Cytoreductive therapy in younger adults with polycythemia vera: a meta-analysis of safety and outcomes.

ABSTRACT: Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.

In patients with chronic heart failure which polypharmacy pheno-groups are associated with adverse health outcomes? (Polypharmacy pheno-groups and heart failure outcomes).

BACKGROUND: Patients with heart failure are living longer with the inevitable morbidity of rising medication counts. It remains uncertain what fraction of this ensuing polypharmacy exactly predicts adverse clinical outcomes. METHODS: This prospective study examined records of patients admitted to a Weill Cornell-affiliated tertiary medical institution with a confirmed diagnosis of heart failure between January 2018 to January 2022. Each patient's medications for the past four months were tallied, and a definitional threshold of ≤4, ≥5, ≥10 medications was established. The primary outcome was all-cause mortality within the study period. RESULTS: Out of a total of 7354 patients included in the study, 70 % were males with a median age of 59 years IQR (48-71). The median (IQR) age-adjusted Charlson Comorbidity Index (CCI) was 21-5. A total of 1475 (20 %) participants died within the study period. Patient cohorts with excessive polypharmacy (≥9 medications) had the highest probability of survival up to 1.6 years compared to those with lower medication thresholds (≤4); the mortality rate decreased by 18 % for patients with excessive polypharmacy [HR = 0.82, 95 % CI: 0.71-0.94]). Conversely, patients with non-heart failure-related polypharmacy had increased risks of ICU admissions (aOR = 1.78, 95 % CI: 1.13-2.70). CONCLUSION: In an examination of a database of patients with chronic heart failure, major non-heart failure-related polypharmacy was associated with increased risks in intensive care admissions. Excessive polypharmacy was associated with increased rates of survival.

Effectiveness of the pre-Omicron COVID-19 vaccines against Omicron in reducing infection, hospitalization, severity, and mortality compared to Delta and other variants: A systematic review.

Despite widespread mass rollout programs, the rapid spread of the SARS-CoV-2 Omicron variant called into question the effectiveness of the existing vaccines against infection, hospitalization, severity, and mortality compared to previous variants. This systematic review summarizes and compares the effectiveness of the COVID-19 vaccines, with respect to the above outcomes in adults, children, and adolescents. A comprehensive literature search was undertaken on several databases. Only 51 studies met our inclusion criteria, revealing that the protection from primary vaccination against Omicron infection is inferior to protection against Delta and Alpha infections and wanes faster over time. However, mRNA vaccine boosters were reported to reestablish effectiveness, although to a lower extent against Omicron. Nonetheless, primary vaccination was shown to preserve strong protection against Omicron-associated hospitalization, severity, and death, even months after last dose. However, boosters provide more robust and longer-lasting protection against hospitalizations due to Omicron as compared to only primary series.

Penetrance of male breast cancer susceptibility genes: a systematic review.

PURPOSE: Several male breast cancer (MBC) susceptibility genes have been identified, but the MBC risk for individuals with a pathogenic variant in each of these genes (i.e., penetrance) remains unclear. We conducted a systematic review of studies reporting the penetrance of MBC susceptibility genes to better summarize current estimates of penetrance. METHODS: A search query was developed to identify MBC-related papers indexed in PubMed/MEDLINE. A validated natural language processing method was applied to identify papers reporting penetrance estimates. These penetrance studies' bibliographies were reviewed to ensure comprehensiveness. We accessed the potential ascertainment bias for each enrolled study. RESULTS: Fifteen penetrance studies were identified from 12,182 abstracts, covering five purported MBC susceptibility genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2. Cohort (n = 6, 40%) and case-control (n = 5, 33%) studies were the two most common study designs, followed by family-based (n = 3, 20%), and a kin-cohort study (n = 1, 7%). Seven of the 15 studies (47%) adjusted for ascertainment adequately and therefore the MBC risks reported by these seven studies can be considered applicable to the general population. Based on these seven studies, we found pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 show an increased risk for MBC. The association between BRCA1 and MBC was not statistically significant. CONCLUSION: This work supports the conclusion that pathogenic variants in ATM, BRCA2, CHEK2 c.1100delC, and PALB2 increase the risk of MBC, whereas pathogenic variants in BRCA1 may not be associated with increased MBC risk.

Pregnancy and Neonatal Outcomes in SARS-CoV-2 Infection: A Systematic Review.

With the emergence of SARS-CoV-2 and its rapid spread, concerns regarding its effects on pregnancy outcomes have been growing. We reviewed 245 pregnancies complicated by maternal SARS-CoV-2 infection across 48 studies listed on PubMed and MedRxiv. The most common clinical presentations were fever (55.9%), cough (36.3%), fatigue (11.4%), and dyspnea (12.7%). Only 4.1% of patients developed respiratory distress. Of all patients, 89.0% delivered via cesarean section (n = 201), with a 33.3% rate of gestational complications, a 35.3% rate of preterm delivery, and a concerning 2.5% rate of stillbirth delivery or neonatal death. Among those tested, 6.45% of newborns were reported positive for SARS-CoV-2 infection. Relative to known viral infections, the prognosis for pregnant women with SARS-CoV-2 is good, even in the absence of specific antiviral treatment. However, neonates and acute patients, especially those with gestational or preexisting comorbidities, must be actively managed to prevent the severe outcomes being increasingly reported in the literature.