Citations

SummaryMyelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT‐I,) a double‐blind trial, where patients with intermediate‐2 or high‐risk MF were randomized to twice‐daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post‐polycythaemia vera, post‐essential thrombocythaemia), age (≤65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ≥2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (≥100, <100 g/l), baseline platelet count (100–200 × 109/l, >200 × 109/l), baseline palpable spleen size (≤10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan–Meier method according to original randomization group. In ruxolitinib‐treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT‐I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT‐I.

Cutaneous gamma‐delta T‐cell lymphoma (γδTCL) is a rare malignancy that typically displays an aggressive clinical course. We present an unusual case of a 57‐year‐old woman with a 3‐year history of lower extremity nodules. Histopathologic, immunophenotypic and molecular genetic studies revealed a clonal, predominantly pannicular gamma‐delta T‐cell infiltrate, leading to a diagnosis of cutaneous γδTCL. The clinical course was characterized by rapid improvement within months of starting systemic corticosteroids, with relapse in ulcerations but no new lesions more than 3 years after onset of disease. Our case and seven previously reported patients with indolent and relatively localized cutaneous γδTCL provide evidence that not all cases of this entity carry a poor prognosis. This indolent subset adds complexity to treatment of cutaneous γδTCL.

Abstract BRCA1 and BRCA2 are the most important breast and ovarian cancer susceptibility genes. Biallelic mutations in BRCA2 can lead to Fanconi anemia and predisposition to cancers, whereas biallelic BRCA1 mutations have not been confirmed, presumably because one wild-type BRCA1 allele is required during embryogenesis. This study describes an individual who was diagnosed with ovarian carcinoma at age 28 and found to have one allele with a deleterious mutation in BRCA1, c.2457delC (p.Asp821Ilefs*25), and a second allele with a variant of unknown significance in BRCA1, c.5207T&gt;C (p.Val1736Ala). Medical records revealed short stature, microcephaly, developmental delay, and significant toxicity from chemotherapy. BRCA1 p.Val1736Ala cosegregated with cancer in multiple families, associated tumors showed loss of wild-type BRCA1, and BRCA1 p.Val1736Ala showed reduced DNA damage localization. These findings represent the first validated example of biallelic deleterious human BRCA1 mutations and have implications for the interpretation of genetic test results. Significance: Accurate assessment of genetic testing data for BRCA1 mutations is essential for clinical monitoring and treatment strategies. Here, we report the first validated example of an individual with biallelic BRCA1 mutations, early-onset ovarian cancer, and clinically significant hypersensitivity to chemotherapy. Cancer Discov; 3(4); 399–405. ©2012 AACR. See related commentary by D'Andrea, p. 376 This article is highlighted in the In This Issue feature, p. 363

Mini‐AbstractWe present a case of a 25‐year‐old man with aortic regurgitation secondary to infective endocarditis. A preoperative transesophageal echocardiography demonstrated an abnormal aortic valve with possible vegetation or torn leaflet with severe aortic regurgitation, markedly dilated left coronary arteries, and a fistulous communication between the circumflex artery and the coronary sinus. The aortic valve was repaired and the coronary sinus arteriovenous fistula was ligated. At 1‐year follow‐up, there was no evidence of recurrent arteriovenous fistula or aortic regurgitation.

Objectives To quantify the occurrence of myocardial infarction ( MI ) occurring in the early postoperative period after surgical hip fracture repair and estimate the effect on 1‐year mortality. Design A population‐based, historical cohort study of individuals who underwent surgical repair of a hip fracture that used the computerized medical record linkage system of the R ochester E pidemiology P roject. Setting Academic and community hospitals, outpatient offices, and nursing homes in O lmsted C ounty, M innesota. Participants Over the 15‐year study period (1988–2002), 1,116 elderly adults underwent surgical repair of a hip fracture. Measurements At the end of the first 7 days after hip fracture repair, participants were classified into one of three groups: clinically verified MI (cv‐ MI ), subclinical myocardial ischemia, and no myocardial ischemia. One‐year mortality was compared between these groups. Multivariate models assessed risk factors for early postoperative cv‐ MI and 1‐year mortality. Results Within the first 7 days after hip fracture repair, 116 (10.4%) participants experienced cv‐ MI and 41 (3.7%) subclinical myocardial ischemia. Overall 1‐year mortality was 22%, with no difference between those with subclinical myocardial ischemia and those with no myocardial ischemia. One‐year mortality for those with cv‐ MI (35.8%) was significantly higher than for the other two groups. Occurrence of early postoperative cv‐ MI , male sex, and history of heart failure or dementia were independently associated with greater 1‐year mortality, whereas prefracture home residence and preoperative higher hemoglobin were protective. Conclusion Rates of early postoperative, cv‐ MI after hip fracture repair exceed rates after other major orthopedic surgeries and are independently associated with greater 1‐year mortality.

Mini‐AbstractWe present a case of a 76‐year‐old woman with new‐onset atrial flutter who underwent transesophageal echocardiography, which demonstrated a large left atrial mass consistent with myxoma and a “shimmering” mobile mass on the aortic side of the right coronary cusp, with fronds consistent with a papillary fibroelastoma. Such concurrent primary cardiac tumors of different histology are a rare occurence.