41-Year-Old Male with Sub-Acute Encephalopathy, Seizures, and End Stage Renal Disease: A Unifying Diagnosis and Response to Therapy.

We describe a case of a 41-year-old male with a history of end-stage renal disease, hypertension, epilepsy, ischemic stroke, and traumatic brain injury transferred to our tertiary care center for subacute, progressive cognitive impairment. He was found to have disproportionate brain atrophy, focal seizures, and refractory hypertension. Given suspicion for an underlying genetic etiology, a genetic panel for progressive renal disease was sent, revealing two known pathogenic variants in a gene for a cobalamin metabolism disorder, Cobalamin C deficiency. He was started on targeted metabolic supplementation with subsequent improvement in his cognition. Our case highlights the crucial need to expand diagnostic workup to include genetic and metabolic causes in patients with neurologic disease, atypical features, relevant family history and multi-organ dysfunction.

Association Between a Common, Benign Genotype and Unnecessary Bone Marrow Biopsies Among African American Patients.

Importance: Up to two-thirds of African American individuals carry the benign rs2814778-CC genotype that lowers total white blood cell (WBC) count. Objective: To examine whether the rs2814778-CC genotype is associated with an increased likelihood of receiving a bone marrow biopsy (BMB) for an isolated low WBC count. Design, Setting, and Participants: This retrospective genetic association study assessed African American patients younger than 90 years who underwent a BMB at Vanderbilt University Medical Center, Mount Sinai Health System, or Children's Hospital of Philadelphia from January 1, 1998, to December 31, 2020. Exposure: The rs2814778-CC genotype. Main Outcomes and Measures: The proportion of individuals with the CC genotype who underwent BMB for an isolated low WBC count and had a normal biopsy result compared with the proportion of individuals with the CC genotype who underwent BMB for other indications and had a normal biopsy result. Results: Among 399 individuals who underwent a BMB (mean [SD] age, 41.8 [22.5] years, 234 [59%] female), 277 (69%) had the CC genotype. A total of 35 patients (9%) had clinical histories of isolated low WBC counts, and 364 (91%) had other histories. Of those with a clinical history of isolated low WBC count, 34 of 35 (97%) had the CC genotype vs 243 of 364 (67%) of those without a low WBC count history. Among those with the CC genotype, 33 of 34 (97%) had normal results for biopsies performed for isolated low WBC counts compared with 134 of 243 individuals (55%) with biopsies performed for other histories (P < .001). Conclusions and Relevance: In this genetic association study, among patients of African American race who had a BMB with a clinical history of isolated low WBC counts, the rs2814778-CC genotype was highly prevalent, and 97% of these BMBs identified no hematologic abnormality. Accounting for the rs2814778-CC genotype in clinical decision-making could avoid unnecessary BMB procedures.

Erythropoietin in Lupus: Unanticipated Immune Modulating Effects of a Kidney Hormone.

Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease with variable clinical presentation, typically characterized by a relapsing-remitting course. SLE has a multifactorial pathogenesis including genetic, environmental, and hormonal factors that lead to loss of tolerance against self-antigens and autoantibody production. Mortality in SLE patients remains significantly higher than in the general population, in part because of the limited efficacy of available treatments and the associated toxicities. Therefore, novel targeted therapies are urgently needed to improve the outcomes of affected individuals. Erythropoietin (EPO), a kidney-produced hormone that promotes red blood cell production in response to hypoxia, has lately been shown to also possess non-erythropoietic properties, including immunomodulatory effects. In various models of autoimmune diseases, EPO limits cell apoptosis and favors cell clearance, while reducing proinflammatory cytokines and promoting the induction of regulatory T cells. Notably, EPO has been shown to reduce autoimmune response and decrease disease severity in mouse models of SLE. Herein, we review EPO's non-erythropoietic effects, with a special focus on immune modulating effects in SLE and its potential clinical utility.

Urine Microscopy for Internal Medicine Residents: A Needs Assessment and Implementation of Virtual Teaching Sessions.

Background: Although urine microscopy is an important step in the initial evaluation of a patient with kidney disease, internal medicine residents have minimal exposure to this technique during their training. The goal of this study was to understand knowledge of and attitudes toward urine microscopy among internal medicine residents and to implement virtual urine microscopy teaching sessions. Methods: A voluntary, anonymous, online survey was sent to all of the categorical internal medicine residents (n=131) training at the Icahn School of Medicine at Mount Sinai (ISMMS). The survey included 13 questions to assess attitudes toward, experience with, and clinical interpretation of urine microscopy specimens. In response to the survey results, we implemented virtual urine microscopy teaching sessions using video conferencing software that incorporated real-time urine sediment analysis with nephrology fellows and attending nephrologists. Results: The survey response rate was 45% (59 of 131). Forty-seven percent (28 of 59) of respondents reported performing urine microscopy at least once during their training, and 75% (44 of 59) of respondents did not feel comfortable performing urine microscopy. The majority of residents (92%; 54 of 59) reported they felt urine microscopy was very helpful or somewhat helpful in the evaluation of patients with AKI. Overall, 41% of responses to clinical interpretation questions were considered correct. Following survey completion, virtual urine microscopy sessions were held monthly and well received by the participants. Conclusions: Our study found that internal medicine residents perceive urine microscopy as a helpful diagnostic tool, although lack the skills to perform and interpret urine microscopy sediments. Virtual educational sessions using video conferencing software are a technically feasible approach to teaching urine microscopy to internal medicine residents. Future studies include a study of the effect of these sessions on learning of urine microscopy. Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/K360/2021_01_28_KID0006282020.mp3.

Renal Cell Cancer and Chronic Kidney Disease.

The association between chronic kidney disease (CKD) and renal cell carcinoma (RCC) is bidirectional and multifactorial. Risk factors such as hypertension, diabetes mellitus, obesity, and smoking increase the risk of both CKD and RCC. CKD can lead to RCC via an underlying cystic disease or oxidative stress. RCC can cause CKD because of the tumor itself, surgical reduction of renal mass (either partial or radical nephrectomy), and perioperative acute kidney injury. Medical therapies such as immune checkpoint inhibitors and vascular endothelial growth factor inhibitors can lead to acute kidney injury and resultant CKD. Clinicians need to be aware of the complex, bidirectional interplay between both diseases.

Chronic Kidney Disease in Cancer Survivors.

As breakthroughs in cancer care are leading to improved long-term outcomes in a subset of advanced cancers, there is a growing population of long-term cancer survivors that are at risk of long-term complications. In this review, we summarize what is known about chronic kidney disease in cancer survivors, focusing on the following high-risk groups: survivors of childhood cancers, stem cell transplant recipients, patients with renal cell carcinoma, patients exposed to cisplatin and other nephrotoxic chemotherapies, and patients receiving immunotherapy for cancer. As new anticancer therapies are developed, more research is needed to understand the long-term risks of kidney function decline and to devise methods to prevent chronic kidney disease.

Addressing the need for forensic psychological evaluations of asylum seekers: The potential role of the general practitioner.

Asylum seekers who have survived torture and other abuses may experience a wide range of psychological symptoms associated with depression, anxiety, and posttraumatic stress disorder. During the asylum process, attorneys might refer their clients to clinicians who document these psychological sequelae of human rights violations. However, the need for forensic psychological evaluations exceeds the number of mental health clinicians available to provide these assessments. It has been suggested that primary care physicians, professionals who already play essential roles in the identification and treatment of mental health issues, may be able to conduct these evaluations. Yet, there is little empirical knowledge of what prior training and clinical experiences support mental health and non-mental health professionals who engage in this work, and what is needed to prepare general practitioners to provide forensic psychological evaluations to asylum seekers. This pilot study found non-mental health practitioners with experience in psychological forensic evaluations reached a level of confidence in conducting evaluations of asylum seekers comparable to general mental health practitioners. The study also identified clinicians' perceptions of training that supports them in their forensic psychological evaluations, their professional development needs, and the potential for general practitioners to leverage their current skill sets in this work.

Defining the utility of anteroposterior venography in the diagnosis of venous iliofemoral obstruction.

BACKGROUND: Intravascular ultrasound (IVUS) is the current standard for the diagnosis of obstruction in the iliac and femoral veins. However, multiple venographic findings including collaterals, pancaking, and contrast thinning have been suggested to improve the sensitivity of venography. The objective of our study was to further elucidate where and how anteroposterior venography may successfully guide the diagnosis of venous obstruction. METHODS: A retrospective review of patients with chronic venous insufficiency who received iliofemoral stenting by a single practitioner at a tertiary medical center between January 2014 and August 2016 was performed. Patients who had records of anteroposterior venography and IVUS were included. Patients who underwent reoperation, did not have complete records of venography and IVUS, or had preoperative acute deep vein thrombosis were excluded. All patients with a greater than 50% luminal area reduction by IVUS underwent balloon angioplasty and stent placement. The locations of stenosis, collaterals, pancaking, and contrast thinning with venography, the locations of stenosis with IVUS, and the location of each stent placed were recorded. RESULTS: There were 107 patients who underwent venous stenting guided by venography and IVUS in this study. Six patients who underwent reoperation, 1 patient who had an acute preoperative deep vein thrombosis, and 14 patients who had incomplete records were excluded. Thus, 86 patients with 77 left lower extremity and 68 right lower extremity studies were available for analysis. The sensitivity by stenosis on venography was 4% in the left common iliac vein (CIV), 44% in the left external iliac vein (EIV), and 44% in the common femoral vein (CFV). The sensitivity by stenosis on venography in the right CIV, EIV, and CFV was 21%, 46%, and 40%, respectively. Combined, pancaking and collaterals had a sensitivity of 97% in the left CIV. IVUS resulted in a change in plan in 2%, 32%, and 48% of patients in the left CIV, EIV, and CFV, and in 26%, 35%, and 48% of patients in the right CIV, EIV, and CFV, respectively. CONCLUSIONS: Anteroposterior venography can indirectly diagnose obstruction of the left CIV through the identification of collaterals and pancaking. The combination of low sensitivity and a high rate of change of plan owing to IVUS precludes complete reliance on anteroposterior venography for the diagnosis of lesions in the left EIV and CFV and the right CIV, EIV, and CFV. IVUS must be used to comprehensively identify all venous iliofemoral lesions.

Inflammation as a predictor of disease course in posttraumatic stress disorder and depression: A prospective analysis from the Mind Your Heart Study.

BACKGROUND: Prior research has focused largely on the pro-inflammatory states of PTSD and depression, with few studies evaluating the direction of inflammation's association with these disorders. To clarify whether inflammation plays a role in the development of PTSD or depression, we assessed the predictive value of inflammatory biomarkers on the courses of these conditions in a cohort of Veterans. METHODS: This research was part of the Mind Your Heart Study, a prospective cohort study designed to examine PTSD-related health outcomes. Between 2008 and 2010, 746 San Francisco area Veterans Administration patients were enrolled. At baseline, inflammatory biomarkers were measured from fasting morning venous blood draws, and cortisol and catecholamine levels were measured from 24-hour urine samples. PTSD was diagnosed using the PTSD Checklist at baseline and annual follow-up. Depression was evaluated using the 9-item Patient Health Questionnaire at baseline and follow-up. Ordinal logistic regression models were used to assess the predictive value of baseline biomarker levels on clinically relevant courses of PTSD and depression categorized and ordered as none, resolved, developed, and chronic. RESULTS: After adjustment for age and sex, elevated levels of white blood cell count (OR = 1.27(1.10-1.47), p = 0.001), C-reactive protein (OR = 1.20(1.04-1.39), p = 0.02), fibrinogen (OR = 1.19(1.03-1.38), p = 0.02), and ESR (OR = 1.17(1.00-1.36, p = 0.05), and decreased levels of urine cortisol (OR = 0.84(0.71-0.99), p = 0.04) were significant predictors of poorer courses of PTSD. Elevated levels of WBC count (OR = 1.31(1.14-1.50), p < 0.001), CRP (OR = 1.24(1.07-1.43), p = 0.003), fibrinogen (OR = 1.26(1.09-1.46), p = 0.002), and catecholamines (OR = 1.17(1.01-1.36), p = 0.04) were significant predictors of poorer courses of depression. After additionally controlling for physical activity, elevated WBC count (p = 0.002) and decreased levels of urine cortisol (p = 0.05) remained significant predictors of PTSD course, and elevated WBC count (p = 0.001), CRP (p = 0.03), and fibrinogen (p = 0.02) remained significant predictors of depression course. After adjusting for all significant variables, elevated WBC count (p = 0.02) was a significant predictor of a poorer course of PTSD, and elevated WBC count (p = 0.04) and platelet count (p = 0.03) were significant predictors of a poorer course of depression. CONCLUSIONS: Increased levels of several inflammatory biomarkers were associated with significantly increased odds of clinically worse courses of PTSD and depression. Inflammation may be a target for prevention and treatment of these mental health disorders.

Intrahost Selection Pressures Drive Rapid Dengue Virus Microevolution in Acute Human Infections.

Dengue, caused by four dengue virus serotypes (DENV-1 to DENV-4), is a highly prevalent mosquito-borne viral disease in humans. Yet, selection pressures driving DENV microevolution within human hosts (intrahost) remain unknown. We employed a whole-genome segmented amplification approach coupled with deep sequencing to profile DENV-3 intrahost diversity in peripheral blood mononuclear cell (PBMC) and plasma samples from 77 dengue patients. DENV-3 intrahost diversity appears to be driven by immune pressures as well as replicative success in PBMCs and potentially other replication sites. Hotspots for intrahost variation were detected in 59%-78% of patients in the viral Envelope and pre-Membrane/Membrane proteins, which together form the virion surface. Dominant variants at the hotspots arose via convergent microevolution, appear to be immune-escape variants, and were evolutionarily constrained at the macro level due to viral replication defects. Dengue is thus an example of an acute infection in which selection pressures within infected individuals drive rapid intrahost virus microevolution.

Chikungunya Virus Sequences Across the First Epidemic in Nicaragua, 2014-2015.

Chikungunya is caused by the mosquito-borne arthrogenic alphavirus, chikungunya virus (CHIKV). Chikungunya was introduced into the Americas in late 2013 and Nicaragua in mid-2014. Here, we sequenced five imported and 30 autochthonous Nicaraguan CHIKV from cases identified in the first epidemic in the country between August 2014 and April 2015. One full-length and two partial genomic sequences were obtained by deep sequencing; Sanger methodology yielded 33 E1 sequences from five imported and 28 autochthonous cases. Phylogenetic analysis indicates that Nicaraguan CHIKV all belonged to the Asian genotype, Caribbean clade. Moreover, E1 gene sequences revealed accumulation of mutations in later months of the epidemic, including four silent mutations in 11 autochthonous cases and three non-synonymous mutations in three autochthonous cases. No mutations contributing to increased transmissibility by Aedes albopictus were identified in the E1 gene. This represents the most comprehensive set of CHIKV sequences available from the Americas to date.