No abstract

Although African Americans have lower intrahepatic triglyceride accumulation, once NAFLD develops, NASH occurs as frequently, and as severe, as in Caucasian patients. Therefore, African Americans with NAFLD should be screened for NASH with the same degree of clinical resolve as in Caucasian patients.

No abstract

The first author's name was incorrectly spelled in the initial online publication.The original article has been corrected.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Early initiation of maintenance hemodialysis has been associated with excess mortality in some studies, but the effects on cardiovascular (CV) mortality has not been studied. Moreover, whether the increased mortality is due to co-morbidities or early initiation of dialysis is unclear. We used a propensity score weighted analysis of the United States Renal Data System (USRDS) to examine how the estimated glomerular filtration rate (eGFR) at initiation of dialysis affects total and CV mortality. Methods: Association between tertiles of eGFR at initiation of hemodialysis and all-cause and CV mortality were assessed in 676,196 adult patients who initiated hemodialysis between 2006 and 2014, using inverse probability of treatment weighting (IPTW) weighted multivariable regression models. Results: The intermediate (eGFR 8.7 to <13.0 mL/min) and early start groups (eGFR ≥13.0 mL/ min) had a 42% and 93% increased all-cause mortality, respectively compared to late (eGFR < 8.7), start group (unadjusted hazard ratio (HR) = 1.42; 95% CI, 1.41-1.43 and HR = 1.93; 95%CI, 1.91-1.94, respectively). This association was attenuated but remained significant in propensity weighted multivariable analysis (adjusted HR = 1.13; 95%CI, 1.12-1.14 for intermediate and HR = 1.37; 95%CI, 1.36-1.39, for early start, respectively). The CV mortality was similarly increased (adjusted HR = 1.08; 95%CI, 1.07-1.10 and HR = 1.23; 95%CI, 1.21-1.24, for intermediate and early start, respectively). In patients with cystic kidney disease, all-cause mortality was increased with early start, but there were no differences in CV mortality between groups. Conclusions: Early initiation of dialysis is associated with increased all-cause and CV mortality. Our observations support delaying hemodialysis according to the eGFR values.

Patients with chronic kidney disease (CKD) are at increased risk for adverse cardiovascular events. CKD is associated with increases in arterial stiffness while improvements of arterial stiffness, correlates with better survival. However, arterial stiffness is increased early in CKD suggesting there might be additional factors, unique to kidney disease, that increase arterial stiffness. Lysyl Oxidase (LOX) is a key mediator of collagen cross-linking and matrix remodeling. LOX is predominantly expressed in the cardiovascular system and its up regulation has been associated with increased tissue stiffening and extracellular matrix remodeling. Thus, the present study was designed to evaluate the role of increased LOX activity in inducing aortic stiffness in CKD and if β-aminopropionitrile (BAPN), a LOX inhibitor could prevent aortic stiffness by reducing collagen cross-linking. Eight-week-old male C57BL/6 mice were subjected to 5/6 nephrectomy (Nx) or Sham surgery. After surgery, mice were randomized to BAPN (300 mg/kg/day) or vehicle treatment for 4-weeks. Aortic stiffness was assessed by pulse wave velocity (PWV) using Doppler ultrasound. Aortic levels of LOX were assessed by ELISA and cross-linked, total collagen levels were analyzed by Mass spectrometry and Sircol assay respectively. Nx mice showed increased PWV, aortic wall remodeling compared to control mice. Collagen cross-linking was increased in parallel with the increases in total collagen in the aorta of Nx mice. In contrast, Nx mice that received BAPN treatment showed decreased cross-linked collagens and PWV compared to vehicle treatment. Our results indicated that LOX might be an early and key mediator of aortic stiffness in CKD.

Radiation recall dermatitis (RRD) is a rare complication that occurs after completion of radiation therapy (RT) and initiation of a precipitating agent, most commonly chemotherapeutic medications. Various theories attempt to explain the mechanism, including activation of the body's inflammatory pathways through nonimmune activation. Likewise, radiation-induced organizing pneumonia (RIOP) is an infrequent but potentially life-threatening complication of RT that, while not fully understood, is suspected to be partly an autoimmune reaction. Patient: We present the case of a 71-year-old female with a history of type 2 diabetes mellitus, hypothyroidism, interstitial cystitis, and osteoarthritis who presented with clinical stage T1N0M0 ER+/PR-/HER2-invasive ductal carcinoma of the lower outer quadrant of the left breast, for which she underwent left segmental mastectomy and sentinel lymph node biopsy followed by completion axillary lymph node dissection. Her final pathologic stage was T1N1M0. Result: The patient developed RRD and later RIOP following receipt of radiation and chemotherapy, which resolved with steroid administration. Conclusions: The rarity of both RRD and RIOP occurring in a patient, as in our case, suggests a shared pathophysiology behind these two complications. As both reactions involve some degree of inflammation and respond to corticosteroids, it seems likely that the etiologies of RRD and RIOP lie within the inflammatory pathway. However, further investigation should evaluate the frequency, duration, and triggering of concomitant RRD and RIOP.

BACKGROUND Report disease control, survival outcomes, and acute radiotherapy related toxicity among young adult medulloblastoma patients who received proton craniospinal irradiation (CSI) as part of multimodality therapy. We reports the completion rates of planned adjuvant chemotherapy. METHODS All adult medulloblastoma patients (≥ 22 years old) who received postoperative proton CSI +/- chemotherapy at our institution between 2008 and 2020 were included. Patient, disease, and treatment details along with prospectively obtained patient-reported acute CSI toxicities were collected (CTCAE v3 or v4). Acute hematologic data were analyzed. RESULTS Twenty young adult medulloblastoma patients were included. The median age at diagnosis was 27 years (range, 22–30). 45% had high-risk disease. 75% received chemotherapy, most of whom (65%) received post-CSI chemotherapy. Eight patients (40%) received concurrent vincristine with CSI. The median CSI dose was 36 GyE (range, 23.4-36) with a median tumor bed boost of 54 GyE (54-55.8). The median duration of radiotherapy was 44 days (range, 40-49). There were no acute ≥ grade 3 gastrointestinal or hematologic toxicities attributable to CSI (during or within 4 weeks after completion of RT). Grade 2 nausea and vomiting affected 25% and 5% of patients, respectively. Acute grade 2 hematologic toxicity affected 36% of patients. Among patients planned to receive adjuvant chemotherapy (n=13), 100% completed at least 4 cycles and 85% completed all planned chemo cycles. With a median follow-up of 3.1 years, 4-year actuarial local control, DFS, and OS were 90% (95% CI 53-99), 90% (95% CI 53-99), and 95% (95% CI 72-99), respectively. Two patients had disease recurrence, both with local failures in the high dose boost volume in the tumor bed. CONCLUSIONS Proton radiotherapy for CSI in young adult medulloblastoma patients is well tolerated and shows promising disease control and survival outcomes. These data support the standard use of proton CSI for adult medulloblastoma.