Citations

Abstract Background Fluoroquinolones (FQ) are among the most commonly prescribed antibiotics. Nephrotoxicity related to FQ use is infrequently reported and the mechanism of renal injury is incompletely elucidated. We describe clinical manifestations and outcome of patients with biopsy proven acute interstitial nephritis (AIN) associated with FQ use at our institution. Methods We conducted a retrospective review of biopsy-proven AIN attributed to FQ use at Mayo Clinic Rochester from 1993 to 2016. Cases were reviewed by a renal pathologist and attributed to FQ use by an expert nephrologist. We also reviewed and summarized all published case reports of biopsy proven AIN that were attributed to FQ use. Results We identified 24 patients with FQ-related biopsy-proven AIN. The most commonly used FQ was ciprofloxacin (71%) with median antibiotic treatment duration of 7 days (Figure 1). The median duration between starting FQ and the diagnosis of AIN was 8.5 (IQR: 17). Common clinical manifestations included fever (50%), flank pain (8%), and skin rash (21%). However, 17% of the patients were asymptomatic at the time of diagnosis (Figure 2). Majority (58%) of the patients recovered following discontinuation of antibiotics and returned to baseline renal function at a median of 20.5 (IQR: 15.5). Six patients required temporary hemodialysis and 9 patients received steroids. Conclusion Onset of FQ-related AIN can be delayed and a high index of suspicion is needed by physicians prescribing these agents. Overall outcomes are favorable with recovery to baseline renal function within 3 weeks of discontinuing the offending drug. Disclosures All authors: No reported disclosures.

Schwannomas are benign soft-tissue tumors that arise from peripheral nerve sheaths throughout the body and are commonly encountered in patients with neurofibromatosis Type 2. The vast majority of schwannomas are benign, with rare cases of malignant transformation reported. In this pictorial review, we discuss the magnetic resonance imaging (MRI) appearance of schwannomas by demonstrating a collection of tumors from different parts of the body that exhibit similar MRI characteristics. We review strategies to distinguish schwannomas from malignant soft-tissue tumors while exploring the anatomic and histologic origins of these tumors to discuss how this correlates with their imaging findings. Familiarity with the MRI appearance of schwannomas can help aid in the differential diagnosis of soft-tissue masses, especially in unexpected locations.

AbstractAchievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Objective: New, value-based regulations and reimbursement structures are creating historic care management challenges, thinning the margins and threatening the viability of hospitals and health systems. The Society of Critical Care Medicine convened a taskforce of Academic Leaders in Critical Care Medicine on February 22, 2016, during the 45th Critical Care Congress to develop a toolkit drawing on the experience of successful leaders of critical care organizations in North America for advancing critical care organizations (Appendix 1). The goal of this article was to provide a roadmap and call attention to key factors that adult critical care medicine leadership in both academic and nonacademic setting should consider when planning for value-based care. Design: Relevant medical literature was accessed through a literature search. Material published by federal health agencies and other specialty organizations was also reviewed. Collaboratively and iteratively, taskforce members corresponded by electronic mail and held monthly conference calls to finalize this report. Setting: The business and value/performance critical care organization building section comprised of leaders of critical care organizations with expertise in critical care administration, healthcare management, and clinical practice. Measurements and Main Results: Two phases of critical care organizations care integration are described: “horizontal,” within the system and regionalization of care as an initial phase, and “vertical,” with a post-ICU and postacute care continuum as a succeeding phase. The tools required for the clinical and financial transformation are provided, including the essential prerequisites of forming a critical care organization; the manner in which a critical care organization can help manage transformational domains is considered. Lastly, how to achieve organizational health system support for critical care organization implementation is discussed. Conclusions: A critical care organization that incorporates functional clinical horizontal and vertical integration for ICU patients and survivors, aligns strategy and operations with those of the parent health system, and encompasses knowledge on finance and risk will be better positioned to succeed in the value-based world.

Key Points Organ progression at second-line therapy predicated inferior survival. Patients relapsing from >VGPR had a longer time to develop organ progression.

AbstractOutside of clinical trials, experience with daratumumab‐based combination therapies (DCTs) using bortezomib (V)/lenalidomide (R)/pomalidomide (P), and dexamethasone (d) in relapsed/refractory multiple myeloma (RRMM) is limited. We reviewed the outcomes of 126 patients who received ≥ 1 cycle of any DCT. Median age at DCT initiation was 67 (range, 43‐93) years. High‐risk cytogenetics was present in 33% patients. Median number of prior therapies was 4 (range, 1‐14) and time to first DCT from diagnosis was 4.3 years (range, 0.4‐13.0). Seventeen (13%) patients were refractory to single agent daratumumab. Fifty‐two (41%), 34 (27%), 23 (18%), and 17 (14%) received DPd, DRd, DVd and “other” DCTs, respectively. Overall response rate was 47%. Median follow‐up was 5.5 months (95% CI, 4.2‐6.1). Median progression‐free survival (PFS) was 5.5 months (95% CI, 4.2‐7.8). Median overall survival was not reached (NR) with any regimen. Median PFS (months) was worst for penta‐refractory MM (n = 8) vs quadruple refractory MM (n = 18) and others (n = 100) (2.2 [95% CI, 1‐2.4] vs 3.1 [95% CI, 2.1‐NR] vs 5.9 [95% CI, 5.0‐NR]; P < .001); those who were refractory to ≥1 agents used in the DCT vs others (4.9 [95% CI, 3.1‐6.0] vs 8.2 [95% CI, 4.6‐NR]; P = .02); and those who received >2 prior therapies vs others (5.0 months [95% CI, 3.7‐5.9] vs NR [95% CI, NR‐NR]; P = .002). Non‐hematologic toxicities included infections (38%), fatigue (32%), and infusion reactions (18%). Grade 3 or higher hematological toxicities were seen in 41% of patients. DCTs are effective in RRMM. ORR and PFS in heavily pretreated patients are lower than those reported in clinical trials.

SummaryThe management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression‐free survival (PFS) and time‐to‐next‐therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty‐five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well‐tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed‐duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.

Abstract Introduction Identifying at what point atrophy rates first change in Alzheimer's disease is important for informing design of presymptomatic trials. Methods Serial T1‐weighted magnetic resonance imaging scans of 94 participants (28 noncarriers, 66 carriers) from the Dominantly Inherited Alzheimer Network were used to measure brain, ventricular, and hippocampal atrophy rates. For each structure, nonlinear mixed‐effects models estimated the change‐points when atrophy rates deviate from normal and the rates of change before and after this point. Results Atrophy increased after the change‐point, which occurred 1–1.5 years (assuming a single step change in atrophy rate) or 3–8 years (assuming gradual acceleration of atrophy) before expected symptom onset. At expected symptom onset, estimated atrophy rates were at least 3.6 times than those before the change‐point. Discussion Atrophy rates are pathologically increased up to seven years before “expected onset”. During this period, atrophy rates may be useful for inclusion and tracking of disease progression.