The prognostic utility of protein C as a biomarker for adult sepsis: a systematic review and meta-analysis

Background Sepsis, the dysregulated host response to infection, triggers abnormal pro-coagulant and pro-inflammatory host responses. Limitations in early disease intervention highlight the need for effective diagnostic and prognostic biomarkers. Protein C’s role as an anticoagulant and anti-inflammatory molecule makes it an appealing target for sepsis biomarker studies. This meta-analysis aims to assess the diagnostic and prognostic value of protein C (PC) as a biomarker for adult sepsis. Methods We searched MEDLINE, PubMed, EMBASE, CINAHL and Cochrane Library from database inception to September 12, 2021. We included prospective observational studies of (1) adult patients (> 17) with sepsis or suspicion of sepsis that; (2) measured PC levels with 24 h of study admission with; and (3) the goal of examining PC as a diagnostic or prognostic biomarker. Two authors screened articles and conducted risk of bias (RoB) assessment, using the Quality in Prognosis Studies (QUIPS) and the Quality Assessment in Diagnostic Studies-2 (QUADAS-2) tools. If sufficient data were available, meta-analysis was conducted to estimate the standardized mean difference (SMD) between patient populations. Results Twelve studies were included, and 8 were synthesized for meta-analysis. Pooled analysis demonstrated moderate certainty of evidence that PC levels were less reduced in sepsis survivors compared to non-survivors (6 studies, 741 patients, SMD = 0.52, 95% CI 0.24–0.81, p = 0.0003, I2 = 55%), and low certainty of evidence that PC levels were less reduced in septic patients without disseminated intravascular coagulation (DIC) compared to those with DIC (3 studies, 644 patients, SMD = 0.97, 95% CI 0.62–1.32, p < 0.00001, I2 = 67%). PC could not be evaluated as a diagnostic tool due to heterogeneous control populations between studies. Conclusion and relevance Our review demonstrates that PC levels were significantly higher in sepsis survivors compared to non-survivors and patients with sepsis but not disseminated intravascular coagulation (DIC). Our evaluation is limited by high RoB in included studies and poor reporting of the sensitivity and specificity of PC as a sepsis biomarker. Future studies are needed to determine the sensitivity and specificity of PC to identify its clinical significance as a biomarker for early sepsis recognition. Trial Registration PROSPERO registration number: CRD42021229786. The study protocol was published in BMJ Open.

Muscle hypertrophy and strength gains after resistance training with different volume matched loads: a systematic review and meta-analysis.

The purpose of this paper was to conduct a systematic review and meta-analysis of studies that compared muscle hypertrophy and strength gains between resistance training protocols employing very low (VLL<30% of 1RM or >35 RM), low (LL30%-59% of 1RM, or 16–35 RM), moderate (ML60%-79% of 1RM, or 8 -15RM) and high load (HL≥80% of 1RM, or ≤7 RM) with matched volume loads (sets x reps x weight). A pooled analysis of the standardized mean difference for 1RM strength outcomes across the studies showed a benefit favoring HL vs. LL and vs. ML; and favoring ML vs. LL. Results from LL and VLL indicated little difference. A pooled analysis of the standardized mean difference for hypertrophy outcomes across all studies showed no differences between the training loads. Our findings indicate that, when volume load is equated between conditions, the highest loads induce superior dynamic strength gains. Alternatively, hypertrophic adaptations are similar irrespective of the magnitude of load. NOVELTY BULLETS: • Training with higher loads elicits greater gains in 1RM muscle strength when compared to lower loads, even when volume load is equated between conditions. • Muscle hypertrophy is similar irrespective of the magnitude of load, even when volume load is equated between conditions.

Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials

Background and Objectives:Detailed study of tenecteplase (TNK) in patients greater than 80 years of age is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients greater than 80 years with large vessel occlusion.Methods:A pooled analysis of the EXTEND-IA TNK randomized controlled trials (n=502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25mg/kg, TNK 0.40mg/kg, and alteplase 0.90mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin scale (mRS), all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIHSS, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models.Results:In patients >80 years (n=137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, adjusted common OR=2.70, 95% CI: 1.23-5.94) and reduced mortality (aOR=0.34, 95% CI: 0.13-0.91) versus 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs. 4, acOR=2.28, 95% CI: 1.03-5.05) versus alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, one patient treated with alteplase and zero patients treated with TNK 0.25 mg/kg. In patients ≤ 80 years, no differences in 90-day mRS, mortality, or symptomatic ICH was observed between TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg.Conclusions:TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients greater than 80 years of age. No differences between the doses were observed in younger patients.Classification of Evidence:This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.Trial Registration:ClinicalTrials.gov Identifiers: NCT02388061, NCT03340493https://www.clinicaltrials.gov/ct2/show/NCT02388061https://www.clinicaltrials.gov/ct2/show/NCT03340493

Tumor infiltrating lymphocyte stratification of prognostic staging of early-stage triple negative breast cancer

The importance of integrating biomarkers into the TNM staging has been emphasized in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging system. In a pooled analysis of 2148 TNBC-patients in the adjuvant setting, TILs are found to strongly up and downstage traditional pathological-staging in the Pathological and Clinical Prognostic Stage Groups from the AJJC 8th edition Cancer Staging System. This suggest that clinical and research studies on TNBC should take TILs into account in addition to stage, as for example patients with stage II TNBC and high TILs have a better outcome than patients with stage I and low TILs.

Complication Differences Between the Tumescent and Non-Tumescent Dissection Techniques for Mastectomy: A Meta-Analysis

PurposeWe conducted a systematic literature search and pooled data from studies to compare the incidence of complications between the tumescent and non-tumescent techniques for mastectomy.MethodsWe searched PubMed, Embase, BioMed Central, Ovid, and CENTRAL databases for studies comparing the two mastectomy techniques up to November 1st, 2020. We used a random-effects model to calculate odds ratios (OR) with 95% confidence intervals (CI).ResultsNine studies were included with one randomized controlled trial (RCT). Meta-analysis indicated no statistically significant difference in the incidence of total skin necrosis (OR 1.18 95% CI 0.71, 1.98 I2 = 82% p=0.52), major skin necrosis (OR 1.58 95% CI 0.69, 3.62 I2 = 71% p=0.28), minor skin necrosis (OR 1.11 95% CI 0.43, 2.85 I2 = 72% p=0.83), hematoma (OR 1.19 95% CI 0.80, 1.79 I2 = 4% p=0.39), and infections (OR 0.87 95% CI 0.54, 1.40 I2 = 54% p=0.56) between tumescent and non-tumescent groups. Analysis of studies using immediate alloplastic reconstruction revealed no statistically significant difference in the incidence of explantation between the two groups (OR 0.78 95% CI 0.46, 1.34 I2 = 62% p=0.37). Multivariable-adjusted ORs on total skin necrosis were available from three studies. Pooled analysis indicated no statistically significant difference between tumescent and non-tumescent groups (OR 1.72 95% CI 0.72, 4.13 I2 = 87% p=0.23).ConclusionLow-quality evidence derived mostly from non-randomized studies is indicative of no difference in the incidence of skin necrosis, hematoma, seroma, infection, and explantation between the tumescent and non-tumescent techniques of mastectomy. There is a need for high-quality RCTs to further strengthen the evidence.

Evaluation of tranexamic acid after total hip arthroplasty over 60 years old in China: a Systematic Review and Meta-analysis

Review question / Objective: The purpose of this meta-analysis was to evaluate the efficacy of tranexamic acid after total hip arthroplasty in patients older than 60 years old in China by meta-analysis. Participant or population: All trials included in our study meet the following criteria: (1) All studies were original RCTs; (2) The mean age of patients for each study was ≥ 60 years old; (3) Patients were received total hip arthroplasty in all studies; (4) All studies included oral and iv or topical groups, with a comparison of outcomes between the two groups; (5) The full text of the included literature can be obtained, and the measurement data of hemoglobin drop, total blood loss, transfusion rate, complication, length of stay can be extracted. The following studies were excluded from the meta-analysis: nonrandomized studies; the patients with age<60; studies not suitable with the inclusive criteria; and articles for which we were unable to obtain the full text and relevant data for pooled analysis.

The Efficacy of Denosumab in Patients With Rheumatoid Arthritis: A Systematic Review and Pooled Analysis of Randomized or Matched Data

ObjectiveThe purpose of this study was to evaluate the efficacy of denosumab treatment in patients with rheumatoid arthritis (RA).MethodsThe Medline, Embase and Cochrane Library databases were searched for relevant clinical studies. Studies that assessed the efficacy of denosumab in patients with RA were identified. The primary endpoints were the percent changes in bone mineral density (BMD), and the changes in modified total Sharp score (mTSS), modified Sharp erosion score and joint space narrowing (JSN) score. Pooled analyses were calculated using random-effect models.ResultsAfter searching the literature and performing further detailed assessments, 10 studies with a total of 1758 patients were included in the quantitative analysis. Pooled analyses showed that denosumab treatment significantly increased the percent changes in lumbar spine BMD [mean difference (MD): 5.12, confidence intervals (CI): 4.15 to 6.09], total hip BMD (MD: 2.72, 95% CI: 1.80 to 3.64) and femoral neck BMD (MD: 2.20, 95% CI: 0.94 to 3.46) compared with controls. Moreover, denosumab treatment significantly decreased the changes in mTSS (MD: -0.63, 95% CI: -0.86 to -0.41) and modified Sharp erosion score (MD: -0.62, 95% CI: -0.88 to -0.35). Subgroup analysis indicated that denosumab was superior to bisphosphonates for the improvement of BMD and the mitigation of joint destruction.ConclusionDenosumab treatment was associated with increased BMD and alleviated progression of joint destruction in RA patients, even when compared with bisphosphonates.