Comparative efficacy of tandem autologous versus autologous followed by allogeneic hematopoietic cell transplantation in patients with newly diagnosed multiple myeloma: a systematic review and meta-analysis of randomized controlled trials

Background Despite advances in understanding of clinical, genetic, and molecular aspects of multiple myeloma (MM) and availability of more effective therapies, MM remains incurable. The autologous-allogeneic (auto-allo) hematopoietic cell transplantation (HCT) strategy is based on combining cytoreduction from high-dose (chemo- or chemoradio)-therapy with adoptive immunotherapy. However, conflicting results have been reported when an auto-allo HCT approach is compared to tandem autologous (auto-auto) HCT. A previously published meta-analysis has been reported; however, it suffers from serious methodological flaws. Methods A systematic search identified 152 publications, of which five studies (enrolling 1538 patients) met inclusion criteria. All studies eligible for inclusion utilized biologic randomization. Results Assessing response rates by achievement of at least a very good partial response did not differ among the treatment arms [risk ratio (RR) (95% CI) = 0.97 (0.87-1.09), p = 0.66]; but complete remission was higher in the auto-allo HCT arm [RR = 1.65 (1.25-2.19), p = 0.0005]. Event-free survival did not differ between auto-allo HCT group versus auto-auto HCT group using per-protocol analysis [hazard ratio (HR) = 0.78 (0.58-1.05)), p = 0.11] or using intention-to-treat analysis [HR = 0.83 (0.60-1.15), p = 0.26]. Overall survival (OS) did not differ among these treatment arms whether analyzed on per-protocol [HR = 0.88 (0.33-2.35), p = 0.79], or by intention-to-treat [HR = 0.80 (0.48-1.32), p = 0.39] analysis. Non-relapse mortality (NRM) was significantly worse with auto-allo HCT [RR (95%CI) = 3.55 (2.17-5.80), p \u3c 0.00001]. Conclusion Despite higher complete remission rates, there is no improvement in OS with auto-allo HCT; but this approach results in higher NRM in patients with newly diagnosed MM. At present, totality of evidence suggests that an auto-allo HCT approach for patients with newly diagnosed myeloma should not be offered outside the setting of a clinical trial

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.</p

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.</p

Comparisons of commonly used front-line regimens on survival outcomes in patients aged 70 years and older with acute myeloid leukemia

In older patients with acute myeloid leukemia, the more frequent presence of biologically inherent therapy-resistant disease and increased comorbidities translate to poor overall survival and therapeutic challenges. Optimal front-line therapies for older patients with acute myeloid leukemia remain controversial. We retrospectively evaluated survival outcomes in 980 elderly (≥70 years) acute myeloid leukemia patients from a single institution between 1995 and 2016. Four treatment categories were compared: high-intensity (daunorubicin/cytarabine or equivalent), hypomethylating agent, low-intensity (low-dose cytarabine or similar without hypomethylating agents), and supportive care therapy (including hydroxyurea). At a median follow up of 20.5 months, the median overall survival for the entire cohort was 7.1 months. Multivariate analysis identified secondary acute myeloid leukemia, poor-risk cytogenetics, performance status, front-line therapy, age, white blood cell count, platelet count, and hemoglobin level at diagnosis as having an impact on survival. High-intensity therapy was used in 360 patients (36.7%), hypomethylating agent in 255 (26.0%), low-intensity therapy in 91 (9.3%), and supportive care in 274 (28.0%). Pairwise comparisons between hypomethylating agent therapy and the three other treatment groups demonstrated statistically significant superior median overall survival with hypomethylating agent [14.4 months) vs. high-intensity therapy 10.8 months, hazard ratio 1.35, 95% confidence interval (CI): 1.10-1.65; P =0.004], low-intensity therapy (5.9 months, hazard ratio 2.01, 95%CI: 1.53-2.62;

Endothelial glycocalyx-associated molecules as potential serological markers for sepsis-associated encephalopathy: A systematic review and meta-analysis.

BackgroundSepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system infection. The endothelial glycocalyx is a dynamic mesh containing heparan sulfate linked to proteoglycans and glycoproteins, including selectins and vascular/intercellular adhesion molecules (V/I-CAMs), which protects the endothelium while mediating mechano-signal transduction between the blood and vascular wall. During severe inflammatory states, components of the glycocalyx are shed into the circulation and can be detected in soluble forms. Currently, SAE remains a diagnosis of exclusion and limited information is available on the utility of glycocalyx-associated molecules as biomarkers for SAE. We set out to synthesize all available evidence on the association between circulating molecules released from the endothelial glycocalyx surface during sepsis and sepsis-associated encephalopathy.MethodsMEDLINE (PubMed) and EMBASE were searched since inception until May 2, 2022 to identify eligible studies. Any comparative observational study: i) evaluating the association between sepsis and cognitive decline and ii) providing information on level of circulating glycocalyx-associated molecules was eligible for inclusion.ResultsFour case-control studies with 160 patients met the inclusion criteria. Meta-analysis of biomarkers ICAM-1 (SMD 0.41; 95% CI 0.05-0.76; p = 0.03; I2 = 50%) and VCAM-1 (SMD 0.55; 95% CI 0.12-0.98; p = 0.01; I2 = 82%) revealed higher pooled mean concentration in patients with SAE compared to the patients with sepsis alone. Single studies reported elevated levels of P-selectin (MD 0.80; 95% CI -17.77-19.37), E-selectin (MD 96.40; 95% Cl 37.90-154.90), heparan sulfate NS2S (MD 19.41; 95% CI 13.37-25.46), and heparan sulfate NS+NS2S+NS6S (MD 67.00; 95% CI 31.00-103.00) in patients with SAE compared to the patients with sepsis alone.ConclusionPlasma glycocalyx-associated molecules are elevated in SAE and may be useful for early identification of cognitive decline in sepsis patients

Data from: Comparison of methodological quality of positive versus negative comparative studies published in Indian medical journals: a systematic review

Objectives: Published negative studies should have the same rigour of methodological quality as studies with positive findings. However, the methodological quality of negative versus positive studies is not known. The objective was to assess the reported methodological quality of positive versus negative studies published in Indian medical journals. Design: A systematic review (SR) was performed of all comparative studies published in Indian medical journals with a clinical science focus and impact factor >1 between 2011 and 2013. The methodological quality of randomised controlled trials (RCTs) was assessed using the Cochrane risk of bias tool, and the Newcastle-Ottawa scale for observational studies. The results were considered positive if the primary outcome was statistically significant and negative otherwise. When the primary outcome was not specified, we used data on the first outcome reported in the history followed by the results section. Differences in various methodological quality domains between positive versus negative studies were assessed by Fisher's exact test. Results: Seven journals with 259 comparative studies were included in this SR. 24% (63/259) were RCTs, 24% (63/259) cohort studies, and 49% (128/259) case–control studies. 53% (137/259) of studies explicitly reported the primary outcome. Five studies did not report sufficient data to enable us to determine if results were positive or negative. Statistical significance was determined by p value in 78.3% (199/254), CI in 2.8% (7/254), both p value and CI in 11.8% (30/254), and only descriptive in 6.3% (16/254) of studies. The overall methodological quality was poor and no statistically significant differences between reporting of methodological quality were detected between studies with positive versus negative findings. Conclusions: There was no difference in the reported methodological quality of positive versus negative studies. However, the uneven reporting of positive versus negative studies (72% vs 28%) indicates a publication bias in Indian medical journals with an impact factor of >1

Comparing Trends and Outcomes among HIV-Infected vs. HIV Uninfected Patients with Tuberculosis: A 5-Year Experience Within the Florida Department of Health in Hillsborough County

Background: Although the rate of tuberculosis (TB) has significantly declined in the United States, elimination has plateaued. Florida is one of the states with the greatest number of cases. The majority of cases occur in foreign-born individuals. Human immunodeficiency virus (HIV) is also a major contributor. HIV-TB coinfection leads to reciprocal interactions with significant clinical impact. We aim to compare the risk factors, clinical findings, and outcomes among HIV-infected vs. HIV uninfected patients. Methods: A retrospective cohort study of TB cases over a 5 year period (2012–2017) was conducted. All patients with HIV co-infection with age- and gender-matched HIV negative controls were included. The diagnosis of TB was made via clinical, microbiological, radiological, and/or PCR based methods. SPSS was used for statistical data analysis. Results: A total of 411 TB cases were identified and 66 patients (33 HIV-infected plus 33 HIV un-infected) were eligible for inclusion. The median age was 49 years (range 22–70). The male to female ratio was 21:12 and 50% of patients had TB symptoms; the rest had abnormal imaging or lab finding. Cases were confirmed via positive sputum smear, culture, or PCR (Figures 1–3). Only 11 patients were lost to follow-up, thus 83.3% completed therapy. A total of 5 persons died (Table 1). Conclusion: The rate of HIV-TB coinfection in the United States was 5.3% in 2018; higher among injection drugs users, homeless persons, inmates, and alcoholics. In our study, the rate of HIV-TB coinfection was slightly higher (8%). The difference was not statistically significant in regards to foreign born, homelessness, and incarceration. Only 3 patients admitted to injection drug use and 9 used alcohol (all HIV negative). Traditionally, HIV-TB coinfected patients have extra-pulmonary TB with higher rates of negative sputum and are at increased risk of death. In our cohort, the difference was statistically significant (P = 0.009) only for cavitary TB (predominated in HIV un-infected) but no difference in outcomes was observed between the two groups. These findings suggest changing trends in HIV-TB coinfection which may be partly related to our setting and demographics but may be attributed to better access to care and antiretroviral therapy at large

Comparing Trends and Outcomes among HIV-Infected vs. HIV Uninfected Patients with Tuberculosis: A 5-Year Experience Within the Florida Department of Health in Hillsborough County

Background: Although the rate of tuberculosis (TB) has significantly declined in the United States, elimination has plateaued. Florida is one of the states with the greatest number of cases. The majority of cases occur in foreign-born individuals. Human immunodeficiency virus (HIV) is also a major contributor. HIV-TB coinfection leads to reciprocal interactions with significant clinical impact. We aim to compare the risk factors, clinical findings, and outcomes among HIV-infected vs. HIV uninfected patients. Methods: A retrospective cohort study of TB cases over a 5 year period (2012–2017) was conducted. All patients with HIV co-infection with age- and gender-matched HIV negative controls were included. The diagnosis of TB was made via clinical, microbiological, radiological, and/or PCR based methods. SPSS was used for statistical data analysis. Results: A total of 411 TB cases were identified and 66 patients (33 HIV-infected plus 33 HIV un-infected) were eligible for inclusion. The median age was 49 years (range 22–70). The male to female ratio was 21:12 and 50% of patients had TB symptoms; the rest had abnormal imaging or lab finding. Cases were confirmed via positive sputum smear, culture, or PCR (Figures 1–3). Only 11 patients were lost to follow-up, thus 83.3% completed therapy. A total of 5 persons died (Table 1). Conclusion: The rate of HIV-TB coinfection in the United States was 5.3% in 2018; higher among injection drugs users, homeless persons, inmates, and alcoholics. In our study, the rate of HIV-TB coinfection was slightly higher (8%). The difference was not statistically significant in regards to foreign born, homelessness, and incarceration. Only 3 patients admitted to injection drug use and 9 used alcohol (all HIV negative). Traditionally, HIV-TB coinfected patients have extra-pulmonary TB with higher rates of negative sputum and are at increased risk of death. In our cohort, the difference was statistically significant (P = 0.009) only for cavitary TB (predominated in HIV un-infected) but no difference in outcomes was observed between the two groups. These findings suggest changing trends in HIV-TB coinfection which may be partly related to our setting and demographics but may be attributed to better access to care and antiretroviral therapy at large