Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.

BACKGROUND: Tocilizumab, a monoclonal antibody directed against the interleukin-6 receptor, has been proposed to mitigate the cytokine storm syndrome associated with severe COVID-19. We aimed to investigate the association between tocilizumab exposure and hospital-related mortality among patients requiring intensive care unit (ICU) support for COVID-19. METHODS: We did a retrospective observational cohort study at 13 hospitals within the Hackensack Meridian Health network (NJ, USA). We included patients (aged ≥18 years) with laboratory-confirmed COVID-19 who needed support in the ICU. We obtained data from a prospective observational database and compared outcomes in patients who received tocilizumab with those who did not. We applied a multivariable Cox model with propensity score matching to reduce confounding effects. The primary endpoint was hospital-related mortality. The prospective observational database is registered on ClinicalTrials.gov, NCT04347993. FINDINGS: Between March 1 and April 22, 2020, 764 patients with COVID-19 required support in the ICU, of whom 210 (27%) received tocilizumab. Factors associated with receiving tocilizumab were patients' age, gender, renal function, and treatment location. 630 patients were included in the propensity score-matched population, of whom 210 received tocilizumab and 420 did not receive tocilizumab. 358 (57%) of 630 patients died, 102 (49%) who received tocilizumab and 256 (61%) who did not receive tocilizumab. Overall median survival from time of admission was not reached (95% CI 23 days-not reached) among patients receiving tocilizumab and was 19 days (16-26) for those who did not receive tocilizumab (hazard ratio [HR] 0·71, 95% CI 0·56-0·89; p=0·0027). In the primary multivariable Cox regression analysis with propensity matching, an association was noted between receiving tocilizumab and decreased hospital-related mortality (HR 0·64, 95% CI 0·47-0·87; p=0·0040). Similar associations with tocilizumab were noted among subgroups requiring mechanical ventilatory support and with baseline C-reactive protein of 15 mg/dL or higher. INTERPRETATION: In this observational study, patients with COVID-19 requiring ICU support who received tocilizumab had reduced mortality. Results of ongoing randomised controlled trials are awaited. FUNDING: None.

TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD? / TpTe e TpTe/QT: novos marcadores para prever morte súbita cardíaca na DRT?

ABSTRACT Introduction: Reliable markers to predict sudden cardiac death (SCD) in patients with end stage renal disease (ESRD) remain elusive, but echocardiogram (ECG) parameters may help stratify patients. Given their roles as markers for myocardial dispersion especially in high risk populations such as those with Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and TpTe/QT are independent risk factors for SCD in ESRD. Methods: Retrospective chart review was conducted on a cohort of patients with ESRD starting hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical centers for health care. Average age of all participants was 66 years and the majority were males, consistent with a US veteran population. ECGs that were performed within 18 months of dialysis initiation were manually evaluated for TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and these were assessed up to 5 years following dialysis initiation. Results: After exclusion criteria, 205 patients were identified, of whom 94 had a prolonged TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs. normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%, p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD: prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7% vs. normal 66.7%, p=0.39). Conclusions: In ESRD patients on hemodialysis, prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD or all-cause mortality.

RESUMO Introdução: Marcadores confiáveis para predizer morte súbita cardíaca (MSC) em pacientes com doença renal terminal (DRT) permanecem elusivos, mas os parâmetros do ecocardiograma (ECG) podem ajudar a estratificar os pacientes. Devido a seus papéis como marcadores para a dispersão miocárdica, especialmente em populações de alto risco, como aquelas com síndrome de Brugada, nós hipotetizamos que o intervalo pico da onda T ao final da onda T (TpTe) e TpTe/QT são fatores de risco independentes para MSC na DRT. Métodos: Revisão retrospectiva do prontuário foi realizada em uma coorte de pacientes com DRT iniciando a hemodiálise. Os pacientes eram veteranos de guerra americanos que utilizavam os centros médicos do Veterans Affairs para atendimento médico. A idade média de todos os participantes foi de 66 anos e a maioria era do sexo masculino, consistente com uma população veterana dos EUA. ECGs que foram realizados dentro de 18 meses após o início da diálise, e foram avaliados manualmente para TpTe e TpTe/QT. Os desfechos primários foram MSC e mortalidade por todas as causas, e estes foram avaliados até 5 anos após o início da diálise. Resultados: Após o critério de exclusão, foram identificados 205 pacientes, dos quais 94 com TpTe prolongado e 61 com intervalo TpTe/QT prolongado (não mutuamente exclusivo). A mortalidade geral foi de 70,2% em 5 anos e a MSC foi de 15,2%. Nenhuma diferença significativa foi observada nos desfechos primários ao se avaliar o TpTe (MSC: prolongado 16,0% versus normal 14,4%, p = 0,73; mortalidade por todas as causas: prolongado 55,3% vs. normal 47,7%, p = 0,43). Da mesma forma, nenhuma diferença significativa foi encontrada para TpTe/QT (MSC: prolongado 15,4% vs. normal 15,0%, p = 0,51; mortalidade por todas as causas: prolongado 80,7% vs. normal 66,7%, p = 0,39). Conclusões: Em pacientes com insuficiência renal terminal em hemodiálise, TpTe ou TpTe/QT prolongados não foram associados a um aumento significativo da morte súbita ou mortalidade por todas as causas.

TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD?

INTRODUCTION: Reliable markers to predict sudden cardiac death (SCD) in patients with end stage renal disease (ESRD) remain elusive, but electrocardiogram (ECG) parameters may help stratify patients. Given their roles as markers for myocardial dispersion especially in high risk populations such as those with Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and TpTe/QT are independent risk factors for SCD in ESRD. METHODS: Retrospective chart review was conducted on a cohort of patients with ESRD starting hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical centers for health care. Average age of all participants was 66 years and the majority were males, consistent with a US veteran population. ECGs that were performed within 18 months of dialysis initiation were manually evaluated for TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and these were assessed up to 5 years following dialysis initiation. RESULTS: After exclusion criteria, 205 patients were identified, of whom 94 had a prolonged TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs. normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%, p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD: prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7% vs. normal 66.7%, p=0.39). CONCLUSIONS: In ESRD patients on hemodialysis, prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD or all-cause mortality.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis.

Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology.

Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma.

Atypical hemolytic uremic syndrome: Laboratory characteristics, complement-amplifying conditions, renal biopsy, and genetic mutations.

Atypical hemolytic uremic syndrome (aHUS) is characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and widespread damage to multiple organs including the kidney. The syndrome has a high mortality necessitating the need for an early diagnosis to limit target organ damage. Because thrombotic microangiopathies present with similar clinical picture, accurate diagnosis of aHUS continues to pose a diagnostic challenge. This article focuses on the role of four distinct aspects of aHUS that assist clinicians in making an accurate diagnosis of aHUS. First, because of the lack of a single specific laboratory test for aHUS, other forms of thrombotic microangiopathies such as thrombotic thrombocytopenic purpura and Shiga toxin-associated HUS must be excluded to successfully establish the diagnosis of aHUS. Second, application of the knowledge of complement-amplifying conditions is critically important in making an accurate diagnosis. Third, when available, a renal biopsy can reveal changes consistent with thrombotic microangiopathy. Fourth, genetic mutations are increasingly clarifying the underlying complement dysfunction and gaining importance in the diagnosis and management of patients with aHUS. This review concentrates on the four aspects of aHUS and calls for heightened awareness in making an accurate diagnosis of aHUS.

Prevalence of chronic kidney disease among patients undergoing transradial percutaneous coronary interventions.

BACKGROUND: While transradial approach to conduct percutaneous coronary interventions offers multiple advantages, the procedure can cause radial artery damage and occlusion. Because radial artery is the preferred site for the creation of an arteriovenous fistula to provide dialysis, patients with chronic kidney disease are particularly dependent on radial artery for their long-term survival. METHODS: In this retrospective study, we investigated the prevalence of chronic kidney disease in patients undergoing coronary interventions via radial artery. Stage of chronic kidney disease was based on estimated glomerular filtration rate and National Kidney Foundation - Kidney Disease Outcomes Quality Initiative guidelines. RESULTS: A total of 497 patients undergoing transradial percutaneous coronary interventions were included. Over 70.4% (350/497) of the patients had chronic kidney disease. Stage II chronic kidney disease was observed in 243 (69%) patients (estimated glomerular filtration rate = 76.0 ± 8.4 mL/min). Stage III was observed in 93 (27%) patients (estimated glomerular filtration rate = 49 ± 7.5 mL/min). Stage IV chronic kidney disease was observed in 5 (1%) patients (estimated glomerular filtration rate = 25.6 ± 4.3 mL/min) and Stage V chronic kidney disease was observed in 9 (3%) patients (estimated glomerular filtration rate = 9.3 ± 3.5 mL/min). Overall, 107 of 350 patients (30%) had advanced chronic kidney disease, that is, stage III-V chronic kidney disease. Importantly, 14 of the 107 (13%) patients had either stage IV or V chronic kidney disease. CONCLUSION: This study finds that nearly one-third of the patients undergoing transradial percutaneous coronary interventions have advanced chronic kidney disease. Because many of these patients may require dialysis, the use of radial artery to conduct percutaneous coronary interventions must be carefully considered in chronic kidney disease population.

Pregnancy and hemodialysis access: A case for patient satisfaction in favor of a tunneled dialysis catheter.

While an arteriovenous fistula is the best available access, many patients continue to rely on a tunneled hemodialysis catheter for dialysis therapy. Despite the highest risk of catheter-related bacteremia and associated morbidity and mortality, patients often prefer tunneled hemodialysis catheter to avoid pain associated with cannulation of an arteriovenous access. We report three tunneled hemodialysis catheter-dependent end-stage renal disease patients (age: 38, 35, 33 years), who became pregnant. Pregnancy was discovered at 10, 12 and 10 weeks of gestation. All three patients were switched to daily hemodialysis (six sessions/week) as soon as the pregnancy was discovered. The three patients had refused the placement of an arteriovenous access and expressed their strong preference for tunneled hemodialysis catheter. All had been educated about the risks and benefits of catheter, grafts, and fistulas. Patient preference was acknowledged and dialysis therapy was continued with tunneled hemodialysis catheter. Pregnancy was uneventful in two patients with the delivery of a healthy baby. The third patient had a miscarriage. Patient preference for tunneled hemodialysis catheter and satisfaction is important and can result in a successful outcome in pregnant patients. Nonetheless, in keeping with the National Kidney Foundation guidelines as well as the Fistula First, an arteriovenous fistula should be offered to hemodialysis patients. At the same time, patient's preference and wish should be respected and followed.

Complement activation in atypical hemolytic uremic syndrome and scleroderma renal crisis: a critical analysis of pathophysiology / Ativação de complemento em síndrome urêmica hemolítica atípica e crise renal por esclerodermia: uma análise crítica da fisiopatologia

ABSTRACT Scleroderma is an autoimmune disease that affects multiple systems. While pathophysiologic mechanisms governing the development of scleroderma are relatively poorly understood, advances in our understanding of the complement system are clarifying the role of complement pathways in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis. The abundant similarities in their presentation as well as the clinical course are raising the possibility of a common underlying pathogenesis. Recent reports are emphasizing that complement pathways appear to be the unifying link. This article reviews the role of complement system in the development of atypical hemolytic uremic syndrome and scleroderma renal crisis, and calls for heightened awareness to the development of thrombotic angiopathy in patients with scleroderma.

RESUMO A esclerodermia é uma doença autoimune que afeta múltiplos sistemas. Embora os mecanismos fisiopatológicos que regem o desenvolvimento da esclerodermia sejam relativamente pouco compreendidos, os avanços em nossa compreensão do sistema do complemento estão esclarecendo o papel das vias do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal da esclerodermia. As abundantes semelhanças em sua apresentação, bem como o curso clínico, estão aumentando a possibilidade de uma patogênese subjacente comum. Relatórios recentes estão enfatizando que as vias de complemento parecem ser o link unificador. Este artigo analisa o papel do sistema do complemento no desenvolvimento da síndrome urêmica hemolítica atípica e da crise renal na esclerodermia, e exige maior conscientização para com o desenvolvimento da angiopatia trombótica em pacientes com esclerodermia.

The Complications of Vascular Access in Hemodialysis.

Complications related to hemodialysis vascular access continue to have a major impact on morbidity and mortality. Vascular access dysfunction is the single most important factor that determines the quality of dialysis treatment. Vascular access stenosis is a common complication that develops in a great majority of patients with an arteriovenous access and leads to access dysfunction. By restricting luminal diameter, this complication leads to a reduction in blood flow and places the access at risk for thrombosis. Similarly, the development of catheter-related fibroepithelial sheath also causes catheter dysfunction with its detrimental effects on blood flow. In this article, we discuss the most common complications associated with dialysis access and provide therapeutic options to manage these problems.

Subcutaneous defibrillators for dialysis patients.

Defibrillation can be successfully provided by the subcutaneous implantable cardioverter defibrillator (ICD) without the leads. In contrast, traditional ICDs require leads that can cause central venous stenosis, lead-induced endocarditis, and carry the risk of tricuspid regurgitation by valve adhesion, perforation, coaptation interference, or entanglement. Central venous stenosis, infection, and tricuspid regurgitation are all critically important considerations in hemodialysis patients. Recent reports are supporting the use of subcutaneous ICDs in renal patients maintained on long-term hemodialysis. This article provides the risks associated with leads of traditional defibrillators and raises awareness of the subcutaneous ICD and their benefits for hemodialysis patients.

Management of hypertension in patients during percutaneous dialysis access interventions.

Not infrequently, interventionalists are faced with a patient with increased blood pressure who is about to undergo a dialysis access intervention such as tunneled hemodialysis catheter, percutaneous balloon angioplasty, or declotting procedure for a clotted arteriovenous access. This can frequently create a dilemma as functional dialysis access is needed to provide dialysis therapy and delaying treatment could result in a life-threatening situation, particularly in the presence of hyperkalemia. This article investigates hypertension in patients undergoing percutaneous dialysis access interventions and provides guidance to their management.

Ischemic monomelic neuropathy: a long-term follow-up of two cases.

INTRODUCTION: Ischemic monomelic neuropathy (IMN) is the most dreaded complication of an arteriovenous access creation. While uncommon, it can lead to pain, paresthesia or/and hand weakness. Creation of an arteriovenous connection causing a sudden diversion of blood away from the nerves can lead to ischemic injury to the neural tissue and cause IMN. Immediate surgical ligation has been traditionally recommended to limit ongoing neural tissue injury. CASE DESCRIPTION: We present two diabetic patients who developed IMN after the creation of a left upper extremity brachial-cephalic fistula and refused to undergo surgical ligation. The clinical examination revealed paresthesia localized to the volar aspect of the left forearm with mild weakness of the thumb, index and middle finger. Rehabilitation therapy was initiated in both and revealed a significant improvement in weakness but paresthesia persisted. Fistula maturation was achieved in both patients with an access flow of 1100-1200 cc/min. At 4 months, fistula was used successfully for dialysis in both patients. At a follow-up of 11 months, hand weakness did not progress and paresthesia disappeared. CONCLUSIONS: These cases demonstrate sensory-motor improvement with time and rehabilitation therapy and challenge the traditional approach of fistula ligation. The approach presented in this paper also results in the preservation of the lifeline of a patient. Future investigations should focus on identifying candidates who could benefit from physical therapy and rehabilitation.

Surgical biopsy: its appropriateness in diagnosing interstitial lung disease.

PURPOSE OF REVIEW: Our goal is to update advances in the use of surgical lung biopsy in the idiopathic interstitial pneumonias. We discuss an approach for identifying patients with idiopathic interstitial pneumonias who may benefit from surgical lung biopsy, newer surgical approaches and complications and risks of surgery. RECENT FINDINGS: A consensus statement on idiopathic interstitial pneumonias has described the natural history and response to therapy of idiopathic interstitial pneumonias. The statement discussed selection of patients with idiopathic interstitial pneumonias for surgical lung biopsy and avoidance of unneeded biopsy, particularly for patients with 'classical' radiographic findings of idiopathic pulmonary fibrosis. Video-assisted thoracoscopic lung biopsy continues to be the standard procedure for surgical lung biopsy. Newer approaches have used outpatient surgery for selected patients, earlier removal of chest tubes and modifications of surgical technique. At-risk patients include those with respiratory failure, rapid progression of disease, pulmonary hypertension and advanced disease. SUMMARY: Standard video-assisted thoracoscopic lung biopsy should be considered in patients with interstitial lung diseases of unknown cause who have a subacute course, ground-glass opacities on high-resolution computed tomography or features atypical for idiopathic pulmonary fibrosis, as these patients may respond to therapy. A step-wise process for selection of patients for surgical lung biopsy is recommended.