Citations

An elderly woman was admitted to the Family Medicine inpatient service for altered mental status after being brought to the emergency room by a concerned neighbor, who had come across the patient speaking incoherently. Initial evaluation was notable for elevated blood pressures, but extensive lab testing and head computed tomographic imaging were within normal limits. However, subsequent magnetic resonance imaging showed white matter changes consistent with posterior reversible encephalopathy syndrome (PRES), a neurologic syndrome characterized by headache, altered mental status, loss of vision, and seizures as well as radiographic findings of posterior cerebral white matter edema. Multiple etiologies of PRES have been described and include hypertensive encephalopathy, immunosuppressant medications, and eclampsia. This case describes an episode of PRES secondary to hypertensive encephalopathy brought about by an inappropriate dose of a monoamine oxidase (MAO) inhibitor. The patient had significant improvement in symptoms with removal of the offending agent and control of her blood pressure. While PRES generally has a good prognosis, prompt recognition, and management are important in preventing significant disease morbidity and mortality.

Abstract Heterozygous loss-of-function mutations in the GRN gene lead to progranulin (PGRN) haploinsufficiency and cause frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A). PGRN is a highly conserved, secreted glycoprotein and functions in the central nervous system as a key modulator of microglial function. Hence, altered microglial function caused by PGRN deficiency may be tied to the pathogenesis of FTLD-TDP. Our previous studies showed that haploinsufficiency of GRN mutations extends to microglial PGRN expression in the hippocampal CA1 region. In this study, we found that the CA1 sector was associated with less neuronal loss and more frequent TDP-43 inclusions in FTLD-TDP type A cases with GRN mutations than in sporadic cases. In addition, the CA1 region in GRN mutation cases contained more rod-like microglia, which also had reduced PGRN expression. These findings suggest that the profile of TDP-43 inclusions, neuronal number, and microgliosis in the CA1 sector of FTLD-TDP type A cases may be influenced by GRN gene expression status.

AbstractBackgroundThere are controversial data regarding the relationship between bariatric surgery and atrial fibrillation (AF). This meta‐analysis was performed to evaluate (i) the incidence and (ii) the risk of AF in patients following bariatric surgery.AimsTo explore the incidence and risk factors of AF in patients after bariatric surgery.MethodsA literature search was conducted utilising MEDLINE, EMBASE and Cochrane Database from inception through March 2019. We included studies that evaluated the (i) incidence and (ii) risk of AF in patients after bariatric surgery. Pooled incidence and odds ratios (OR) with 95% confidence interval (CI) were calculated using random effects meta‐analysis.ResultsSeven cohort studies consisting of 7681 patients undergoing bariatric surgery were enrolled in this systematic review. The prevalence of AF in patients undergoing bariatric surgery ranged between 0% and 4.6%. Overall, the pooled estimated incidence of AF following bariatric surgery was 5.3% (95% CI: 1.9–13.8) at a median follow‐up time of 7.9 years (interquartile range (IQR) 4.1–15.0 years). Compared to controls, the pooled OR of AF among patients undergoing bariatric surgery was 0.42 (95% CI: 0.22–0.83) at a median follow‐up time of 7.9 years (IQR 7.2–19.0 years). Egger regression test demonstrated no significant publication bias in our meta‐analysis of AF incidence following bariatric surgery.ConclusionThe overall estimated incidence of AF following bariatric surgery was 5.3%. Our study demonstrates a significant beneficial association between bariatric surgery and AF, with a 0.42‐fold decreased risk of AF. Future large‐scale studies are needed to confirm the potential benefits of bariatric surgery on risk of AF.

Background: Although acute kidney injury (AKI) is a frequent complication in patients receiving extracorporeal membrane oxygenation (ECMO), the incidence and impact of AKI on mortality among patients on ECMO remain unclear. We conducted this systematic review to summarize the incidence and impact of AKI on mortality risk among adult patients on ECMO. Methods: A literature search was performed using EMBASE, Ovid MEDLINE, and Cochrane Databases from inception until March 2019 to identify studies assessing the incidence of AKI (using a standard AKI definition), severe AKI requiring renal replacement therapy (RRT), and the impact of AKI among adult patients on ECMO. Effect estimates from the individual studies were obtained and combined utilizing random-effects, generic inverse variance method of DerSimonian-Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018103527). Results: 41 cohort studies with a total of 10,282 adult patients receiving ECMO were enrolled. Overall, the pooled estimated incidence of AKI and severe AKI requiring RRT were 62.8% (95%CI: 52.1%–72.4%) and 44.9% (95%CI: 40.8%–49.0%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of AKI (p = 0.67) or AKI requiring RRT (p = 0.83). The pooled odds ratio (OR) of hospital mortality among patients receiving ECMO with AKI on RRT was 3.73 (95% CI, 2.87–4.85). When the analysis was limited to studies with confounder-adjusted analysis, increased hospital mortality remained significant among patients receiving ECMO with AKI requiring RRT with pooled OR of 3.32 (95% CI, 2.21–4.99). There was no publication bias as evaluated by the funnel plot and Egger’s regression asymmetry test with p = 0.62 and p = 0.17 for the incidence of AKI and severe AKI requiring RRT, respectively. Conclusion: Among patients receiving ECMO, the incidence rates of AKI and severe AKI requiring RRT are high, which has not changed over time. Patients who develop AKI requiring RRT while on ECMO carry 3.7-fold higher hospital mortality.

Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. Methods: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). Results: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8–13.4%, I2 = 0%) and 5.5% (95%CI: 2.9–10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6–34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2–36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger’s regression asymmetry test (p > 0.05 for all analyses). Conclusions: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS.

Abstract Minimally invasive transcatheter embolization is a common nonsurgical procedure in interventional radiology used for the deliberate occlusion of blood vessels for the treatment of diseased or injured vasculature. A wide variety of embolic agents including metallic coils, calibrated microspheres, and liquids are available for clinical practice. Additionally, advances in biomaterials, such as shape‐memory foams, biodegradable polymers, and in situ gelling solutions have led to the development of novel preclinical embolic agents. The aim here is to provide a comprehensive overview of current and emerging technologies in endovascular embolization with respect to devices, materials, mechanisms, and design guidelines. Limitations and challenges in embolic materials are also discussed to promote advancement in the field.

e14237 Background: Targeting myeloid-derived suppressor cells (MDSCs), key mediators of intrinsic and adaptive immune resistance, remains a significant challenge in kidney cancer immunotherapy. One potential driver of MDSC mediated tumor immunosuppression is the cytokine interleukin-1 beta (IL-1β). Although large cancer prevention studies show that targeting IL1 decreases cancer risk, the exact mechanism of anti-IL-1 mediated anti-tumor efficacy is not yet defined. To understand the immunogenic effects of IL-1β blockade and effects on MDSCs, we used the RENCA model of RCC. Methods: We inoculated BALB/c mice with 1x106 RENCA cells. On Day +10 we treated mice (n = 8/group) with vehicle, αPD1, αIL1β, cabozantinib, combination αPD1/αIL1β, or cabozantinib/αIL1β. We harvested day +18 tumors to quantify tumor size and immune cells by flow cytometry. We then isolated immune cells for differential gene expression profiling by RNAseq. Results: Treatment with αIL1β significantly decreased tumor size compared to vehicle or αPD1 monotherapy. Combining αPD1/αIL1β or cabozantinib/αIL1β potentiated the anti-tumor effects of αPD1 or cabozantinib monotherapy respectively. Anti-IL1β therapy decreased polymorphonuclear (PMN)-MDSC infiltration (αIL1β: 0.76% +/- 0.21 vs. vehicle: 1.89% +/- 0.37, P = 0.014). Relative to PD1 monotherapy, combining αPD1 and αIL1β decreased PMN-MDSCs (αPD1: 2.14% +/- 0.56 vs αPD1/αIL1β: 0.91% +/- 0.15, P = 0.033) and increased M1-like tumor associated macrophages (TAM) (αPD1: 0.798% +/- 0.21 vs. αPD1/αIL1β: 12.04% +/- 2.9, P = 0.0008). Gene expression profiling from sorted immune cells from αIL1β treated tumors revealed multiple differentially regulated cytokines including interleukin-6, IFN-γ, and IL-10. Conclusions: Blockade of IL-1β depletes intratumoral PMN-MDSCs and increases M1-like TAM with minimal effects observed on the T cell compartment. Treatment with cabozantinib or αPD1 in combination with αIL1β led to sustained control of tumor growth. IL-1β represents a promising target for kidney cancer immunotherapy. Based on the preclinical data, a clinical trial of neoadjuvant αPD1 and αIL1β therapy is planned for patients with high risk RCC.

ABSTRACTAimThis study aimed to assess the relationship between admission Calcium‐phosphate (CaP) and in‐hospital mortality in hospitalized patients.MethodsAll adult hospitalized patients who had both admission serum calcium and phosphate levels available between years 2009 and 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<21, 21–<27, 27–<33, 33 39, 39–<45 and ≥45 mg2/dL2). Multivariate logistic regression was used to assess the association between admission CaP and in‐hospital mortality, using the CaP of 27–<33 mg2/dL2 as the reference group.ResultsAbut 14 772 patients were included in the analysis. The association between CaP and in‐hospital mortality was U‐shaped with the lowest in‐hospital mortality in CaP of 27–<33 mg2/dL2. After adjusting for potential confounders, both CaP <21 and ≥39 mg2/dL2 were associated with higher in‐hospital mortality. Subgroup analysis demonstrated that the highest in‐hospital mortality risk in both chronic kidney disease (CKD) and non‐CKD patients occurred when CaP ≥ 45 mg2/dL2.ConclusionCaP levels on admission were associated with in‐hospital mortality. Highest mortality risk was observed in hospitalized patients with admission CaP of ≥45 mg2/dL2 in both CKD and non‐CKD patients.

Introduction Significant tricuspid regurgitation is a well recognized indicator of right ventricular dysfunction. Recent studies have shown that significant tricuspid regurgitation is potentially associated with increased mortality in patients with severe aortic stenosis who underwent transcatheter aortic valve replacement (TAVR). However, data remained sparse and inconclusive. Thus, we performed a systematic review and meta-analysis of the literature to assess the association between significant tricuspid regurgitation and mortality in post TAVR patients. Hypothesis Significant tricuspid regurgitation is predictive for higher mortality in patients undergoing TAVR. Methods We comprehensively searched the databases of MEDLINE and EMBASE from inception to October 2018. Included studies were published observational studies that reported multivariate analysis of the effects of significant tricuspid regurgitation on all-cause mortality among patients undergoing TAVR. Data from each study were combined utilizing the random-effects, generic inverse variance method of DerSimonian and Laird to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Results Nine cohort studies from August 2011 to May 2018 consisting of 27 614 patients with severe aortic stenosis undergoing TAVR (6255 with and 21 359 without significant tricuspid regurgitation) were included in this meta-analysis. The presence of significant tricuspid regurgitation was associated with higher all-cause mortality (pooled OR = 2.26, 95% CI: 1.45–3.52, P < 0.001). We found that all-cause mortality remained statistically substantial in all subgroups (30-day all-cause mortality: OR = 2.05, 95% CI: 1.20–3.49, P = 0.009; midterm all-cause mortality: OR = 9.67, 95% CI: 2.44–38.31, P = 0.001; and long-term all-cause mortality: OR = 1.48, 95% CI: 1.19–1.85, P < 0.001). Funnel plots and Egger's regression asymmetry test were performed and showed no publication bias. Conclusion Significant tricuspid regurgitation increased risk of mortality by up to two-fold among patients with severe aortic stenosis undergoing TAVR. Our study suggests that significant tricuspid regurgitation should be considered a component of risk stratification tools.