Diabetic Ketoacidosis and Acute Kidney Injury Associated With Enfortumab Vedotin for Urothelial Carcinoma: A Case Report.

Enfortumab vedotin is a novel breakthrough therapy that received accelerated US Food and Drug Administration approval in 2019 for the treatment of metastatic urothelial carcinoma in patients who have failed other lines of treatment. The characteristics of its adverse effects are not well understood. Diabetic ketoacidosis has been reported in 2 postmarketing reports presented as abstracts at the 2020 American Thoracic Society Conference and the 2021 American Society of Nephrology Conference. Both cases progressed rapidly and expired in <3 days. We present a similar case of a man in his late 50s with no history of diabetes who was diagnosed with urothelial carcinoma 2 years prior. Despite several lines of treatment, including platinum-based chemotherapy and immune checkpoint inhibitors, he developed metastasis and was started on enfortumab vedotin. After his second dose of enfortumab vedotin, he was admitted to the intensive care unit for diabetic ketoacidosis with an initial A1C level of 7.7%. He was intubated for airway protection, started on pressors, and developed oliguric acute kidney injury requiring continuous venovenous hemodialysis. Despite aggressive treatment, the patient died on hospital day 2. The lethality of this aggressive diabetic ketoacidosis despite therapy suggests some other effect of enfortumab vedotin on glucose metabolism in addition to insulin resistance and the need for prior diabetes screening.

Kidney disease and COVID-19 disease severity-systematic review and meta-analysis.

We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.

Pulmonary embolism in chronic kidney disease and end-stage renal disease hospitalizations: Trends, outcomes, and predictors of mortality in the United States.

BACKGROUND: It is well-known that patients with chronic kidney disease and end-stage renal disease are at increased risk of pulmonary embolism than patients with normal kidney function. However, the data on trends, outcomes, and predictors of mortality in pulmonary embolism patients with chronic kidney disease and end-stage renal disease in the United States are limited. METHODS: We queried the National Inpatient Sample database from 2010 to 2014. International Classification of Diseases-Ninth Revision-Clinical Modification codes were used to identify patients with normal kidney function, chronic kidney disease, and end-stage renal disease. The frequency of pulmonary embolism, complications, in-hospital mortality, and length of stay were calculated for each cohort. Multivariable logistic regression models were constructed to determine the predictors of mortality. RESULTS: In the study population (2010-2014), there were 766,176 pulmonary embolism hospitalizations with normal kidney function, 79,824 with chronic kidney disease, and 9147 with end-stage renal disease. Among the study cohorts, the mortality rate was 2.7% in normal kidney function, 4.5% in chronic kidney disease, and 6.8% in end-stage renal disease hospitalizations. Median length of stay was highest in the end-stage renal disease cohort and lowest in the normal kidney function cohort. After adjusting for confounders, pulmonary embolism patients with chronic kidney disease died 1.15 times more often than those with normal kidney function and pulmonary embolism patients with end-stage renal disease died 4.2 times more often than those with normal kidney function. CONCLUSION: The mortality rate and length of stay in pulmonary embolism patients with chronic kidney disease and end-stage renal disease were significantly higher than those in pulmonary embolism patients with normal kidney function. Also, pulmonary embolism patients with chronic kidney disease and end-stage renal disease were at higher risk of in-hospital mortality than those with normal kidney function. There was statistically significant higher risk of mortality in elderly and Black patients with pulmonary embolism and concurrent chronic kidney disease or end-stage renal disease.

Uremic- and Dialysis-Associated Pericarditis.

Uremic pericarditis occurs as a result of inflammation of the pericardium due to toxins and immune complexes in patients with renal disease. The initial clinical manifestations of pericarditis and acute coronary syndrome may be similar, and initial EKG findings may overlap. The management of this disease needs the combined efforts of internists, cardiologists, and nephrologists. Its incidence has been reduced since the introduction of renal replacement therapy. Dialysis continues to be the mainstay of treatment.

Trends and outcomes of venous thromboembolism in adult hospitalizations with acute myeloid leukemia: analysis of nationwide inpatient sample from 2010 to 2014.

Background: Venous thromboembolism (VTE) occurs frequently in acute myeloid leukemia (AML) patients. There are no population-based studies from the United States (U.S.) analyzing this association. The study aims to analyze the trends, predictors of mortality, and outcomes of VTE in AML patients.Methods: We analyzed the publicly available Nationwide Inpatient Sample (NIS) for years 2010-2014. Hospitalizations due to AML were identified by previously validated International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes as the primary diagnosis. VTE was identified by ICD-9-CM codes as secondary diagnosis. Hospitalizations with age less than 18 years of age were excluded. The trends and outcomes were determined using Chi-squared (χ2) test and multivariate regression models.Results: From 2010 to 2014, there were 313,282 hospitalizations with a primary diagnosis of AML and 1,633 hospitalizations (0.1%) had VTE as a concurrent diagnosis. There was a significant increase in the proportion of AML hospitalizations with VTE from 0.47% in 2010 to 0.56% in 2014 (P = 0.014). Multivariable regression analysis showed that the odds of in-hospital mortality were not higher in AML hospitalizations with VTE (odds ratio [OR] 1.11; 95% confidence interval [CI] 0.81-1.52; P = 0.5) than those without VTE. Age group above 84 years carried the highest risk of mortality (OR 3.20; 95% CI 2.77-3.70; P < 0.0001) in AML-VTE patients. Black (OR 1.23; 95% CI 1.13-1.35; P < 0.0001) and uninsured patients (OR 1.50; 95% CI 1.31-1.73; P < 0.0001) were at significantly higher odds of in-hospital mortality amongst the AML-VTE hospitalizations.Conclusion: The proportion of AML hospitalizations with VTE continues to rise in the U.S. After adjusting for confounders, increasing age, Black race, and lack of insurance were found to have higher risk of in-hospital mortality in the AML-VTE cohort. The odds of in-hospital mortality in AML hospitalizations with VTE are not higher than those without VTE.

Dieulafoy's Lesion: Decade-Long Trends in Hospitalizations, Demographic Disparity, and Outcomes.

Background Dieulafoy's lesion is a relatively rare, but potentially life-threatening, condition where a tortuous arteriole, most commonly in the stomach, may bleed and lead to significant gastrointestinal hemorrhage. Limited epidemiological data exist on patient characteristics and the annual number of hospitalizations associated with such lesions. The aim of our study is to determine the inpatient burden of Dieulafoy's lesion. Methods We analyzed the National Inpatient Sample (NIS) database for all subjects with a discharge diagnosis of Dieulafoy's lesion of the stomach, duodenum, and colon using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes 537.84 and 569.86 as the primary or secondary diagnosis during the period from 2002 to 2011. Statistical significance of variation in the number of hospital discharges and demographics during the study period was achieved using the Cochrane-Armitage trend test. Results In 2002, there were 1,071 admissions with a discharge diagnosis of Dieulafoy's lesion as compared to 7,414 in 2011 (p < 0.0001). Dieulafoy's lesion was found to be most common in the age group of 65-79 years (p < 0.0001). Overall, it was found to be more common in males as compared to females (p = 0.0261). The white race was most commonly affected amongst all the races. The average cost of care per hospitalization increased from $14,992 in 2002 to $25,594 in 2011 (p < 0.0001). Conclusion There has been a steady rise in the number of inpatient admissions with Dieulafoy's lesions. Advances in diagnostic techniques likely play a key role in the higher detection rates along with the possible involvement of other unknown factors. Men, in the age group of 65 to 79 years, and Whites were found to have significantly higher admission rates than all other groups, with a significant increase in the cost of care.

Telemedicine, the current COVID-19 pandemic and the future: a narrative review and perspectives moving forward in the USA.

A narrative review was conducted to examine the current state of the utilisation of telemedicine amid the current COVID-19 pandemic and to evaluate the benefits of continuing telemedicine usage in the future. A literature review was performed for articles related to telemedicine. Databases including PubMed, Google Scholar, Cochrane Library and Ovid MEDLINE were searched. Three reviewers independently performed article selection based on relevance to our topic. We included all articles between 1990 and 2020 related to telemedicine using the following keywords: 'telemedicine', 'telehealth', 'policy', 'COVID-19', 'regulation', 'rural', 'physical examination', 'future'. A total of 60 articles were identified, and through careful selection we narrowed the final number of articles to 42 based on relevance to our topic. Telemedicine has been rapidly evolving over the past several decades. Issues with regulation and reimbursement have prevented its full immersion into the healthcare system. During the current pandemic, Centers for Medicare and Medicaid services have expanded access to telemedicine services. The advantages of telemedicine moving forward include its cost-effectiveness, ability to extend access to specialty services and its potential to help mitigate the looming physician shortage. Disadvantages include lack of available technological resources in certain parts of the country, issues with security of patient data, and challenges in performing the traditional patient examination. It is critically important that changes are made to fully immerse telemedicine services into the healthcare landscape in order to be prepared for future pandemics as well as to reap the benefits of this service in the future.

FDG-PET Versus PSMA-PET: A Patient With Prostate Cancer.

A 64-year old male presented to the hospital with a 1-week history of stools with bright red blood. Subsequent colonoscopy with a biopsy revealed a low-lying, moderately differentiated, rectal adenocarcinoma. A pelvic magnetic resonance imaging done afterwards showed a possible T3N1 rectal cancer with intact muscularis mucosa and a singular presacral lymph node enlargement. Furthermore, a suspicious peripheral prostatic enlargement and a possible left iliac crest sclerotic bone lesion were incidentally identified. 18F-FDG (fluorodeoxyglucose) PET (positron emission tomography) scan confirmed a primary FDG avid rectal tumor and a presacral lymph node; however, there was no prostate or iliac crest uptake. A serum prostate-specific antigen performed in the hospital returned with a value of 37 ng/mL, which prompted a prostate biopsy, eventually returning as positive for adenocarcinoma. Consequently, a 68Ga-PSMA PET scan to rule out possible metastatic prostate disease revealed increased PSMA expression in the prostate only. After consultation with the radiologist and nuclear medicine physician who concluded the iliac crest lesion is likely not cancerous, the final diagnosis of T3N1 rectal cancer with simultaneous high-grade prostate adenocarcinoma was declared. This case highlights the low sensitivity of 18F-FDG PET scans for prostate cancer, the need for routine serum prostate-specific antigen screening, and the progression of 68Ga-PSMA PET as a diagnostic tool for prostate cancer.

Gastrointestinal Hemorrhage in Acute Kidney Injury Patients on Hemodialysis.

Background Gastrointestinal bleeding (GIB) has been reported to be more common in patients with chronic renal failure and end-stage renal disease requiring hemodialysis with higher mortality than in the general population. Limited epidemiological data exist on the annual number of hospitalizations, demographic variation, cost of care, and outcomes for GIB in patients with acute kidney injury (AKI) requiring and not requiring hemodialysis (HD). The main objective of this study was to analyze the trends of GIB in patients with AKI requiring HD and those not requiring HD during hospitalization. Methods and Results We analyzed the National (Nationwide) Inpatient Sample (NIS) database for all subjects with a discharge diagnosis of AKI as the primary or secondary diagnosis during the period from 2001 to 2011. Subjects with a discharge diagnosis of hemodialysis and GIB were then identified from the pool and trends were analyzed. A significant rise in the annual number of hospitalizations with AKI was found with a greater proportion being discharged without HD. From 2001 to 2011, there were 19,393,811 hospitalizations with a discharge diagnosis of AKI of which 1,424,692 (7.3%) received HD (HD group), whereas 17,969,119 (92.7%) did not receive HD (non-HD group) (p < 0.0001). The male gender was more commonly affected by GIB than the female gender in both groups (p < 0.0001). The cost of care per hospitalization for GIB patients in the HD group increased over the study period with average found to be $61,463 (adjusted for inflation, p < 0.0001), whereas for GIB patients in the non-HD group, it showed a slight decrease in trend with the average found to be $28,419 (p < 0.0001). All-cause mortality was higher for GIB patients in the HD group (38.1%) than in the non-HD group (25.1%) (p < 0.0001). Conclusions GIB is more common and associated with higher all-cause inpatient mortality in patients receiving HD in comparison to non-HD patients.

Tenofovir and Severe Symptomatic Hypophosphatemia.

Tenofovir is a broadly used drug used for the treatment of human immunodeficiency virus (HIV). Although the initial results of the clinical trials supported the renal safety of Tenofovir, clinical use of it has caused a low, albeit a significant, risk of renal damage either in the form of AKI or CKD. The pathophysiology has been linked to the effect of this medication on the proximal tubular cell. Although the exact mechanism is unknown, studies have suggested that Tenofovir accumulates in proximal tubular cells which are rich in mitochondria. It is both filtered in the glomerulus and actively secreted in the tubules for elimination and is excreted unchanged in the urine. Studies have shown an active transportation of 20-30% of this drug into the renal proximal tubule (PCT) cells via the organic anion transporters in the baso-lateral membrane (primarily hOAT1, and OAT3 to a lesser extent) and ultimate excretion of the drug into the tubular lumen via the transporters in the proximal tubular apical membrane MRP4 and MRP2 (multidrug resistance-associated proteins 2 & 4). Subsequently, the mitochondrial injury caused by Tenofovir can lead to the development of Fanconi's syndrome which causes renal tubular acidosis, phosphaturia, aminoaciduria, glucosuria with normoglycemia, and tubular proteinuria. Here we present a case where Tenofovir treatment resulted in severe hypophosphatemia requiring hospitalization for parentral phosphate repletion.

Atypical Hemolytic Uremic Syndrome Presenting as Acute Heart Failure-A Rare Presentation: Diagnosis Supported by Skin Biopsy.

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder of uncontrolled complement activation that manifests classically as anemia, thrombocytopenia, and renal failure, although extrarenal manifestations are observed in 20% of the patient most of which involving central nervous system, with relatively rare involvement of the heart. In this article, we report the case of a 24-year-old male with no history of heart disease presenting with acute systolic heart failure along with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given his presentation of thrombotic microangiopathy (TMA), along with laboratory results significant for low haptoglobin, platelets, hemoglobin, C3, C4, CH50, and normal ADAMTS13 levels, with no diarrhea and negative STEC polymerase chain reaction in stool, aHUS diagnosis was established with strong clinical suspicion, and immediate initiation of treatment was advised. Kidney biopsy to confirm diagnosis of aHUS was inadvisable because of thrombocytopenia, so the skin biopsy of a rash on his arm was done, which came to be consistent with thrombotic microangiopathy. Our case highlights a relatively rare association between aHUS and cardiac involvement, and the use of skin biopsy to support diagnosis of aHUS in patients who cannot undergo renal biopsy because of thrombocytopenia.

Dosing of radioactive iodine in end-stage renal disease patient with thyroid cancer.

We describe detailed administration of thyroidal and extrathyroidal doses of radioiodine to a patient with end-stage renal disease on hemodialysis. A thorough description of area under curve measurements in a patient with compromised renal function has rarely been described in the literature. Few publications have described thyroid cancer management of patients on hemodialysis, and we believe our management will aid in patient treatment in the future. LEARNING POINTS: Scheduling of hemodialysis is important when administering radioactive iodine.Treatment of thyroid cancer with radioiodine in patients with end-stage renal disease requires multidisciplinary approach coordinating dialysis, nuclear medicine and endocrinologists care.Balancing ideal dosage of I131 and the timing of dialysis to insure maximal thyroidal uptake and minimal extra thyroidal I131 concentration is necessary.

Multiple Myeloma as the Underlying Cause of Thrombotic Microangiopathy Leading to Acute Kidney Injury: Revisiting a Very Rare Entity.

Thrombotic microangiopathy (TMA) describes a pathological process of microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia, leading to end-organ ischemia and infarction, affecting particularly the kidney and brain. TMA is a pathological feature of a number of clinical disorders including thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and atypical hemolytic uremic syndrome. Rare but important, TMA may also occur in malignancy, connective tissue disease, malignant hypertension, and renal transplantation (rejection or drug toxicity). We present a very rare case where the patient developed acute kidney injury from TMA but found to have multiple myeloma as the possible underlying etiology.

Thrombotic microangiopathy associated with synthetic cannabinoid receptor agonists.

Marijuana is one of the most commonly used recreational drugs in the United States. As marijuana is illegal in the majority of countries, the use of readily available and unregulated synthetic cannabinoids (SCBs) has increased. Little is known about the potential adverse effects of SCBs especially in regards to their nephrotoxicity. Case reports of acute kidney injury (AKI) from acute tubular injury secondary to their use have been reported. However, the exact pathology, mechanism, and extent of renal injury remain unknown. We report the first case of biopsy proven thrombotic microangiopathy (TMA) associated with SCBs resulting in AKI. The patient suffered significant morbidity with loss of renal function eventually requiring renal replacement therapy.

Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome is a rare disorder which is known to cause acute thrombotic microangiopathy during pregnancy with poor maternal and fetal outcomes. Atypical hemolytic uremic syndrome is caused mostly by dysregulation of alternative complement pathway secondary to genetic mutations. Most of the cases reported have been in the post-partum period. We report a rare case of a patient who presents with thrombotic microangiopathy in the first trimester of her eleventh pregnancy and was successfully treated with eculizumab. CASE PRESENTATION: A 30-year-old woman presented at 10 weeks of gestation with hypertension, hemolytic anemia, thrombocytopenia, and acute kidney injury, consistent with thrombotic microangiopathy. She was managed initially with daily plasmapheresis. However, her kidney function did not recover, requiring hemodialysis. ADAMTS13 activity was later found to be within normal limit, hence diagnosis of atypical hemolytic uremic syndrome was strongly considered at that time and she was immediately treated with anti-C5 humanized monoclonal antibody (eculizumab). The patient responded well (resolution of thrombotic microangiopathy and recovery of renal function) to eculizumab, with continued remission after discharge and successfully delivered a healthy baby at term without any peripartum complications. CONCLUSION: Early recognition of atypical hemolytic uremic syndrome is often difficult as several other conditions also manifest as thrombotic microangiopathy during pregnancy, causing delay in initiating appropriate treatment. Our case suggests that treatment of atypical hemolytic uremic syndrome in early trimester of pregnancy with eculizumab results in good outcome to mother and fetus.

Type B Lactic Acidosis Associated With Venlafaxine Overdose.

Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug.

Electronic Capture of Written Handoff Information: What Are the Next Steps?

Communication lapses during patient care transitions are reported to be frequent and may result in patient harm. The primary objective of our study was to assess the completeness, accuracy, and usefulness of our electronic handoff system to guide future software changes and educational interventions. We randomly selected and reviewed 707 of 2840 available handoff records generated on the medicine service of an academic medical center between August 1, 2012 and December 31, 2012. We used both quantitative and qualitative analytical techniques to characterize sign-outs in the following dimensions: completeness, usefulness and accuracy of information content, handoff task category, logic, internal consistency and appropriateness of assigned tasks, and composition and complexity of assigned tasks. The degree of completeness of information varied considerably across domains. Completeness was highest for entry of assigned tasks (99.9%), nearly as high for hospital course/presenting illness (95%), and relatively high (87%-98%) for entry of provider name and contact information, principal diagnosis, allergies, current clinical condition, mental status, and code status. Eighty-eight percent written handoffs described clinical condition and hospital course and whether there were tasks to complete. In 58% of suitable records, all problems listed in the electronic health record (EHR) were also present in the history of present illness. The accuracy of entered information also displayed wide variation. Only 80% of cardiovascular medications matched the contemporaneous EHR pharmacy record. Birth dates and allergies were identical in the handoff system and EHR in 95% and 86% of respective records. Of assigned tasks, 8% contained at least 1 unnecessary component or illogical/internally inconsistent element. Use of a handoff system, which organizes information entry through a standard template, promotes completeness of written handoff information. Inaccuracies in handoff data are associated with manual entry and should be discouraged. Programs should be encouraged to develop robust interfaces between the EHR and handoff platforms to promote entry of complete and accurate data and to enhance provider workflow.

The Secretome of Hydrogel-Coembedded Endothelial Progenitor Cells and Mesenchymal Stem Cells Instructs Macrophage Polarization in Endotoxemia.

UNLABELLED: : We previously reported the delivery of endothelial progenitor cells (EPCs) embedded in hyaluronic acid-based (HA)-hydrogels protects renal function during acute kidney injury (AKI) and promotes angiogenesis. We attempted to further ameliorate renal dysfunction by coembedding EPCs with renal mesenchymal stem cells (MSCs), while examining their paracrine influence on cytokine/chemokine release and proinflammatory macrophages. A live/dead assay determined whether EPC-MSC coculturing improved viability during lipopolysaccharide (LPS) treatment, and HA-hydrogel-embedded delivery of cells to LPS-induced AKI mice was assessed for effects on mean arterial pressure (MAP), renal blood flow (RBF), circulating cytokines/chemokines, serum creatinine, proteinuria, and angiogenesis (femoral ligation). Cytokine/chemokine release from embedded stem cells was examined, including effects on macrophage polarization and release of proinflammatory molecules. EPC-MSC coculturing improved stem cell viability during LPS exposure, an effect augmented by MSC hypoxic preconditioning. The delivery of coembedded EPCs with hypoxic preconditioned MSCs to AKI mice demonstrated additive improvement (compared with EPC delivery alone) in medullary RBF and proteinuria, with comparable effects on serum creatinine, MAP, and angiogenesis. Exposure of proinflammatory M1 macrophages to EPC-MSC conditioned medium changed their polarization to anti-inflammatory M2. Incubation of coembedded EPCs-MSCs with macrophages altered their release of cytokines/chemokines, including enhanced release of anti-inflammatory interleukin (IL)-4 and IL-10. EPC-MSC delivery to endotoxemic mice elevated the levels of circulating M2 macrophages and reduced the circulating cytokines/chemokines. In conclusion, coembedding EPCs-MSCs improved their resistance to stress, impelled macrophage polarization from M1 to M2 while altering their cytokine/chemokines release, reduced circulating cytokines/chemokines, and improved renal and vascular function when MSCs were hypoxically preconditioned. SIGNIFICANCE: This report provides insight into a new therapeutic approach for treatment of sepsis and provides a new and improved strategy using hydrogels for the delivery of stem cells to treat sepsis and, potentially, other injuries and/or diseases. The delivery of two different stem cell lines (endothelial progenitor cells and mesenchymal stem cells; delivered alone and together) embedded in a protective bioengineered scaffolding (hydrogel) offers many therapeutic benefits for the treatment of sepsis. This study shows how hydrogel-delivered stem cells elicit their effects and how hydrogel embedding enhances the therapeutic efficacy of delivered stem cells. Hydrogel-delivered stem cells influence the components of the overactive immune system during sepsis and work to counterbalance the release of many proinflammatory and prodamage substances from immune cells, thereby improving the associated vascular and kidney damage.

Dual stent migration to the heart and pulmonary artery.

The practice of intravascular stenting largely grew out of the concept of stenting the coronaries in acute myocardial infarction. According to the recent United States Renal Data System data registry, there has been a significant increase in endovascular intervention (1.8-fold increase-from 52,380 to 98,148) with a 2.2-fold increase in stent deployment in hemodialysis access (3792-8514). With the increasing use of endovascular stents in the management of dialysis access stenosis, the incidence of stent-related complications has increased significantly. Stent-related complications include stent restenosis, thrombosis (narrowing of the vessel lumen and being a nidus for thombus formation), stent shortening, stent fracture, stent infection, and stent migration. Physiologic variation in the diameter of veins due to respiration, which along with the geometry of the stent, can lead to a shortening lengthening of the stent-resulting in poor wall contact or high-speed impact of shock; in the case of trauma, mechanical bucking can result in tortuous blood vessels thereby resulting in stent migration (however proving this association was not the aim of this article). We report a case of a 44-year-old female with end-stage renal disease on hemodialysis, with stent placement to treat a compromised arteriovenous graft. There have been many cases of stent migration in the past; however, this is the first case of dual stent migration to the heart and pulmonary artery from an unusual (lower extremity) arteriovenous graft location.