Cost-Effectiveness of Sleep Apnea Diagnosis and Treatment in Hospitalized Persons With Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: To assess the cost-effectiveness of alternative approaches to diagnose and treat obstructive sleep apnea (OSA) in patients with traumatic brain injury (TBI) during inpatient rehabilitation. SETTING: Data collected during the Comparison of Sleep Apnea Assessment Strategies to Maximize TBI Rehabilitation Participation and Outcome (C-SAS) clinical trial (NCT03033901) on an inpatient rehabilitation TBI cohort were used in this study. STUDY DESIGN: Decision tree analysis was used to determine the cost-effectiveness of approaches to diagnosing and treating sleep apnea. Costs were determined using 2021 Centers for Medicare and Medicaid Services reimbursement codes. Effectiveness was defined in terms of the appropriateness of treatment. Costs averted were extracted from the literature. A sensitivity analysis was performed to account for uncertainty. Analyses were performed for all severity levels of OSA and a subgroup of those with moderate to severe OSA. Six inpatient approaches using various phases of screening, testing, and treatment that conform to usual care or guideline-endorsed interventions were evaluated: (1) usual care; (2) portable diagnostic testing followed by laboratory-quality testing; (3) screening with the snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and male gender (STOP-Bang) questionnaire; (4) Multivariable Apnea Prediction Index (MAPI) followed by portable diagnostic testing and laboratory-quality testing; (5) laboratory-quality testing for all; and (6) treatment for all patients. MAIN MEASURES: Cost, Effectiveness, and Incremental Cost-Effectiveness Ratio (ICER). RESULTS: Phased approaches utilizing screening and diagnostic tools were more effective in diagnosing and allocating treatment for OSA than all alternatives in patients with mild to severe and moderate to severe OSA. Usual care was more costly and less effective than all other approaches for mild to severe and moderate to severe OSA. CONCLUSIONS: Diagnosing and treating OSA in patients with TBI is a cost-effective strategy when compared with usual care.

PPAR agonists as add-on treatment with metformin in management of type 2 diabetes: a systematic review and meta-analysis.

The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.

ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Relapsed Refractory Multiple Myeloma after Failure of Chimeric Antigen Receptor T-Cell Therapy.

Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the management of relapsed and/or refractory multiple myeloma (RRMM). However, CAR-T treatment failure is not uncommon and remains a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post CAR-T failures in RRMM. The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between September 2023 and December 2023 to determine the myeloma, transplantation and cellular therapy physicians' practice patterns for surveillance, diagnosis, and management of CAR-T failure. The intent of this survey was to understand clinical practice patterns and identify areas for further investigation. E-mail surveys were sent to 1311 ASTCT physician members and 80 (6.1%) respondents completed the survey who identified as 58% white, 66% male, and 51% had >10 years of clinical experience. Eighty-nine percent of respondents were affiliated with university/teaching centers; 56% had myeloma-focused transplantation and/or cellular therapy practices. Post-CAR-T surveillance laboratory studies were commonly done every 4 weeks, while surveillance bone marrow biopsies and/or imaging surveillance were most commonly done at 3 months. Sixty-four percent of respondents would often or always consider biopsy or imaging to confirm relapse. The most popular post- CAR-T-failure rescue regimen was a GPRC5D-directed immunotherapy (30%) for relapses occurring ≤3 months and BCMA-directed bispecific therapies (32.5%) for relapses >3 months. Forty-one percent of respondents endorsed post-CAR-T prolonged cytopenia as "often" or "always" being a barrier to next-line therapy; 53% had offered stem cell boost as a mitigation approach. Substantial cross-center variation in practice patterns raises the need for collaborative studies and expert clinical recommendations to describe best practices for post CAR-T disease surveillance, optimal work-up for treatment failure, and choice of rescue therapies.

Need for Gastrostomy Tube in Periviable Infants.

OBJECTIVE: We sought to identify clinical and demographic factors associated with gastrostomy tube (g-tube) placement in periviable infants. STUDY DESIGN: We conducted a single-center retrospective cohort study of live-born infants between 22 and 25 weeks' gestation. Infants not actively resuscitated and those with congenital anomalies were excluded from analysis. RESULTS: Of the 243 infants included, 158 survived until discharge. Of those that survived to discharge, 35 required g-tube prior to discharge. Maternal race/ethnicity (p = 0.006), intraventricular hemorrhage (p = 0.013), periventricular leukomalacia (p = 0.003), bronchopulmonary dysplasia (BPD; p ≤ 0.001), and singleton gestation (p = 0.009) were associated with need for gastrostomy. In a multivariable logistic regression, maternal Black race (Odds Ratio [OR] 2.88; 95% confidence interval [CI] 1.11-7.47; p = 0.029), singleton gestation (OR 3.99; 95% CI 1.28-12.4; p = 0.017) and BPD (zero g-tube placement in the no BPD arm; p ≤ 0.001) were associated with need for g-tube. CONCLUSION: A high percentage of periviable infants surviving until discharge require g-tube at our institution. In this single-center retrospective study, we noted that maternal Black race, singleton gestation, and BPD were associated with increased risk for g-tube placement in infants born between 22 and 25 weeks' gestation. The finding of increased risk with maternal Black race is consistent with previous reports of racial/ethnic disparities in preterm morbidities. Additional studies examining factors associated with successful achievement of oral feedings in preterm infants are necessary and will inform future efforts to advance equity in newborn health. KEY POINTS: · BPD, singleton birth, and Black race are associated with need for g-tube in periviable infants.. · Severe intraventricular hemorrhage is associated with increased mortality or g-tube placement in periviable infants.. · Further investigation into the relationship between maternal race and g-tube placement is warranted..

A US Multicenter Collaborative Study on Outcomes of Hematopoietic Cell Transplantation in Hepatosplenic T-Cell Lymphoma.

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and aggressive type of peripheral T-cell lymphoma with median overall survival (OS) of approximately 1 year. Data on the effectiveness of hematopoietic cell transplantation (HCT) is limited, as is the choice between autologous HCT (auto-HCT) and allogeneic HCT (allo-HCT) in the treatment of this disease. To evaluate the outcome of patients with HSTCL who underwent either auto-HCT or allo-HCT, we performed a multi-institutional retrospective cohort study to assess outcomes of HCT in HSTCL patients. Fifty-three patients with HSTCL were included in the study. Thirty-six patients received an allo-HCT and 17 received an auto-HCT. Thirty-five (66%) were males. Median age at diagnosis was 38 (range 2 to 64) years. Median follow-up for survivors was 75 months (range 8 to 204). The median number of prior lines of therapy was 1 (range 1 to 4). Median OS and progression-free survival (PFS) for the entire cohort were 78.5 months (95% CI: 25 to 79) and 54 months (95% CI: 18 to 75), respectively. There were no significant differences in OS (HR: 0.63, 95% CI: 0.28 to 1.45, P = .245) or PFS (HR: 0.7, 95% CI: 0.32 to 1.57, P = .365) between the allo-HCT and auto-HCT groups, respectively. In the allo-HCT group, the 3-year cumulative incidence of relapse was 35% (95% CI: 21 to 57), while 3-year cumulative incidence of NRM was 16% (95% CI: 7 to 35). In the auto-HCT group, the 3-year cumulative incidence of relapse and NRM were 43% (95% CI: 23 to 78) and 14% (95% CI: 4 to 52), respectively. Both Auto-HCT and Allo-HCT are effective consolidative strategies in patients with HSTCL, and patients should be promptly referred for HCT evaluation.

Efficacy of Intravenous Iron in Patients with Heart Failure with Reduced Ejection Fraction and Iron Deficiency: A Systematic Review and Meta-Analysis of Randomized Control Trials.

BACKGROUND: The European Society of Cardiology (ESC) provided a focused update to the 2021 Guideline for the Management of Heart Failure, now providing a 1A recommendation for intravenous iron in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID). However, the findings from randomized controlled trials (RCT) are mixed. This systematic review of RCTs aims to provide an update and synthesize the evidence addressing the association of intravenous iron with patient-based outcomes in patients with HFrEF and ID. METHODS: Any RCT evaluating the effect of intravenous iron in patients with HFrEF and ID was eligible for inclusion. A complete search of the EMBASE and PubMed databases was conducted from inception until 15 September 2023. The primary outcome was the composite of the quality of life (QoL) questionnaires, while the secondary outcomes included first heart failure (HF) hospitalizations and all-cause mortality. Data extraction was performed independently by two reviewers. Data were pooled using a random-effects model. RESULTS: Of the 1035 references, 15 RCTs enrolling 6649 patients were included in this study. Intravenous iron was associated with significant improvement in the composite of QoL (standardized mean difference - 1.36, 95% confidence interval [CI] - 2.24 to - 0.48; p = 0.002), a significant reduction in first HF hospitalizations (hazard ratio [HR] 0.73, 95% CI 0.56-0.95; p = 0.02), and with no change in all-cause mortality (HR 0.90, 95% CI 0.79-1.03; p = 0.12). The certainty of the evidence ranged from moderate to very low. CONCLUSION: Intravenous iron is possibly associated with improved QoL and reduced HF hospitalizations, without impacting all-cause mortality. These findings not only support the use of intravenous iron in patients with HFrEF but also emphasize the need for well-designed and executed RCTs with granular outcome reporting and powered sufficiently to address the impact of intravenous iron on mortality in patients with HFrEF and ID. REGISTRATION: PROSPERO identifier number CRD42023389.

Efficacy of Autologous and Allogeneic Hematopoietic Cell Transplantation in Adults with Acute Promyelocytic Leukemia: Results of a Systematic Review and Meta-Analysis.

Despite therapeutic advances for acute promyelocytic leukemia (APL) with the emergence of all-trans retinoic acid, arsenic trioxide, and gemtuzumab-ozogamycin, approximately 10% of patients still experience disease relapse, typically occurring within 24 to 36 months following completion of front-line treatment. Traditionally, both allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) have been considered reasonable treatment options for relapsed APL; however, no randomized controlled studies have been conducted comparing allo-HCT and auto-HCT in patients with relapsed APL. We performed a systematic review/meta-analysis to assess the totality of evidence pertaining to allo-HCT or auto-HCT in relapsed APL. Our search identified 1158 references, of which 23 met our inclusion criteria. While acknowledging the limitations of comparing these 2 treatment modalities indirectly, based on results from separate meta-analyses, it appears that pooled rates of event-free survival (71% versus 54%), progression-free survival (63% versus 43%), and overall survival (82% versus 58%) are higher after auto-HCT. This difference can be explained in part by the higher risk of pooled nonrelapse mortality (NRM) in patients undergoing allo-HCT (29% versus 5%), owing to inherent risks associated with this modality. In the absence of a randomized prospective clinical trial comparing allo-HCT and auto-HCT, our results show that both modalities are acceptable in patients with relapsed APL. The higher pooled NRM rate with allo-HCT is an important consideration when choosing this option. Additionally, the comparable pooled relapse rate for auto-HCT and allo-HCT (24% versus 23%) provides a rationale for evaluating post-HCT consolidative strategies to mitigate this risk.

Efficacy of 24 hours versus 5 days of prophylactic antibiotics for the prevention of surgical site infection in outpatient elective facial plastic surgery.

Background: The discovery of penicillin marked a paradigm shift in medicine with the ability to treat previously life-threatening infections. Increasing antibiotic resistance as well as the risk of adverse reactions to antibiotics, however, creates pressures for judicious use. There continues to be debate about the role of prophylactic antibiotics in facial plastic surgery. This study explores the role of prophylactic antibiotic administration in elective outpatient facial plastic surgery by comparing 5 days versus 24 hours of antibiotic prophylaxis. Method: A retrospective cohort study of all consecutive patients undergoing cosmetic procedures at an outpatient facial plastic surgical center who received either 5 days or 24 hours of prophylactic antibiotics was performed. The primary outcome was the need for postoperative antibiotics within 6 weeks of surgery. Results: 204 patients met the inclusion criteria: 104 in the 5-day group and 100 in the 24-hour prophylaxis group. The overall infection rate was 3.4%: 3% in the 24-hour group and 3.8% in the 5-day group (p = 0.77). Subgroup analysis of clean-contaminated cases (n = 85) showed the rate of postoperative infections was 4.3%, all within the 5-day group. In clean cases (n = 119), the rate of postoperative infections was 4.2% (n = 5): 4.8% (n = 3) in the 24-hour group versus 3.5% (n = 2) in the 5-day group. Conclusions: The results show that decreasing the duration of antibiotics was not associated with an increased risk of postoperative infection. Given that antibiotics are an increasingly precious commodity with rising rates of resistance, this study supports the use of decreasing postoperative antibiotics to 24 hours.

AagingBase: a comprehensive database of anti-aging peptides.

The process of aging is an intrinsic and inevitable aspect of life that impacts every living organism. As biotechnological advancements continue to shape our understanding of medicine, peptide therapeutics have emerged as a promising strategy for anti-aging interventions. This is primarily due to their favorable attributes, such as low immunogenicity and cost-effective production. Peptide-based treatments have garnered widespread acceptance and interest in aging research, particularly in the context of age-related therapies. To effectively develop anti-aging treatments, a comprehensive understanding of the physicochemical characteristics of anti-aging peptides is essential. Factors such as amino acid composition, instability index, hydrophobic areas and other relevant properties significantly determine their efficacy as potential therapeutic agents. Consequently, the creation of 'AagingBase', a comprehensive database for anti-aging peptides, aims to facilitate research on aging by leveraging the potential of peptide therapies. AagingBase houses experimentally validated 282 anti-aging peptides collected from 54 research articles and 236 patents. Employing state-of-the-art computational techniques, the acquired sequences have undergone rigorous physicochemical calculations. Furthermore, AagingBase presents users with various informative analyses highlighting atomic compositions, secondary structure fractions, tertiary structure, amino acid compositions and frequencies. The database also offers advanced search and filtering options and similarity search, thereby aiding researchers in understanding their biological functions. Hence, the database enables efficient identification and prioritization of potential peptide candidates in geriatric medicine and holds immense potential for advancing geriatric medicine research and innovations. AagingBase can be accessed without any restriction. Database URL: https://project.iith.ac.in/cgntlab/aagingbase/.

Size Matching Deceased Donor Livers: The Tampa General Measurement System.

BACKGROUND: No reliable or standardized system exists for measuring the size of deceased donor livers to determine whether they will fit appropriately into intended recipients. METHODS: This retrospective, single-center study evaluated the efficacy of Tampa General Hospital's size-matching protocol for consecutive, deceased donor liver transplantations between October 2021 and November 2022. Our protocol uses cross-sectional imaging at the time of organ offer to compare the donor's right hepatic lobe size with the recipient's right hepatic fossa. Outcomes were analyzed, including large-for-size syndrome, small-for-size syndrome, early allograft dysfunction, primary nonfunction, graft survival, and patient survival. RESULTS: We included 171 patients in the study. The donor liver physically fit in all the patients except one whose pretransplant imaging was outdated. One patient (0.6%) had large-for-size syndrome, none had small-for-size syndrome, 15 (10%) had early allograft dysfunction, and none had primary nonfunction. There were 11 (7%) patient deaths and 11 (7%) graft failures. CONCLUSION: Our measurement system is fast and effective. It reliably predicts whether the donor liver will fit in the intended recipient and is associated with low rates of early allograft dysfunction.

Tubulin CFEOM mutations both inhibit or activate kinesin motor activity.

Kinesin-mediated transport along microtubules is critical for axon development and health. Mutations in the kinesin Kif21a, or the microtubule subunit ß-tubulin, inhibit axon growth and/or maintenance resulting in the eye-movement disorder congenital fibrosis of the extraocular muscles (CFEOM). While most examined CFEOM-causing ß-tubulin mutations inhibit kinesin-microtubule interactions, Kif21a mutations activate the motor protein. These contrasting observations have led to opposed models of inhibited or hyperactive Kif21a in CFEOM. We show that, contrary to other CFEOM-causing ß-tubulin mutations, R380C enhances kinesin activity. Expression of ß-tubulin-R380C increases kinesin-mediated peroxisome transport in S2 cells. The binding frequency, percent motile engagements, run length and plus-end dwell time of Kif21a are also elevated on ß-tubulin-R380C compared with wildtype microtubules in vitro. This conserved effect persists across tubulins from multiple species and kinesins from different families. The enhanced activity is independent of tail-mediated kinesin autoinhibition and thus utilizes a mechanism distinct from CFEOM-causing Kif21a mutations. Using molecular dynamics, we visualize how ß-tubulin-R380C allosterically alters critical structural elements within the kinesin motor domain, suggesting a basis for the enhanced motility. These findings resolve the disparate models and confirm that inhibited or increased kinesin activity can both contribute to CFEOM. They also demonstrate the microtubule's role in regulating kinesins and highlight the importance of balanced transport for cellular and organismal health.

MyeloDB: a multi-omics resource for multiple myeloma.

Multiple myeloma (MM) is a common type of blood cancer affecting plasma cells originating from the lymphoid B-cell lineage. It accounts for about 10% of all hematological malignancies and can cause significant end-organ damage. The emergence of genomic technologies such as next-generation sequencing and gene expression analysis has opened new possibilities for early detection of multiple myeloma and identification of personalized treatment options. However, there remain significant challenges to overcome in MM research, including integrating multi-omics data, achieving a comprehensive understanding of the disease, and developing targeted therapies and biomarkers. The extensive data generated by these technologies presents another challenge for data analysis and interpretation. To bridge this gap, we have developed a multi-omics open-access database called MyeloDB. It includes gene expression profiling, high-throughput CRISPR-Cas9 screens, drug sensitivity resources profile, and biomarkers. MyeloDB contains 47 expression profiles, 3 methylation profiles comprising a total of 5630 patient samples and 25 biomarkers which were reported in previous studies. In addition to this, MyeloDB can provide significant insight of gene mutations in MM on drug sensitivity. Furthermore, users can download the datasets and conduct their own analyses. Utilizing this database, we have identified five novel genes, i.e., CBFB, MANF, MBNL1, SEPHS2, and UFM1 as potential drug targets for MM. We hope MyeloDB will serve as a comprehensive platform for researchers and foster novel discoveries in MM. MyeloDB Database URL: https://project.iith.ac.in/cgntlab/myelodb/ .

A systematic critical appraisal of clinical practice guidelines of antithrombotic agents in gastrointestinal endoscopy using the AGREE II tool.

BACKGROUND AND AIM: The quality of clinical practice guidelines (CPGs) for the management of antithrombotic agents in patients undergoing gastrointestinal (GI) endoscopy has not been systematically appraised. The goal of this study was to evaluate the methodological quality of CPGs for the management of antithrombotic agents in periendoscopic period published within last 6 years. METHODS: A systematic search of PubMed and Embase databases was performed to identify eligible CPGs published between January 1, 2016, and April 14, 2022, addressing the management of antithrombotic agents in the periendoscopic period. The quality of the CPG was independently assessed by six reviewers using the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument. Domain scores were considered of sufficient quality when > 60% and of good quality when > 80%. RESULTS: The search yielded 343 citations, of which seven CPGs published by the gastroenterology associations in Asia (n = 3), Europe (n = 2), and North America (n = 2) were included for the critical appraisal. The overall median score for the AGREE II domains was 93% (interquartile range [IQR] 11%) for scope and purpose, 79% (IQR 61%) for stakeholder involvement, 79% (IQR 36%) for rigor of development, 100% (IQR 14%) for clarity of presentation, 32% (IQR 36%) for applicability, 93% (IQR 29%) for editorial independence, and 86% (IQR 29%) for overall assessment. CONCLUSIONS: The findings show that the overall methodological quality of the CPGs for the management of antithrombotic agents in the periendoscopic period varies across the domains. There is significant scope for improvement in the methodological rigor and applicability of CPGs.

Sirolimus Is an Acceptable Alternative to Tacrolimus for Graft-versus-Host Disease Prophylaxis after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT.

Efficacy of Decision Aids in The Use of Left Ventricular Assist Device in Patients With Advanced Heart Failure: A Systematic Review and Meta-Analysis of Randomized Control Trials.

Although left ventricular assist device (LVAD) implantation can improve survival in patients with end-stage heart failure, it is not without risk. Numerous complications are possible, and durable support requires substantial lifestyle changes. The use of various knowledge-assessment tools may allow for more informed patient decisions. To synthesize the totality of the evidence, we conducted a systematic review and meta-analysis to summarize the efficacy of decision aid (DA) use in patients with advanced heart failure who are eligible for LVAD. Any randomized controlled trial (RCT) evaluating the efficacy of DAs in patients considering LVAD was eligible for inclusion. A complete search of EMBASE and PubMed was conducted from the start until June 8, 2023. The primary outcome was patients' LVAD knowledge. Data extraction was performed independently by 2 reviewers. Data were pooled using a random-effects model. Of the 575 references, 2 RCTs randomizing 490 patients were included in this study. DAs were associated with no significant change in LVAD knowledge (standardized mean difference 0.07, 95% confidence interval -0.24 to 0.39, p = 0.64) or decisional conflict (mean difference -1.48, 95% confidence interval -5.28 to 2.32, p = 0.45). The certainty of the evidence ranged from moderate to very low. The use of DAs in LVAD-eligible patients with advanced heart failure resulted in no difference in patients' knowledge of LVAD after LVAD education. The findings from this study will aid in the power analysis of a well-designed RCT to evaluate and encourage further investigation into the efficacy and relevance of DAs in preparing patients for a life with LVAD.

Quality of Pancreatic Cyst Clinical Practice Guidelines.

BACKGROUND: There are various published clinical practice guidelines (CPGs) for the management of pancreatic cystic lesions. However, the quality of these guidelines has not been systematically appraised. This study aimed to evaluate the quality of CPGs published in the last 5 years for the management of pancreatic cysts. METHODS: A systematic search of the PubMed database for eligible CPGs published between January 1, 2016 and November 17, 2021, using a sensitive filter. The quality of the CPGs was independently evaluated using the Appraisal of Guidelines for Research & Evaluation II instrument, with domain scores considered sufficient quality if >60% and good quality if >80%. RESULTS: The search yielded 4 eligible CPGs out of 426 citations. The scores varied for different domains for each CPG, with the overall median score being 79% for scope and purpose, 26% for stakeholder involvement, 51% for rigor of development, 69% for clarity of presentation, 14% for applicability, and 75% for editorial independence. CONCLUSIONS: The study revealed that the quality of the CPGs for pancreatic cyst management in adults remains moderate at best. Patient representatives were not involved in any of the CPG development process. There is a significant scope for improvement in methodological rigor and clarity of presentation.

A Systematic Critical Appraisal of Clinical Practice Guidelines in Heart Failure Using the AGREE II Tool.

Multiple clinical practice guidelines (CPGs) for heart failure management have been published to provide the best practices regarding the use of foundational therapies to reduce morbidity and mortality in this patient population. However, a critical appraisal of these heart failure guidelines has not been performed. This systematic review aimed to assess the methodological quality of current CPGs in the management of patients with heart failure. A comprehensive search of EMBASE and PubMed was conducted to identify CPGs published between January 1, 2021 and September 8, 2022. Any CPGs published in the last 2 years addressing the management of heart failure were eligible for inclusion. The methodological quality of the CPGs was assessed using the AGREE II (Appraisal of Guidelines for Research & Evaluate II) instrument. The initial search yielded 3,269 citations, of which, 6 CPGs were included. A total of 2 CPGs were each published by the cardiology associations in North America and Asia and 1 each in Europe and South America. The overall median score for the AGREE II domains were 100% for scope and purpose, 71% for stakeholder involvement, 71% for the rigor of development, 100% for clarity of presentation, 43% for applicability, 100% for editorial independence, and 64% for overall assessment. CPG developers would benefit from the use of a standardized approach to the development of CPGs and use the contents of the AGREE II tool to improve the methodological rigor, reporting, and applicability of CPGs.

ASTCT Clinical Practice Recommendations for Transplantation and Cellular Therapies in Diffuse Large B Cell Lymphoma.

Autologous hematopoietic cell transplantation (auto-HCT) has long been the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with the recent approval of CD19-directed CAR-T therapy in the second-line setting in high-risk groups (primary refractory and early relapse [≤12 months]). Consensus on the contemporary role, optimal timing, and sequencing of HCT and cellular therapies in DLBCL is lacking; therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook this project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with a few key statements as follows: (1) in the first-line setting, there is no role for auto-HCT consolidation for patients achieving complete remission (CR) following R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) or similar therapy in non-double-hit/triple-hit cases (DHL/THL) and in DHL/THL cases receiving intensive induction therapies, but auto-HCT may be considered in eligible patients receiving R-CHOP or similar therapies in DHL/THL cases; (2) auto-HCT consolidation with thiotepa-based conditioning is standard of care for eligible patients with primary central nervous system lymphoma achieving CR with first-line therapy; and (3) in the primary refractory and early relapse setting, the preferred option is CAR-T therapy, whereas in late relapse (>12 months), consolidation with auto-HCT is recommended for patients achieving chemosensitivity to salvage therapy (complete or partial response), and CAR-T therapy is recommended for those not achieving remission. These clinical practice recommendations will serve as a tool to guide clinicians managing patients with newly diagnosed and R/R DLBCL.

Effects of combined treatment of probiotics and metformin in management of type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Lifestyle changes and dietary intervention, including the use of probiotics, can modulate dysbiosis of gut microbiome and contribute to the management of type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to assess the efficacy of metformin plus probiotics versus metformin alone on outcomes in patients with T2DM. METHODS: We searched MEDLINE and EMBASE from inception to February 2023 to identify all randomized controlled trials (RCTs), which compared the use of metformin plus probiotics versus metformin alone in adult patients with T2DM. Data were summarized as mean differences (MD) with 95 % confidence interval (CI) and pooled under the random effects model. FINDINGS: Fourteen RCTs (17 comparisons, 1009 patients) were included in this systematic review. Pooled results show a significant decrease in fasting glucose (FG) (MD = -0.64, 95 % CI = -1.06, -0.22) and HbA1c (MD = -0.29, 95 % CI = -0.47, -0.10) levels in patients with T2DM treated with metformin plus probiotics versus metformin alone. The addition of probiotics to metformin resulted in lower odds of gastrointestinal adverse events (Odds ratio = 0.18, 95 % CI = 0.09, 0.3.8; I2 = 0 %). CONCLUSIONS: The addition of probiotics to metformin therapy is associated with improvement in T2DM outcomes. However, high-quality and adequately reported RCTs are needed in the future to confirm our findings.