Prevention, Diagnosis, and Management of Chronic Wounds in Older Adults.

Chronic wounds are common, disproportionately affect older adults, and are likely to be encountered by providers across all specialties and care settings. All providers should be familiar with basic wound prevention, identification, classification, and treatment approach, all of which are outlined in this article.

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

BACKGROUND: Immune-related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti-programmed cell death protein 1 (PD-1) therapy. MATERIALS AND METHODS: All patients with metastatic melanoma and non-small cell lung cancer (NSCLC) treated with anti-PD-1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan-Meier method and log-rank test was used for time-to-event analysis. RESULTS: In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression-free-survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. CONCLUSION: Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. IMPLICATIONS FOR PRACTICE: The results of this study suggest that women may be at a higher risk for immune-related adverse events (irAEs) compared with men when treated with anti-programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow-up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment-related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.

Prognostic risk model for patients with high-risk polycythemia vera and essential thrombocythemia.

INTRODUCTION: Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are the most frequent Philadelphia chromosome-negative myeloproliferative neoplasms, the other entity being myelofibrosis. Management of patients with PV and ET is fraught with difficulties as they have an inherent tendency to cause thrombotic and hemorrhagic events. There are no curative treatment options, therefore it is important that a risk-adapted treatment approach is applied. Areas covered: This review discusses existing literature about prognosis in PV and ET, and addresses critical aspects related to defining 'high-risk' disease. In addition to the traditional risk factors such as age and prior thrombotic history, we discuss the prognostic impact of additional parameters such as cardiovascular risk factors, white blood cell count, karyotype and gene mutations. Expert commentary: We use age>60 years, presence of JAK2 mutation and a prior thrombotic history as the principle determinants of 'high-risk' for thrombosis in PV and ET, dividing the patients into very-low, low, intermediate and high-risk disease. Typically, low-risk patients are treated either with observation or aspirin alone. High-risk patients require cytoreductive therapies, along with aspirin and/or systemic anticoagulation. Intermediate-risk patients are treated on a case-by-case basis. Further, we aim to maintain a hematocrit <45% with aggressive phlebotomy in patients with PV.

Targeted next generation sequencing and identification of risk factors in World Health Organization defined atypical chronic myeloid leukemia.

Atypical chronic myeloid leukemia (aCML) is an aggressive myeloid neoplasm with overlapping features of myelodysplastic syndromes (prominent granulocytic dysplasia) and myeloproliferative neoplasms (neutrophilic leukocytosis). We studied 25 molecularly-annotated and World Health Organization defined aCML patients; median age 70 years, 84% males. Cytogenetic abnormalities were seen in 36% and gene mutations in 100%. Mutational frequencies were, ASXL1 28%, TET2 16%, NRAS 16%, SETBP1 12%, RUNX1 12%, ETNK1 8%, and PTPN11 4%. Fifteen patients (60%) had >1 mutation, while 9 (36%) had ≥3. The median overall survival (OS) was 10.8 months and at last follow up (median 11 months), 17 (68%) deaths and 2 (8%) leukemic transformations were documented. On univariate analysis, survival was adversely impacted by advanced age (P = .02), low hemoglobin (P = .01), red blood cell transfusion dependence (P = .03), high white blood cell count (P = .02), TET2 (P = .03), NRAS (P = .04), PTPN11 (P = .02) mutations and the presence of ≥3 gene mutations (P = .006); ASXL1, SETBP1, and ETNK1 mutations did not impact OS. In multivariable analysis, advanced age (P = .003) [age >67: HR 10.1, 95% CI 1.3-119], low hemoglobin (P = .008) [HB< 10 gm/dL: HR 8.2, 95% CI 1.6-23.2] and TET2 mutations (P = .01) [HR 8.8, 95% CI 1.6-47.7] retained prognostic significance. We then used age >67 years, hemoglobin <10 gm/dL and the presence of TET2 mutations (each counted as one risk factor) to create a hazard ratio weighted prognostic model; effectively stratifying patients into two risk categories, low (0-1 risk factor) and high (≥2 risk factors), with median OS of 18 and 7 months, respectively.