.30). Compared with patients without cancers, those with cancers had a higher risk of mortality at 3 months (OR 3.64; 95% CI 2.35 to 6.27) and in-hospital mortality (OR 3.46; 95% CI 1.71 to 7.01). Despite a higher point estimate regarding any ICH (OR 1.41; 95% CI 1.01 to 1.96) and SAH (OR 2.53; 95% CI 1.10 to 5.81), sICH (OR 0.85; 95% CI 0.51 to 1.42) was not significant. CONCLUSION: Although a quarter of patients with active malignancy and AIS regained functional independence, physicians and patients should consider whether to apply EVT in patients with active malignancy.

Effect and Optimal Timing of Extracorporeal Shock-Wave Intervention to Patients With Spasticity After Stroke: A Systematic Review and Meta-analysis.

OBJECTIVE: This study investigated the efficacy of extracorporeal shock wave therapy as well as the optimal intervention timing for extracorporeal shock wave therapy for patients with spasticity after stroke. DESIGN: A search of randomized controlled trials was conducted in different electronic databases. We performed a meta-analysis to measure the effect of extracorporeal shock wave therapy versus sham interventions on spasticity and limb functionality. The meta-regression analysis was performed to determine the adequate intervention timing of extracorporeal shock wave therapy. The follow-up period of the outcomes was divided into the short (<2 wks), mid (>2 wks and ≤4 wks), and long (>4 wks and ≤3 mos) terms. RESULTS: Thirteen studies with 677 participants were evaluated. Spasticity significantly improved throughout the follow-up duration. Limb functionality significantly improved in the short-term follow-up period. The meta-regression analysis showed that patients with stroke duration less than 45 mos may be benefited from extracorporeal shock wave therapy in improving limb function in all follow-up periods. CONCLUSIONS: Extracorporeal shock wave therapy is an effective method for reducing spasticity in patients with stroke, and the effect could be maintained for up to 3 mos. Its effects on limb functionality could persist for at least 2 wks. Patients who had stroke for less than 45 mos may have significant benefit from extracorporeal shock wave therapy in all follow-up periods.

Is Thrombocytopenia an In-Hospital Mortality Risk Factor among Patients with Acute Ischemic Stroke? A Propensity Score-Matched Analysis from the MIMIC-IV Database.

(1) Background: We aimed to evaluate the aspect of thrombocytopenia in patients with acute ischemic stroke (AIS); (2) Methods: Patients with AIS were recruited in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The thrombocytopenia was defined as a platelet blood count of less than 150 K/µL. We compared the patient characteristics and clinical outcomes using propensity score matching (PSM); (3) Results: Thrombocytopenia affected 151 out of the 1236 patients (12.2%). Patients with thrombocytopenia were older (70.5 ± 12.8 vs. 68.4 ± 14.4; SMD = 0.154) and had a higher Charlson comorbidity index (7.3 ± 2.5 vs. 6.7 ± 2.7; SMD = 0.228) and acute physiology score III (44.8 ± 21.0 vs. 38.2 ± 19.1; SMD = 0.328) than those without thrombocytopenia. The risk of in-hospital mortality did not increase linearly or nonlinearly with a lower platelet count (overall p value = 0.794; nonlinear p value = 0.646). After PSM, 147 pairs remained. Thrombocytopenia was not linked with in-hospital mortality (HR: 1.06, 95% CIs: 0.60-1.88); (4) Conclusions: We described the clinical characteristics of patients admitted for thrombocytopenia and AIS who did not receive reperfusion therapy; additionally, we found that thrombocytopenia was not an independent short-term risk factor of in-hospital mortality.

Progression-Free Survival Efficacy in Refractory/Relapsed Multiple Myeloma among Elderly Patients: A Systematic Review.

BACKGROUND: Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study aimed to evaluate treatment efficacy for these elderly patients. METHODS: We carried out a comprehensive review of the literature using a systematic approach. Initially, 4966 citations were retrieved and subsequently narrowed down to 13 eligible randomized controlled trials (RCTs) through our systematic review process from databases like Embase, PubMed, and Cochrane Library from 1 January 2000 to 31 December 2022. Evidence was collated through a frequentist network meta-analysis, using the hazard ratio (HR) for evaluation. RESULTS: Combined therapy of daratumumab, lenalidomide, and dexamethasone (DaraLenDex) was the preferred treatment for R/R MM elderly patients. Its strengths included an HR for progression-free survival (0.15; 95% CI: 0.09-0.25) and a 96% P-score. CONCLUSIONS: Our analysis suggests that, pending more comprehensive RCTs, DaraLenDex is the treatment with the highest efficacy for R/R MM in elderly patients.

Aqueous Lumican Correlates with Central Retinal Thickness in Patients with Idiopathic Epiretinal Membrane: A Proteome Study.

Idiopathic epiretinal membrane (iERM) is a pathological fibrocellular change in the vitreoretinal junction over the macular area; however, possible pathogenic mechanisms remain unclear. Changes in the differential protein composition of the aqueous humor (AH) may represent potential molecular changes associated with iERM. To gain new insights into the molecular mechanisms of iERM pathology, a sensitive label-free proteomics analysis was performed to compare AH protein expressions in patients with cataracts with or without iERM. This study employed nanoflow ultra-high-performance liquid chromatography-tandem mass spectrometry to investigate protein compositions of the AH obtained from individual human cataract eyes from 10 patients with iERM and 10 age-matched controls without iERM. Eight proteins were differentially expressed between the iERM and control samples, among which six proteins were upregulated and two were downregulated. A gene ontology (GO) analysis revealed that iERM was closely associated with several biological processes, such as immunity interactions, cell proliferation, and extracellular matrix remodeling. Additionally, multiple proteins, including lumican, cyclin-dependent kinase 13, and collagen alpha-3(VI) chain, were correlated with the central retinal thickness, indicating a multifactorial response in the pathogenic process of iERM. Changes in the AH level of lumican between iERM and control samples were also confirmed by an enzyme-linked immunosorbent assay. In conclusion, several pathological pathways involved in iERM were identified in the AH by a proteomic analysis, including immune reactions, cell proliferation, and remodeling of the extracellular matrix. Lumican is a potential aqueous biomarker for predicting iERM development and monitoring its progression. More clinical parameters also need to be identified to complete the analysis, and those could provide additional targets for treating and preventing iERM.

Effect of Lenalidomide Maintenance in Chronic Lymphocytic Leukemia: A Meta-Analysis and Trial-Sequential Analysis.

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disease in adults. Despite durable responses and sustained remission rates to frontline therapy, CLL is still incurable within standard therapy and eventually relapses. Maintenance therapies aim to achieve deep remission. However, the efficacy and safety of lenalidomide maintenance are still debated. Randomized controlled trials published before March 2022 were retrieved from databases. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Trial sequential analysis examined analytical power in primary outcomes. Secondary outcomes were Grade 3-4 neutropenia, treatment discontinuation (TD), serious adverse events (SAE), and fatal adverse events (FAE). Hazard (HR) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Four articles (733 patients) met the selection criteria. Lenalidomide maintenance was associated with a statistically significant effect in prolonging PFS (HR, 0.43; 95% CI, 0.28-0.68; I2 = 57%) and higher proportion of SAE (OR 4.64; 95% CI 2.96-7.26; I2 = 0%) and exhibited no difference in OS (HR, 0.62; 95% CI, 0.29-1.30; I2 = 52%) observation/placebo. It showed no significant difference compared with observation/placebo regarding Grade 3-4 neutropenia (OR 2.30; 95% CI 0.84-6.28; I2 = 81%), TD (OR 0.76; 95% CI 0.29-1.99; I2 = 84%), and FAE (OR 0.86; 95% CI 0.28-2.63; I2 = 0%). Lenalidomide maintenance can prolong PFS in CLL. Further studies should verify its effect on OS.