Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer

Objective: Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. Methods: Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80 MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. Results: Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. Conclusion: Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accuratel

Hepatitis-B- und -C-assoziierte Glomerulonephritiden

Zusammenfassung: Virale Hepatitiden sind häufig mit extrahepatischen Manifestationen assoziiert. Bei der HepatitisB ist die membranöse Glomerulonephritis (GN) die häufigste histologische Diagnose. Im Rahmen der HepatitisC wird vorwiegend eine membranoproliferative GN mit oder ohne gemischte Kryoglobulinämie beobachtet. Eine zentrale pathogenetische Rolle spielen Immunkomplexe (virale Antigene, antivirale Antikörper, bei Kryoglobulinämie auch Rheumafaktoren). Diese Komplexe werden in der Niere abgelagert und aktivieren Komplement, was schließlich zum Nierenschaden führt. Therapeutisch zentral ist die antivirale Therapie mit dem Ziel der Antigenelimination. Im Falle der HepatitisB kann eine Therapie mit IFNα durchgeführt werden, alternativ mit Lamivudin. Eine immunsuppressive Therapie steht eher im Hintergrund. Bei der HepatitisC ist die Standardtherapie IFNα in Kombination mit Ribavirin. Bei einer zusätzlichen Kryoglobulinämie besteht die Alternative einer Therapie mit Rituximab, bei schwerem Verlauf mit Plasmapherese, Steroiden und Cyclophosphamid. Bei vollständiger Elimination der Virusreplikation ist die Prognose dieser sekundären GN günsti

Anti-hLAMP2-antibodies and dual positivity for anti-GBM and MPO-ANCA in a patient with relapsing pulmonary-renal syndrome

Background Pulmonary-renal syndrome associated with anti-glomerular basement membrane (GBM) antibodies, also known as Goodpasture's syndrome, is a rare but acute and life-threatening condition. One third of patients presenting as anti-GBM antibody positive pulmonary-renal syndrome or rapidly progressive glomerulonephritis are also tested positive for anti-neutrophil cytoplasmic antibodies (ANCA). Whilst anti-GBM disease is considered a non-relapsing condition, the long-term course of double-positive patients is less predictable. Case Presentation We report a patient with such dual positivity, who presented with pulmonary hemorrhage, crescentic glomerulonephritis and membranous nephropathy. Plasmapheresis in combination with immunosuppresive therapy led to a rapid remission but the disease relapsed after two years. The serum of the patient was tested positive for antibodies to human lysosomal membrane protein 2 (hLAMP2), a novel autoantigen in patients with active small-vessel vasculitis (SVV). The anti-hLAMP2 antibody levels correlated positively with clinical disease activity in this patient. Conclusion We hypothesize that this antibody may indicate a clinical course similar to ANCA-associated vasculitis in double-positive patients. However, this needs to be confirmed on comprehensive patient cohorts

Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Implications of early respiratory support strategies on disease progression in critical COVID-19 : a matched subanalysis of the prospective RISC-19-ICU cohort

Background: Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Methods: Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Results: Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). Conclusion: In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

FAT1 mutations cause a glomerulotubular nephropathy

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal disease entity in four families with a combination of SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss of FAT1 results in decreased cell adhesion and migration in fibroblasts and podocytes and the decreased migration is partially reversed by a RAC1/CDC42 activator. Podocyte-specific deletion of Fat1 in mice induces abnormal glomerular filtration barrier development, leading to podocyte foot process effacement. Knockdown of Fat1 in renal tubular cells reduces migration, decreases active RAC1 and CDC42, and induces defects in lumen formation. Knockdown of fat1 in zebrafish causes pronephric cysts, which is partially rescued by RAC1/CDC42 activators, confirming a role of the two small GTPases in the pathogenesis. These findings provide new insights into the pathogenesis of SRNS and tubulopathy, linking FAT1 and RAC1/CDC42 to podocyte and tubular cell function.</p

Akute/subakute Niereninsuffizienz: Leitsymptome: Akuter Anstieg des Serumkreatinins und/oder Oligurie/Anurie

Eine Niereninsuffizienz kann akut auftreten, sich aber auch über Wochen und Monate entwickeln. Die Unterscheidung in eine akute, subakute oder chronische Form ist nicht immer eindeutig.Mischformen wie z.B. eine akute Exazerbation einer chronischen Niereninsuffizienz sind nicht selten. Wichtig ist es, eine akute Niereninsuffizienz zu erkennen und zu wissen, welche diagnostischen Massnahmen ergriffen werden müssen. Dazu wird ein Algorithmus vorgeschlagen. Eine akut auftretendeNiereninsuffizienz kann von Symptomen wie Flankenschmerzen oder einem Hautausschlag begleitet sein, die auf die Ursache hinweisen, oder von Symptomen wie Ödeme und Hypertonie, die eine Folge der Niereninsuffizienz sind. Bei einem subakuten Verlauf können Symptome auch völlig fehlen, und die Diagnose wird zufällig gestellt

Massive uric acid nephrolithiasis with progressive renal failure due to spontaneous tumour lysis syndrome

Tumour lysis syndrome (TLS) is a constellation of metabolic complications due to the rapid destruction of malignant cells, causing renal, cardiac or cerebral dysfunction. Electrolyte abnormalities include hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. TLSinduced renal failure is mainly caused by uric acid and calcium phosphate crystal deposition and usually develops following cytotoxic chemotherapy. Here, we present a case of spontaneous TLS in a patient with chronic myelomonocytic leukaemia (CMML) with massive uric acid stone and crystal formation and rapidly worsening renal failure. Autopsy revealed underlying tumourous kidney infiltration. Risk factors for occurrence of TLS and current therapeutic management are discussed