Postoperative acute kidney injury and renal replacement therapy after DCD lung transplantation.

Acute kidney injury (AKI) after lung transplantation (LTx) is a common complication. We aimed to assess whether donation after circulatory death (DCD) is associated with an increased risk of AKI and renal replacement therapy (RRT) in the early postoperative period compared to the donation after brain death (DBD). Retrospective data on a cohort (N = 95) of LTx patients (DCD n = 17, DBD n = 78) characterized by no use of ex-vivo lung perfusion were analyzed for the incidence of AKI within 30 postoperative days and incidence of RRT within 7 and 30 days. After optimal full matching, an imbalance remained between the DCD and DBD patients in respect to intraoperative use of cardiopulmonary bypass (CPB). Therefore, a further subset (n = 77) was defined that excluded CPB patients, and matching was repeated (DCD n = 13 vs. DBD n = 63) resulting in a fair balance on a range of preoperative characteristics and intraoperative use of ECMO. In both matched subsets, DCD was associated with around twice higher risk of AKI and RRT within 7 and 30 postoperative days. In conclusion, data suggest that DCD could be associated with worse early renal outcomes in a subset of LTx patients and justify further studies on the topic in order to refine further renal care pathways perioperatively.

Midterm outcomes of venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation: Comparison with nonbridged recipients.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation (VV-ECMO) is increasingly being used in acutely deteriorating patients with end-stage lung disease as a bridge to transplantation (BTT). It can allow critically ill recipients to remain eligible for lung transplants (LTx) while reducing pretransplant deconditioning. We analyzed early- and midterm postoperative outcomes of patients on VV-ECMO as a BTT and the impact of preoperative VV-ECMO on posttransplant survival outcomes. METHODS: All consecutive LTx performed at our institution between January 2012 and December 2018 were analyzed. After matching, BTT patients were compared with nonbridged LTx recipients. RESULTS: Out of 297 transplanted patients, 21 (7.1%) were placed on VV-ECMO as a BTT. After matching, we observed similar 30-day mortality between BTT and non-BTT patients (4.6% vs. 6.6%, p = .083) despite a higher incidence of early postoperative complications (need for ECMO, delayed chest closure, and acute kidney injury). Furthermore, preoperative VV-ECMO did not appear associated with 30-day or 1-year mortality in both frequentist and Bayesian analysis (odds ratio [OR]: 0.35, 95% confidence interval: 0.03-3.49, p = .369; OR: 0.27, 95% credible interval: 0.01-3.82, p = 84.7%, respectively). In sensitivity analysis, both subgroups were similar in respect to 30-day (7.8% vs. 6.5%, p = .048) and 1-year mortality (12.5% vs. 18%, p = .154). CONCLUSIONS: Patients with acute refractory respiratory failure while waiting for LTx represent a high-risk cohort of patients. VV-ECMO as a BTT is a reasonable strategy in adult patients with acceptable operative mortality and 1-year survival comparable to non-BTT patients.

Fatigue, anxiety, and quality of life in breast cancer patients compared to non-cancer controls: a nationwide longitudinal analysis.

PURPOSE: Fatigue and anxiety are common and significant symptoms reported by cancer patients. Few studies have examined the trajectory of multidimensional fatigue and anxiety, the relationships between them and with quality of life. METHODS: Breast cancer patients (n = 580) from community oncology clinics and age-matched controls (n = 364) completed fatigue and anxiety questionnaires prior to chemotherapy (A1), at chemotherapy completion (A2), and six months post-chemotherapy (A3). Linear mixed models (LMM) compared trajectories of fatigue /anxiety over time in patients and controls and estimated their relationship with quality of life. Models adjusted for age, education, race, BMI, marital status, menopausal status, and sleep symptoms. RESULTS: Patients reported greater fatigue and anxiety compared to controls at all time points (p's < 0.001, 35% clinically meaningful anxiety at baseline). From A1 to A2 patients experienced a significant increase in fatigue (ß = 8.3 95%CI 6.6,10.0) which returned to A1 values at A3 but remained greater than controls' (p < 0.001). General, mental, and physical fatigue subscales increased from A1 to A2 remaining significantly higher than A1 at A3 (p < 0.001). Anxiety improved over time (A1 to A3 ß = - 4.3 95%CI -2.6,-3.3) but remained higher than controls at A3 (p < 0.001). Among patients, fatigue and anxiety significantly predicted one another and quality of life. Menopausal status, higher BMI, mastectomy, and sleep problems also significantly predicted change in fatigue. CONCLUSION: Breast cancer patients experience significant fatigue and anxiety up to six months post-chemotherapy that is associated with worse quality of life. Future interventions should simultaneously address anxiety and fatigue, focusing on mental and physical fatigue subdomains.

Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma.

PURPOSE: The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide treatment choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitor (ICI) therapy in the real world is not well known. METHODS: Using a deidentified nationwide (US-based) melanoma clinicogenomic database, we identified a real-world cohort of patients with metastatic melanoma (N = 497) who received first-line monotherapy anti-PD-1 (n = 240) or dual anti-PD-1 and anti-CTLA-4 ICI (n = 257) and had a tissue-based comprehensive genomic profiling test TMB score. RESULTS: TMB-high (TMB-H; ≥10 mutations per megabase [muts/Mb], n = 352, 71%) was independently predictive of superior real-world progression-free survival and overall survival versus TMB-low (<10 mut/Mb, n = 145, 29%) in both mono ICI (hazard ratio [HR], 0.45 [95% CI, 0.32 to 0.63]; P < .001; HR, 0.61 [95% CI, 0.41 to 0.90]; P = .01, respectively) and dual ICI (HR, 0.67 [95% CI, 0.49 to 0.90]; P = .009; HR, 0.61 [95% CI, 0.42 to 0.88]; P = .007, respectively) patients. Dual ICI offered no significant advantage in BRAFwt patients and unexpectedly demonstrated greatest benefit in the TMB 10-19 mut/Mb group, identifying a TMB-very high (≥20 mut/Mb, n = 247, 50%) BRAFmut patient subgroup for whom mono ICI may be preferable. CONCLUSION: TMB-H predicts superior outcomes on ICI while coassessment of BRAF status and TMB may inform first-line regimen choice.

Evaluating post-Katrina recovery in Mississippi using repeat photography.

Hurricane Katrina of August 2005 had extensive consequences for the state of Mississippi in the United States. Widespread infrastructure and property damage, massive social dislocation, and ecological loss remain among the many challenges faced by communities as they work towards 'normalcy'. This study employs repeat photography to understand differential recovery from Hurricane Katrina in Mississippi. Revealing change with conventional landscape photography, a process known as repeat photography, is common in the natural sciences. Simply stated, repeat photography is the practice of re-photographing the same scene as it appears in an earlier photograph. Photographs were taken at 131 sites every six months over a three-year period. Each photograph was assigned a recovery score and a spatially interpolated recovery surface was generated for each time period. The mapped and graphed results show disparities in the progression of recovery: some communities quickly entered the rebuilding process whereas others have lagged far behind.

Heart Transplantation in Adult Congenital Heart Disease with the Organ Care System Use: A 4-Year Single-Center Experience.

Recent advances in the management of patients with adult congenital heart disease (ACHD) have led to an increased number of patients who may develop heart failure and require heart transplantation (HTx). The purpose of this study was to evaluate early and mid-term postoperative outcomes after HTx with the use of Organ Care System (OCS) in a cohort of ACHD patients transplanted at our tertiary center. All consecutive HTx performed from January 2015 to January 2019 at our institution were analyzed. Donor and recipient preoperative characteristics, intraoperative course, and perioperative clinical outcomes were evaluated. Nine patients with median age of 44 years (range 17-61 years) underwent isolated HTx for end-stage ACHD during the study period. Mean cold ischemic time was 84 ± 17 minutes. Postoperatively, four patients (44%) needed venoarterial extracorporeal membrane oxygenation (1-7 days). One patient (11%) required surgical re-exploration for bleeding. Thirty-day and 1-year mortality were 11% and 22%, respectively. In our experience, despite the challenges of transplantation in ACHD, these patients can be successfully transplanted with the use of the OCS in a highly specialized center. Careful donor and recipient selection are of paramount importance.

Physical Activity Patterns and Relationships With Cognitive Function in Patients With Breast Cancer Before, During, and After Chemotherapy in a Prospective, Nationwide Study.

PURPOSE: Physical activity (PA) is a promising intervention for cancer-related cognitive decline, yet research assessing its use during chemotherapy is limited. This study evaluated patterns of PA before, during, and after chemotherapy in patients with breast cancer and the association between PA and cognitive function. METHODS: In a nationwide, prospective cohort study, we assessed PA (Aerobics Center Longitudinal Study PA measure) and perceived and objectively measured cognitive functioning (Functional Assessment of Cancer Therapy-Cognitive, Delayed Match to Sample, and Rapid Visual Processing measures) at prechemotherapy (T1), postchemotherapy (T2), and 6 months postchemotherapy (T3) in patients with breast cancer and cancer-free, age-matched controls at equivalent time points. Longitudinal linear mixed-effects models (LMMs) characterized PA changes over time between patients and controls, adjusting for demographic and clinical factors. LMMs further estimated the role of prechemotherapy PA and changes in PA during chemotherapy on cognitive changes over time. RESULTS: Patients with stage I-IIIC breast cancer (n = 580; age M [standard deviation] = 53.4 [10.6] years) and controls (n = 363; age M [standard deviation] = 52.6 [10.3] years) were included. One third of patients met national PA guidelines at T1, dropping to 21% at T2 before rising to 37% at T3. LMMs revealed declines in PA from T1 to T2 in patients compared with controls (all P < .001). Patients meeting guidelines at T1 demonstrated better cognitive scores over time on the Functional Assessment of Cancer Therapy-Cognitive and Rapid Visual Processing (all P < .05), with similar patterns of objectively-measured cognitive function as controls. In patients, greater moderate-to-vigorous PA at the previous time point was significantly associated with better cognitive trajectories (all P < .05), and adherence to PA guidelines throughout chemotherapy was associated with better self-reported cognition (P < .01). CONCLUSION: This nationwide study demonstrates that PA maintenance before and during chemotherapy is associated with better cognitive function immediately and 6 months after chemotherapy completion.

E3611-A Randomized Phase II Study of Ipilimumab at 3 or 10 mg/kg Alone or in Combination with High-Dose Interferon-α2b in Advanced Melanoma.

PURPOSE: Interferon-α favors a Th1 shift in immunity, and combining with ipilimumab (ipi) at 3 or 10 mg/kg may downregulate CTLA4-mediated suppressive effects, leading to more durable antitumor immune responses. A study of tremelimumab and high-dose interferon-α (HDI) showed promising efficacy, supporting this hypothesis. PATIENTS AND METHODS: E3611 followed a 2-by-2 factorial design (A: ipi10+HDI; B: ipi10; C: ipi3+HDI; D: ipi3) to evaluate (i) no HDI versus HDI (across ipilimumab doses) and (ii) ipi3 versus ipi10 (across HDI status). We hypothesized that median progression-free survival (PFS) would improve from 3 to 6 months with HDI versus no HDI and with ipi10 versus ipi3. RESULTS: For eligible and treated patients (N = 81) at a median follow-up time of 29.8 months, median PFS was 4.4 months [95% confidence interval (CI), 2.7-8.2] when ipilimumab was used alone and 7.5 months (95% CI, 5.1-11.0) when HDI was added. Median PFS was 3.8 months (95% CI, 2.6-7.5) with 3 mg/kg ipilimumab and 6.5 months (95% CI, 5.1-13.5) with 10 mg/kg. By study arm, median PFS was 8.0 months (95% CI, 2.8-20.2) in arm A, 6.2 months (95% CI, 2.7-25.7) in B, 5.7 months (95% CI, 1.5-11.1) in C, and 2.8 months (95% CI, 2.6-5.7) in D. The differences in PFS and overall survival (OS) did not reach statistical significance. Adverse events were consistent with the known profiles of ipilimumab and HDI and significantly higher with HDI and ipi10. CONCLUSIONS: Although PFS was increased, the differences resulting from adding interferon-α or a higher dose of ipilimumab did not reach statistical significance and do not outweigh the added toxicity risks.

Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study.

Purpose Cancer-related cognitive impairment is an important problem for patients with breast cancer, yet its trajectory is not fully understood. Some previous cancer-related cognitive impairment research is limited by heterogeneous populations, small samples, lack of prechemotherapy and longitudinal assessments, use of normative data, and lack of generalizability. We addressed these limitations in a large prospective, longitudinal, nationwide study. Patients and Methods Patients with breast cancer from community oncology clinics and age-matched noncancer controls completed the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) at prechemotherapy and postchemotherapy and at a 6-month follow-up as an a priori exploratory aim. Longitudinal models compared FACT-Cog scores between patients and controls at the three assessments and adjusted for age, education, race, menopausal status, and baseline reading ability, anxiety, and depressive symptoms. A minimal clinically important difference cutoff determined percentages of impairment over time. Results Of patients, 581 patients with breast cancer (mean age, 53 years; 48% anthracycline-based regimens) and 364 controls (mean age, 53 years) were assessed. Patients reported significantly greater cognitive difficulties on the FACT-Cog total score and four subscales from prechemotherapy to postchemotherapy compared with controls as well as from prechemotherapy to 6-month follow-up (all P < .001). Increased baseline anxiety, depression, and decreased cognitive reserve were significantly associated with lower FACT-Cog total scores. Treatment regimen, hormone, or radiation therapy was not significantly associated with FACT-Cog total scores in patients from postchemotherapy to 6-month follow-up. Patients were more likely to report a clinically significant decline in self-reported cognitive function than were controls from prechemotherapy to postchemotherapy (45.2% v 10.4%) and from prechemotherapy to 6-month follow-up (36.5% v 13.6%). Conclusion Patients with breast cancer who were treated in community oncology clinics report substantially more cognitive difficulties up to 6 months after treatment with chemotherapy than do age-matched noncancer controls.

Relapsing intracranial plasma cell granuloma: A case report.

Plasma cell granuloma is a pathological entity reported in nearly every organ system; however, intracranial cases remain rare. In the current case report, we present a case of intracranial plasma cell granuloma with the longest known follow-up period in the literature. Medical follow-up over 14 years, detailing four recurrences following the patient's initial presentation and management, is presented. The patient's treatment course consisted of three craniotomies, 3,600-cGy fractionated radiation and two courses of glucocorticoid therapy. In addition to disease surveillance using clinical examination and imaging, this case represents the first description of the clinical utility of analyzing changes in an inflammatory blood marker, the erythrocyte sedimentation rate, which coincided with recurrence and response to therapy.

Aliskiren, an oral renin inhibitor, provides dose-dependent efficacy and sustained 24-hour blood pressure control in patients with hypertension.

OBJECTIVES: This dose-ranging study evaluated the antihypertensive efficacy and tolerability of aliskiren in patients with mild-to-moderate hypertension. BACKGROUND: Low blood pressure (BP) control rates among patients with hypertension indicate a need for improved treatment options. This study investigates aliskiren, the first in a new antihypertensive class called renin inhibitors. METHODS: Patients with mean sitting diastolic BP 95 to 109 mm Hg were randomized to aliskiren 150, 300, or 600 mg or placebo once daily for 8 weeks. Patients completing this treatment phase entered a 2-week treatment-free withdrawal period. Office BP was recorded at baseline, weeks 2, 4, 6, and 8 of treatment, and 4 days and 2 weeks after cessation of treatment. A subgroup of patients underwent ambulatory BP monitoring. RESULTS: In total, 672 patients were randomized to treatment. After 8 weeks, aliskiren 150, 300, and 600 mg significantly reduced mean sitting BP (systolic/diastolic) by 13.0/10.3, 14.7/11.1, and 15.8/12.5 mm Hg, respectively, versus 3.8/4.9 mm Hg with placebo (all p < 0.0001 for systolic and diastolic BP). The BP-lowering effect of aliskiren persisted for up to 2 weeks after treatment withdrawal. Aliskiren significantly reduced mean 24-h ambulatory BP (p < 0.0001 vs. placebo with all doses) exhibiting smooth, sustained effects and high trough-to-peak ratios. Aliskiren was well tolerated; overall adverse event rates were 40.1%, 46.7%, and 52.4% with aliskiren 150, 300, and 600 mg, respectively, and 43.0% with placebo. Few patients discontinued treatment due to adverse events. CONCLUSIONS: Aliskiren provides significant antihypertensive efficacy in patients with hypertension, with no rebound effects on blood pressure after treatment withdrawal.