Citations

Introduction. The diagnostic standard forPneumocystis jiroveciipneumonia (PCP) is direct microscopic identification; however, in recent years, polymerase chain reaction (PCR) from bronchoalveolar lavage (BAL) samples to detectPneumocystisnucleic acids has proven to be more sensitive and specific. Sputum samples have been presumed inferior to bronchoscopic samples secondary to variability and adequacy of sample collection. We observed several cases of positive sputum PCP-PCR results with negative PCP-PCR BAL results. The aim of the current study was to further characterize the clinical setting and outcomes in patients with positive sputum PCP-PCR samples and negative BAL PCP-PCR samples.Methods. We identified all patients who underwentP. jirovecii-PCR testing at Mayo Clinic between 2011 and 2016. Patients with a positive sputum and negative BAL sample collected within a 14-day time frame were identified and underwent further chart review for demographics, immunocompromised state, and clinical outcome.Results. From 2011 to 2016, 4431 respiratory samples from 3021 unique patients were tested for the presence ofP. jiroveciiby PCR. Fifty-five samples (1.2% of all samples collected) belonging to 24 unique patients (0.79% of patients tested) were identified as having a positive and negative sample collected within 14 days. Of these 24 patients, 10 (46%) patients had a positive sputum or tracheal secretion sample with negative BAL or bronchial washings. Out of these 10 patients, 8 were immunocompromised and 9 underwent treatment for PCP with 6 patients improving.Conclusion. Our results suggest that discordantP. jirovecii-PCR testing results from sputum and bronchoscopic specimens are an infrequent occurrence. Patients with positiveP. jirovecii-PCR sputum/tracheal secretion samples and negative bronchoscopic samples appear to be clinically infected and respond to PCP treatment. SputumP. jirovecii-PCR testing may be a viable alternative to invasive testing.

Key Points λ Light chain AL amyloidosis is associated with a shorter PFS and OS compared with κ. Light chain type predicts likelihood of organ involvement in AL amyloidosis.

Purpose Autologous stem-cell transplantation (ASCT) has been used in patients with immunoglobulin light chain (AL) amyloidosis for more than two decades. Early experience raised concerns regarding safety with high early-mortality rates. Patients and Methods We report 20 years of experience with ASCT for AL amyloidosis at the Mayo Clinic Rochester. In all, 672 consecutive patients receiving ASCT for AL amyloidosis were divided into three cohorts on the basis of date of transplantation (cohort 1, 1996-2002 [n = 124]; cohort 2, 2003-2009 [n = 302]; and cohort 3, 2010-2016 [n = 246]). Results The median age for the entire cohort was 59 years, with patients in cohort 3 being slightly older than those in the other two cohorts (60 v 58 v 54 years for cohorts 3, 2, and 1, respectively; P < .001). Fewer patients in cohort 3 had more than two organs involved (9% v 18% v 19% for cohorts 3, 2, and 1, respectively; P < .001). More patients received pretransplantation therapy in cohort 3 compared with earlier time periods (49% v 38% v 42% for cohorts 3, 2, and 1, respectively; P = .02). Hematologic response was higher in cohort 3 (84% v 79% v 69% for cohorts 3, 2, and 1, respectively; P = .002). Median overall survival for the entire cohort was 122 months and improved over time (not reached v 120 months v 75 months for cohorts 3, 2, and 1, respectively; P < .001). Treatment-related mortality declined over time (2.4% v 8.6% v 14.5% for cohorts 3, 2, and 1, respectively; P < .001). On multivariable analysis, conditioning dose, Mayo stage 2012, and hematologic response were independent predictors of survival. Conclusion ASCT is a highly effective therapy for AL amyloidosis. The improved survival and markedly reduced treatment-related mortality in eligible patients indicate that this will remain an important first-line option even in the era of treatment approaches that use novel agents.

Abstract Purpose: Folate receptor alpha (FR) is overexpressed in several cancers. Endogenous immunity to the FR has been demonstrated in patients and suggests the feasibility of targeting FR with vaccine or other immune therapies. CD4 helper T cells are central to the development of coordinated immunity, and prior work shows their importance in protecting against relapse. Our previous identification of degenerate HLA-class II epitopes from human FR led to the development of a broad coverage epitope pool potentially useful in augmenting antigen-specific immune responses in most patients. Patients and Methods: We conducted a phase I clinical trial testing safety and immunogenicity of this vaccine, enrolling patients with ovarian cancer or breast cancer who completed conventional treatment and who showed no evidence of disease. Patients were initially treated with low-dose cyclophosphamide and then vaccinated 6 times, monthly. Immunity and safety were examined during the vaccine period and up to 1 year later. Results: Vaccination was well tolerated in all patients. Vaccine elicited or augmented immunity in more than 90% of patients examined. Unlike recall immunity to tetanus toxoid (TT), FR T-cell responses developed slowly over the course of vaccination with a median time to maximal immunity in 5 months. Despite slow development of immunity, responsiveness appeared to persist for at least 12 months. Conclusions: The results demonstrate that it is safe to augment immunity to the FR tumor antigen, and the developed vaccine is testable for therapeutic activity in most patients whose tumors express FR, regardless of HLA genotype. Clin Cancer Res; 24(13); 3014–25. ©2018 AACR.

OBJECTIVEAneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities.METHODSThree silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated.RESULTSThe mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4–1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001).CONCLUSIONSThe detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4–2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.

Abstract Background After radical prostatectomy (RP), erectile dysfunction, often necessitating the need for inflatable penile prosthesis (IPP) insertion, and urinary incontinence and climacturia can ensue. Aim To assess the efficacy and safety of the mini-jupette, a mesh used to approximate the medial aspects of the 2 corporotomies at the time of IPP insertion, for the management of climacturia and urine leakage in patients with minimal incontinence. Methods We conducted a pilot multicenter study of patients with post-RP erectile dysfunction and climacturia and/or mild urinary incontinence (≤2 pads/day [ppd]) undergoing IPP insertion with concomitant placement of a mini-jupette graft. Outcomes Pre- and postoperative erectile function, continence and climacturia, and overall surgical outcomes were assessed. Results 38 patients underwent the mini-jupette procedure. The mean age of the population was 65.3 years (SD = 7.7). 30 had post-RP climacturia and 32 patients had post-RP incontinence (mean = 1.3 ppd, SD = 0.8). 31 patients received Coloplast Titan, 4 received AMS 700 LGX, and 3 received AMS 700 CX IPPs. Mean corporotomy size was 2.9 cm (SD = 1.0). Mean graft measurements were 3.2 cm (SD = 0.9) for width, 3.3 cm (SD = 1.3) for length, and 11.0 cm2 (SD = 5.1) for surface area. At a mean follow-up of 5.1 months (SD = 6.9), there were 5 postoperative complications (13.2%) of which 4 required explantation. Climacturia and incontinence were subjectively improved in 92.8% and 85.7%, respectively. Mean ppd decreased by 1.3 postoperatively. Clinical Implications The Andrianne mini-jupette is a feasible adjunct to IPP placement that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. Strengths and Limitations Strengths of this study include the novel nature of this intervention, the multi-institutional nature of the study, and the promising results demonstrated. Limitations include the retrospective nature of the study and the heterogeneity of the techniques and grafts used by different surgeons involved. Conclusion Longer follow-up and larger patient cohorts are needed to confirm the long-term safety and benefits of this intervention.

Objectives: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. Data Sources: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. Study Selection: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. Data Extraction: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. Data Synthesis: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49–64%) at hospital discharge and 32% (95% CI, 21–45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements. Conclusions: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered.