Citations

Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory‐related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to characterize respiratory‐related adverse events (AEs) associated with current or recent treatment with inhaled treprostinil and to compare the incidence of respiratory‐related AEs in PAH patients treated with inhaled treprostinil with that in patients treated with other Food and Drug Administration (FDA)–approved PAH therapies. This was a long‐term, prospective, observational study. All respiratory‐related AEs were recorded during the study. The number of PAH patients enrolled was 1,333, 666 treated with inhaled treprostinil and 667 controls (treated with an FDA‐approved PAH therapy other than inhaled treprostinil), for a total of 958 and 1,094 patient‐years of exposure, respectively. In the inhaled‐treprostinil group, 1,281 respiratory‐related AEs were reported in 403 patients (61%), and in the control group, 1,295 respiratory‐related AEs were reported in 388 patients (58%). Cough, throat irritation, nasal discomfort, and hemoptysis were the most common respiratory‐related AEs (occurring in ≥2% of patients in either treatment group) that demonstrated a higher number of events per patient‐year of exposure in the inhaled‐treprostinil group than in the control group (risk ratio [95% confidence interval]: 1.487 [1.172–1.887], 3.777 [2.050–6.956], 2.039 [1.072–3.879], and 1.957 [1.024–3.741], respectively). Overall, inhaled treprostinil was well tolerated by PAH patients in routine clinical care, with respiratory‐related AEs consistent with the known safety profile (trial registration: clinicaltrials.gov identifier: NCT01266265).

BACKGROUND. Variable response to chemotherapy in acute myeloid leukemia (AML) represents a major treatment challenge. Clinical and genetic features incompletely predict outcome. The value of clinical epigenetic assays for risk classification has not been extensively explored. We assess the prognostic implications of a clinical assay for multilocus DNA methylation on adult patients with de novo AML. METHODS. We performed multilocus DNA methylation assessment using xMELP on samples and calculated a methylation statistic (M-score) for 166 patients from UPENN with de novo AML who received induction chemotherapy. The association of M-score with complete remission (CR) and overall survival (OS) was evaluated. The optimal M-score cut-point for identifying groups with differing survival was used to define a binary M-score classifier. This classifier was validated in an independent cohort of 383 patients from the Eastern Cooperative Oncology Group Trial 1900 (E1900; NCT00049517). RESULTS. A higher mean M-score was associated with death and failure to achieve CR. Multivariable analysis confirmed that a higher M-score was associated with death ( P = 0.011) and failure to achieve CR ( P = 0.034). Median survival was 26.6 months versus 10.6 months for low and high M-score groups. The ability of the M-score to perform as a classifier was confirmed in patients ≤ 60 years with intermediate cytogenetics and patients who achieved CR, as well as in the E1900 validation cohort. CONCLUSION. The M-score represents a valid binary prognostic classifier for patients with de novo AML. The xMELP assay and associated M-score can be used for prognosis and should be further investigated for clinical decision making in AML patients.

ABSTRACT We describe a 16-year-old neutropenic patient from the Middle East with bloodstream infection caused by two carbapenemase-producing Escherichia coli isolates that we characterized by whole-genome sequencing. While one displayed meropenem resistance and was bla NDM positive, the other demonstrated meropenem susceptibility yet harbored bla OXA181 (which encodes a bla OXA48 -like enzyme). This report highlights the challenge of laboratory detection of bla OXA48 -like enzymes and the clinical implications of genotypic resistance detection in carbapenemase-producing Enterobacteriaceae .

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD42013003526.

Purpose To develop a system prognostic of outcome in those undergoing allogeneic hematopoietic cell transplantation (allo HCT) for myelodysplastic syndrome (MDS). Patients and Methods We examined 2,133 patients with MDS undergoing HLA-matched (n = 1,728) or -mismatched (n = 405) allo HCT from 2000 to 2012. We used a Cox multivariable model to identify factors prognostic of mortality in a training subset (n = 1,151) of the HLA-matched cohort. A weighted score using these factors was assigned to the remaining patients undergoing HLA-matched allo HCT (validation cohort; n = 577) as well as to patients undergoing HLA-mismatched allo HCT. Results Blood blasts greater than 3% (hazard ratio [HR], 1.41; 95% CI, 1.08 to 1.85), platelets 50 × 109/L or less at transplantation (HR, 1.37; 95% CI, 1.18 to 1.61), Karnofsky performance status less than 90% (HR, 1.25; 95% CI, 1.06 to 1.28), comprehensive cytogenetic risk score of poor or very poor (HR, 1.43; 95% CI, 1.14 to 1.80), and age 30 to 49 years (HR, 1.60; 95% CI, 1.09 to 2.35) were associated with increased hazard of death and assigned 1 point in the scoring system. Monosomal karyotype (HR, 2.01; 95% CI, 1.65 to 2.45) and age 50 years or older (HR, 1.93; 95% CI, 1.36 to 2.83) were assigned 2 points. The 3-year overall survival after transplantation in patients with low (0 to 1 points), intermediate (2 to 3), high (4 to 5) and very high (≥ 6) scores was 71% (95% CI, 58% to 85%), 49% (95% CI, 42% to 56%), 41% (95% CI, 31% to 51%), and 25% (95% CI, 4% to 46%), respectively (P < .001). Increasing score was predictive of increased relapse (P < .001) and treatment-related mortality (P < .001) in the HLA-matched set and relapse (P < .001) in the HLA-mismatched cohort. Conclusion The proposed system is prognostic of outcome in patients undergoing HLA-matched and -mismatched allo HCT for MDS.

ABSTRACT Introduction Penile prosthesis implantation has emerged as a definitive treatment to restore sexual function to the motivated man with erectile dysfunction. Substantial improvements in the design of inflatable devices have been made since they first became available more than four decades ago. Aim To review the history of the penile prosthesis, the indications, preoperative evaluation, and patient and partner satisfaction. The current approaches to addressing intra- and postoperative complications, provide an understanding of prosthesis infection, and placement of these devices will be reviewed. Methods A committee of worldwide experts in this field was assembled during the 2015 International Consultation on Sexual Medicine (ICSM) and performed a systematic review of the peer-reviewed published medical literature pertaining to penile prosthesis. Particular attention was given to higher level trials when available. Recommendations are based upon the Oxford Criteria. Main Outcome Measures Unfortunately there is limited level 1 and 2 evidence, and where expert opinion was utilized, the decision was unanimous within the committee with a goal of presenting a clinically relevant guideline pertaining to penile prostheses. Results Penile prosthesis has undergone an evolution over the past 40 years resulting in a more effective and reliable treatment for advanced erectile dysfunction not responding to less invasive methods including oral treatment with PDE5 inhibitors, vacuum erection device, and intracorporal injection therapy. It should be considered an appropriate treatment option for the man who wishes to restore erectile function and who understands the potential risk of mechanical failure and infection, both of which are less common now as a result of improvements made in device design as well as surgical protocols adhered to in the operating room. Patients must be clearly informed of the risks associated with penile prosthesis including mechanical failure, infection, shortening of the penis, change in sensation and configuration of the penis, as well as injury to local structures. Intraoperative complications are unusual but do occur and can usually be addressed intraoperatively to allow placement of the device at the time of initial surgery. Postoperative complications may also be addressed when they occur but may require more advanced reconstructive surgical techniques. Men with Peyronie's disease, corporal fibrosis due to infection, trauma, prior prosthesis explantation, priapism, and men who have undergone construction of a neophallus may require additional advanced maneuvers to obtain optimum results with a penile prosthesis. Conclusion Penile prosthesis remains as an important, viable, and effective treatment for male erectile dysfunction that does not respond to other less invasive approaches or when these approaches are contraindicated or not acceptable to the patient. These devices provide the patient with the ability to engage in penetrative sexual activity without interfering with urination, ejaculation, sensation, or orgasm. Although mechanical failure can occur, the current devices are more reliable as a result of design modifications. Infection remains the most dreaded complication but since the introduction of antibiotic and hydrophilic coatings, infection is less common. Overall, patient and partner satisfaction appear to be reasonably high when a penile prosthesis is used to restore erectile function.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease characterized by infiltration of the lung, pleura and mediastinum with thin-walled lymphangiomas. DPL can result in mass effect from infiltrative disease, restrictive and obstructive pulmonary physiology, chylous effusions and respiratory failure. The present article discusses clinical, radiographic and pathological features, and treatment options for DPL.