Effect of Statin Intensity on the Progression of Cardiac Allograft Vasculopathy

Background: In the non-transplant population, hyperlipidaemia has shifted from targeting LDL goals to statin intensity-based treatment. It is unknown whether this strategy is also beneficial in cardiac transplantation. Methods: This single-centre retrospective study evaluated the effect of statin use and intensity on time to cardiac allograft vasculopathy (CAV) after cardiac transplantation. Kaplan–Meier and Cox proportional hazards regression survival methods were used to assess the association of statin intensity and median post-transplant LDL on CAV-free survival. Results: The study involved 143 adults (71% men, average follow-up of 25 ± 14 months) who underwent transplant between 2013 and 2017. Mean CAV-free survival was 47.5 months (95% CI [43.1–51.8]), with 29 patients having CAV grade 1 or greater. Median LDL was not associated with time to CAV (p=0.790). CAV-free survival did not differ between intensity groups (p=0.435). Conclusion: Given the non-statistically significant difference in time to CAV with higher intensity statins, the data suggest that advancing moderate- or high-intensity statin after cardiac transplantation may not provide additional long-term clinical benefit. Trial registration: Not applicable

Development of the interRAI Pressure Ulcer Risk Scale (PURS) for use in long-term care and home care settings

<p>Abstract</p> <p>Background</p> <p>In long-term care (LTC) homes in the province of Ontario, implementation of the Minimum Data Set (MDS) assessment and The Braden Scale for predicting pressure ulcer risk were occurring simultaneously. The purpose of this study was, using available data sources, to develop a bedside MDS-based scale to identify individuals under care at various levels of risk for developing pressure ulcers in order to facilitate targeting risk factors for prevention.</p> <p>Methods</p> <p>Data for developing the interRAI Pressure Ulcer Risk Scale (interRAI PURS) were available from 2 Ontario sources: three LTC homes with 257 residents assessed during the same time frame with the MDS and Braden Scale for Predicting Pressure Sore Risk, and eighty-nine Ontario LTC homes with 12,896 residents with baseline/reassessment MDS data (median time 91 days), between 2005-2007. All assessments were done by trained clinical staff, and baseline assessments were restricted to those with no recorded pressure ulcer. MDS baseline/reassessment samples used in further testing included 13,062 patients of Ontario Complex Continuing Care Hospitals (CCC) and 73,183 Ontario long-stay home care (HC) clients.</p> <p>Results</p> <p>A data-informed Braden Scale cross-walk scale using MDS items was devised from the 3-facility dataset, and tested in the larger longitudinal LTC homes data for its association with a future new pressure ulcer, giving a c-statistic of 0.676. Informed by this, LTC homes data along with evidence from the clinical literature was used to create an alternate-form 7-item additive scale, the interRAI PURS, with good distributional characteristics and c-statistic of 0.708. Testing of the scale in CCC and HC longitudinal data showed strong association with development of a new pressure ulcer.</p> <p>Conclusions</p> <p>interRAI PURS differentiates risk of developing pressure ulcers among facility-based residents and home care recipients. As an output from an MDS assessment, it eliminates duplicated effort required for separate pressure ulcer risk scoring. Moreover, it can be done manually at the bedside during critical early days in an admission when the full MDS has yet to be completed. It can be calculated with established MDS instruments as well as with the newer interRAI suite instruments designed to follow persons across various care settings (interRAI Long-Term Care Facilities, interRAI Home Care, interRAI Palliative Care).</p

Patterns, predictors and subsequent outcomes of disease progression in metastatic renal cell carcinoma patients treated with nivolumab

Abstract Background Nivolumab is approved for the treatment of refractory metastatic renal cell carcinoma. Patterns and predictors of progressive disease (PD) on nivolumab, and outcomes in such patients are lacking. Methods A retrospective analysis of patients (pts) with metastatic clear cell renal cell carcinoma (ccRCC) who received nivolumab at Cleveland Clinic (2015–2017) was performed. PD was defined per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or clinical progression as per treating physician. Univariate analyses (UVA) and multivariate analyses (MVA) were used to identify clinical and laboratory markers as potential predictors of progression-free survival (PFS). Results Ninety patients with mean age of 65, 74% men, and 83% good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. Median number of prior systemic treatments was 2 (range, 1–6). Median overall survival (OS) and PFS were 15.8 and 4.4 months, respectively. Fifty-seven patients (63%) had PD and 44% of patients with radiographic PD had new organ sites of metastases with brain (8/23, 35%) being the most common. Twelve patients received treatment beyond progression (TBP), and among 6 patients with available data, 3 (50%) had any tumor shrinkage (2 pts. with 17% shrinkage, one pt. with 29% shrinkage). Of 57 patients with PD, 28 patients (49%) were able to initiate subsequent treatment, mainly with axitinib and cabozantinib, while 40% of patients were transitioned to hospice after PD. In MVA, a higher baseline Neutrophil-to-Lymphocyte ratio (NLR) (HR, 1.86; 95% CI, 1.05–3.29; p = 0.033) was associated with an increased risk of progression, whereas higher (> 0.1 k/uL) baseline eosinophil count was associated with a lower risk of progression (HR, 0.54; 95% CI, 0.30–0.98; p = 0.042). Conclusion Brain was the most common site of PD in patients treated with nivolumab, and only half of patients progressing on nivolumab were able to initiate subsequent treatment. The risk of PD increased with a higher baseline NLR and reduced with a higher baseline eosinophil count

Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors.

PurposeImmune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti-PD-1 pathway-targeted therapy.Patients and methodsPatients with metastatic RCC who received prior anti-PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed.ResultsForty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients.ConclusionIpilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition

Multiple Origins of Neocortex: Contributions of the Dorsal Ventricular Ridge

The uniqueness of mammalian neocortex may ultimately only be clarified with improved understanding of the evolutionary origins of cortical structure and cortical functions. Comparative studies of the organization of the nonmammalian and mammalian telencephalon may provide valuable clues for understanding the evolution of neocortex. In the nonmammalian telencephalon, there are neuronal populations which correspond to cell groups in the neocortex of mammals in terms of connections, single unit-responses, and functions. Some of these populations lying within the dorsal ventricular ridge, however, are organized in a non-laminar, rather than laminar fashion. These observations suggest that the emergence of basic “cortical” circuit and laminar organization are distinct evolutionary events that can be differentiated and studied independently in order to understand each of their respective contributions to the cognitive functions of the neocortex. Moreover, in contrast to an argument that many cortical visual areas are derived from a single area by gene duplication (Allman, 1977, in press), the origins of neocortex can be separable into at least the precursors of non-laminar and laminar regions, and thus multiple evolutionary origins of neocortex are proposed