Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting.

The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up.

We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5).

Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia.

gov, NCT02384122.

The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products.

MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.6.

After 330 participants were randomized, a planned interim analysis of 297 participants (145 MIRASOL, 152 CONTROL) receiving ≥1 study transfusion found a 2.79-relative rate (RR) in the MIRASOL compared to the CONTROL in number of days with ≥Grade 2 bleeding (95% confidence interval [CI] 1.67-4.67). The proportion of subjects with ≥Grade 2 bleeding was 40.0% (n = 58) in MIRASOL and 30.3% (n = 46) in CONTROL (RR = 1.32, 95% CI 0.97-1.81, p = .08). Corrected count increments were lower (p < .01) and the number of PLT transfusion episodes per participant was higher (RR = 1.22, 95% CI 1.05-1.41) in MIRASOL. There was no difference in the days of PLT support (hazard ratio = 0.86, 95% CI 0.68-1.08) or total number of red blood cell transfusions (RR = 1.12, 95% CI 0.91-1.37) between MIRASOL versus CONTROL. Transfusion emergent adverse events were reported in 119 MIRASOL participants (84.4%) compared to 133 (82.6%) participants in CONTROL (p = NS).

This study did not support that MIRASOL was non-inferior compared to conventional platelets using the novel endpoint number of days with ≥Grade 2 bleeding in MIRASOL when compared to CONTROL.

Guidelines recommend that intravenous iron should be considered to improve symptoms of heart failure (HF) and reduce the risk for HF admissions in patients after acute HF.

This study sought to analyze the effect of intravenous iron on cardiovascular (CV) death and HF admissions in a broad population of HF patients with iron deficiency and the relation with baseline transferrin saturation (TSAT).

A systematic review of all published randomized controlled trials assessing the effect of intravenous iron in patients with iron deficiency and HF between January 1, 2000, and August 26, 2023, was performed. The overall treatment effect was estimated using a fixed effect model for: 1) CV death; 2) CV death and HF admission; 3) first HF admission; and 4) total HF admissions. Metaregression through a mixed effect model was used to explore the impact of baseline TSAT in case of heterogeneity among trial results.

A total of 14 randomized controlled trials were identified in the systematic review and retained in the meta-analysis. Aggregate-level data were included on 6,624 HF patients, 3,407 of whom were randomized to intravenous iron and 3,217 to placebo. Treatment with intravenous iron resulted in a lower risk for CV death (OR: 0.867 [95% CI: 0.755-0.955]; P = 0.0427), combined CV death and HF admission (OR: 0.838 [95% CI: 0.751-0.936]; P = 0.0015), first HF admission (OR: 0.855 [95% CI: 0.744-0.983]; P = 0.0281), and total HF admissions (rate ratio: 0.739 [95% CI: 0.661-0.827]; P < 0.0001). Significant heterogeneity among trial results was observed for first and total HF admissions. Metaregression suggested that some of the heterogeneity was related to the baseline TSAT of the enrolled population, with trials enrolling patients with lower TSAT exhibiting a large effect size on HF-related events.

The totality of data suggests that treatment with intravenous iron reduces both CV death and HF-related events in a broad population with HF. A lower baseline TSAT might be important for the effect on HF-related events.

Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings.

We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis.

NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (β=-27.6, 95% CI (-51.3 to -3.9), p=0.02).

Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity.

Level II.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive or relapsing weakness and numbness of the limbs, which lasts for at least two months. Uncontrolled studies have suggested that intravenous immunoglobulin (IVIg) could help to reduce symptoms. This is an update of a review first published in 2002 and last updated in 2013.

To assess the efficacy and safety of intravenous immunoglobulin in people with chronic inflammatory demyelinating polyradiculoneuropathy.

We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers on 8 March 2023.

We selected randomised controlled trials (RCTs) and quasi-RCTs that tested any dose of IVIg versus placebo, plasma exchange, or corticosteroids in people with definite or probable CIDP.

We used standard Cochrane methods. Our primary outcome was significant improvement in disability within six weeks after the start of treatment, as determined and defined by the study authors. Our secondary outcomes were change in mean disability score within six weeks, change in muscle strength (Medical Research Council (MRC) sum score) within six weeks, change in mean disability score at 24 weeks or later, frequency of serious adverse events, and frequency of any adverse events. We used GRADE to assess the certainty of evidence for our main outcomes.

We included nine RCTs with 372 participants (235 male) from Europe, North America, South America, and Israel. There was low statistical heterogeneity between the trial results, and the overall risk of bias was low for all trials that contributed data to the analysis. Five trials (235 participants) compared IVIg with placebo, one trial (20 participants) compared IVIg with plasma exchange, two trials (72 participants) compared IVIg with prednisolone, and one trial (45 participants) compared IVIg with intravenous methylprednisolone (IVMP). We included one new trial in this update, though it contributed no data to any meta-analyses. IVIg compared with placebo increases the probability of significant improvement in disability within six weeks of the start of treatment (risk ratio (RR) 2.40, 95% confidence interval (CI) 1.72 to 3.36; number needed to treat for an additional beneficial outcome (NNTB) 4, 95% CI 3 to 5; 5 trials, 269 participants; high-certainty evidence). Since each trial used a different disability scale and definition of significant improvement, we were unable to evaluate the clinical relevance of the pooled effect. IVIg compared with placebo improves disability measured on the Rankin scale (0 to 6, lower is better) two to six weeks after the start of treatment (mean difference (MD) -0.26 points, 95% CI -0.48 to -0.05; 3 trials, 90 participants; high-certainty evidence). IVIg compared with placebo probably improves disability measured on the Inflammatory Neuropathy Cause and Treatment (INCAT) scale (1 to 10, lower is better) after 24 weeks (MD 0.80 points, 95% CI 0.23 to 1.37; 1 trial, 117 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and placebo in the frequency of serious adverse events (RR 0.82, 95% CI 0.36 to 1.87; 3 trials, 315 participants; moderate-certainty evidence). The trial comparing IVIg with plasma exchange reported none of our main outcomes. IVIg compared with prednisolone probably has little or no effect on the probability of significant improvement in disability four weeks after the start of treatment (RR 0.91, 95% CI 0.50 to 1.68; 1 trial, 29 participants; moderate-certainty evidence), and little or no effect on change in mean disability measured on the Rankin scale (MD 0.21 points, 95% CI -0.19 to 0.61; 1 trial, 24 participants; moderate-certainty evidence). There is probably little or no difference between IVIg and prednisolone in the frequency of serious adverse events (RR 0.45, 95% CI 0.04 to 4.69; 1 cross-over trial, 32 participants; moderate-certainty evidence). IVIg compared with IVMP probably increases the likelihood of significant improvement in disability two weeks after starting treatment (RR 1.46, 95% CI 0.40 to 5.38; 1 trial, 45 participants; moderate-certainty evidence). IVIg compared with IVMP probably has little or no effect on change in disability measured on the Rankin scale two weeks after the start of treatment (MD 0.24 points, 95% CI -0.15 to 0.63; 1 trial, 45 participants; moderate-certainty evidence) or on change in mean disability measured with the Overall Neuropathy Limitation Scale (ONLS, 1 to 12, lower is better) 24 weeks after the start of treatment (MD 0.03 points, 95% CI -0.91 to 0.97; 1 trial, 45 participants; moderate-certainty evidence). The frequency of serious adverse events may be higher with IVIg compared with IVMP (RR 4.40, 95% CI 0.22 to 86.78; 1 trial, 45 participants, moderate-certainty evidence).

Evidence from RCTs shows that IVIg improves disability for at least two to six weeks compared with placebo, with an NNTB of 4. During this period, IVIg probably has similar efficacy to oral prednisolone and IVMP. Further placebo-controlled trials are unlikely to change these conclusions. In one large trial, the benefit of IVIg compared with placebo in terms of improved disability score persisted for 24 weeks. Further research is needed to assess the long-term benefits and harms of IVIg relative to other treatments.

Diffuse alveolar hemorrhage (DAH) is a life-threatening manifestation of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The Plasma Exchange (PLEX) and Glucocorticoids (GC) in Severe AAV (PEXIVAS;NCT00987389) trial was the largest in AAV and first to enroll participants with DAH requiring mechanical ventilation.

Evaluate characteristics, treatment effects, outcomes for patients with AAV with and without DAH.

PEXIVAS randomized 704 participants to PLEX or no-PLEX and reduced or standard-dose GC. DAH status was defined at enrollment as no-DAH, non-severe, or severe (room air SpO2≤85% or use of mechanical ventilation).

At enrollment, 191(27.1%) participants had DAH (61 severe, including 29 ventilated) and were younger, more frequently relapsing, PR3-ANCA positive, and had lower serum creatinine but were more frequently dialyzed than participants without DAH (n=513,72.9%). Among those with DAH, 8/95(8.4%) receiving PLEX died within one year vs. 15/96(15.6%) with no-PLEX (HR 0.52,CI 0.21-1.24), while 13/96(13.5%) receiving reduced-GC died vs. 10/95(10.5%) with standard-GC (HR 1.33,CI 0.57-3.13). When ventilated, ventilator-free days were similar with PLEX vs. no-PLEX (medians 25,IQR 22-26 vs. 22-27), fewer with reduced-GC (23[20-25]) vs. standard-GC (26[25-28]). Treatment effects on mortality did not vary by presence or severity of DAH. Overall, 23/191(12.0%) with DAH died within one year vs. 34/513(6.6%) without DAH. End-stage kidney disease and serious infections did not differ by DAH status or treatments.

Patients with AAV and DAH differ from those without DAH in multiple ways. Further data are required to confirm or refute a benefit of PLEX or GC dosing on mortality. Clinical trial registration available at www.

gov, ID: NCT00987389.

Pyruvate kinase (PK) deficiency is a rare, hereditary disease characterized by chronic hemolytic anemia. Iron overload is a common complication regardless of age, genotype, or transfusion history. Mitapivat, an oral, allosteric PK activator, improves anemia and hemolysis in adult patients with PK deficiency. Mitapivat's impact on iron overload and ineffective erythropoiesis was evaluated in adults with PK deficiency who were not regularly transfused in the phase 3 ACTIVATE trial and long-term extension (LTE) (NCT03548220/NCT03853798). Patients in the LTE received mitapivat throughout ACTIVATE/LTE (baseline to Week [W] 96; mitapivat-to-mitapivat [M/M] arm) or switched from placebo (baseline to W24) to mitapivat (W24 to 96; placebo-to-mitapivat [P/M] arm). Changes from baseline in markers of iron overload and erythropoiesis were assessed to W96. Improvements in hepcidin (mean [95% confidence interval ⟨CI ⟩] 4770.0 ng/L [-1532.3, 11,072.3], erythroferrone (-9834.9 ng/L [-14,328.4, -5341.3]), soluble transferrin receptor (-56.0 nmol/L [-84.8, -27.2]), and erythropoietin (-32.85 IU/L [-54.65, -11.06]) were observed in the M/M arm (n=40) from baseline to W24, sustained to W96. No improvements were observed in the P/M arm (n=40) to W24; however, upon transitioning to mitapivat, improvements similar to the M/M arm were seen. Mean (95% CI) changes from baseline in liver iron concentration (LIC) by magnetic resonance imaging (MRI) at W96 were -2.0 mg Fe/g dry weight (dw) (-4.8, -0.8; M/M arm) and -1.8 mg Fe/g dw (-4.4, 0.80; P/M arm). Mitapivat is the first disease-modifying pharmacotherapy shown to have beneficial effects on iron overload and ineffective erythropoiesis in patients with PK deficiency.

Care bundles are a promising approach to reducing postpartum hemorrhage-related morbidity and mortality. We assessed the effectiveness and safety of care bundles for postpartum hemorrhage prevention and/or treatment.

We searched MEDLINE, Embase, Cochrane CENTRAL, Maternity and Infant Care Database, and Global Index Medicus (inception to June 9, 2023) and ClinicalTrials.gov and the International Clinical Trials Registry Platform (last 5 years) using a phased search strategy, combining terms for postpartum hemorrhage and care bundles.

Peer-reviewed studies evaluating postpartum hemorrhage-related care bundles were included. Care bundles were defined as interventions comprising ≥3 components implemented collectively, concurrently, or in rapid succession. Randomized and nonrandomized controlled trials, interrupted time series, and before-after studies (controlled or uncontrolled) were eligible.

Risk of bias was assessed using RoB 2 (randomized trials) and ROBINS-I (nonrandomized studies). For controlled studies, we reported risk ratios for dichotomous outcomes and mean differences for continuous outcomes, with certainty of evidence determined using GRADE. For uncontrolled studies, we used effect direction tables and summarized results narratively.

Twenty-two studies were included for analysis. For prevention-only bundles (2 studies), low-certainty evidence suggests possible benefits in reducing blood loss, duration of hospitalization, and intensive care unit stay, and maternal well-being. For treatment-only bundles (9 studies), high-certainty evidence shows that the E-MOTIVE intervention reduced risks of composite severe morbidity (risk ratio, 0.40; 95% confidence interval, 0.32-0.50) and blood transfusion for bleeding, postpartum hemorrhage, severe postpartum hemorrhage, and mean blood loss. One nonrandomized trial and 7 uncontrolled studies suggest that other postpartum hemorrhage treatment bundles might reduce blood loss and severe postpartum hemorrhage, but this is uncertain. For combined prevention/treatment bundles (11 studies), low-certainty evidence shows that the California Maternal Quality Care Collaborative care bundle may reduce severe maternal morbidity (risk ratio, 0.64; 95% confidence interval, 0.57-0.72). Ten uncontrolled studies variably showed possible benefits, no effects, or harms for other bundle types. Nearly all uncontrolled studies did not use suitable statistical methods for single-group pretest-posttest comparisons and should thus be interpreted with caution.

The E-MOTIVE intervention improves postpartum hemorrhage-related outcomes among women delivering vaginally, and the California Maternal Quality Care Collaborative bundle may reduce severe maternal morbidity. Other bundle designs warrant further effectiveness research before implementation is contemplated.

The use of platelet-rich plasma (PRP) in orthopaedics continues to increase. One common use of PRP is as an adjunct in rotator cuff repair surgery. Multiple systematic reviews and meta-analyses have summarized the data on PRP use in rotator cuff repair surgery. However, systematic reviews and meta-analyses are subject to spin bias, where authors' interpretations of results influence readers' interpretations.

To evaluate spin in the abstracts of systematic reviews and meta-analyses of PRP with rotator cuff repair surgery.

Systematic review; Level of evidence, 3.

A PubMed and Embase search was conducted using the terms rotator cuff repair and PRP and systematic review or meta-analysis. After review of 74 initial studies, 25 studies met the inclusion criteria. Study characteristics were documented, and each study was evaluated for the 15 most common forms of spin and using the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews, Version 2) rating system. Correlations between spin types and study characteristics were evaluated using binary logistic regression for continuous independent variables and a chi-square test or Fisher exact test for categorical variables.

At least 1 form of spin was found in 56% (14/25) of the included studies. In regard to the 3 different categories of spin, a form of misleading interpretation was found in 56% (14/25) of the studies. A form of misleading reporting was found in 48% (12/25) of the studies. A form of inappropriate extrapolation was found in 16% (4/25) of the studies. A significant association was found between misleading interpretation and publication year (odds ratio [OR], 1.41 per year increase in publication; 95% CI, 1.04-1.92; P = .029) and misleading reporting and publication year (OR, 1.41 per year increase in publication; 95% CI, 1.02-1.95; P = .037). An association was found between inappropriate extrapolation and journal impact factor (OR, 0.21 per unit increase in impact factor; 95% CI, 0.044-0.99; P = .048).

A significant amount of spin was found in the abstracts of systematic reviews and meta-analyses of PRP use in rotator cuff repair surgery. Given the increasing use of PRP by clinicians and interest among patients, spin found in these studies may have a significant effect on clinical practice.