Case report of simultaneous presentation of pulmonary embolism and pericardial effusion following an oncological esophagectomy

INTRODUCTION: This is the first reported case of simultaneous presentation of pulmonary embolism and pericardial effusion following esophagectomy. This case illustrates a diagnostic and therapeutic challenge exemplifying the difficulties arising from complex anticoagulant considerations in esophageal cancer. PATIENT CASE: A 72 year old male undergoes an oncological esophageal resection. Postoperatively the patient develops pulmonary embolism for which he is treated with Rivaroxaban. After starting Rivaroxaban the patient develops a large pericardial effusion. DISCUSSION: We suspect that the treatment of pulmonary embolism with Rivaroxaban had a causative role in the development of pericardial effusion. Based on literature we suspect that chemoradiotherapy increased susceptibility. CONCLUSION: Diagnosis and treatment of simultaneous pulmonary embolism and pericardial effusion remains a challenge. Special consideration should be taken when using Rivaroxaban in esophageal cancer patients; this should always be conducted in consultation with a coagulation specialist. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Acute and chronic histopathological findings in renal biopsies in COVID-19

The dominant ICU admission diagnosis of COVID-19 patients is respiratory insufficiency, but 32–57% of hospitalized COVID-19 patients develop acute kidney injury (COVID-AKI). The renal histopathological changes accompanying COVID-AKI are not yet fully described. To obtain a detailed insight into renal histopathological features of COVID-19, we conducted a review including all studies reporting histopathological findings of diagnostic and postmortem kidney biopsies from patients with COVID-19 published between January 1, 2020, and January 31, 2021. A total of 89 diagnostic and 194 postmortem renal biopsies from individual patients in 39 published studies were investigated and were included in the analysis. In the diagnostic biopsy group, mean age was 56 years and AKI incidence was 96%. In the postmortem biopsy group, mean age was 69 years and AKI incidence was 80%. In the diagnostic biopsy group, the prevalence of acute glomerular diseases was 74%. The most common glomerular lesions were collapsing focal segmental glomerulosclerosis (c-FSGS) in 54% and thrombotic microangiopathy (TMA) in 9% of patients. TMA was also found in 10% of patients in the postmortem biopsy group. The most common acute tubular lesions was acute tubular necrosis (ATN) which was present in 87% of patients in the diagnostic and in 77% of patients in the postmortem biopsy group. Additionally, we observed a high prevalence of preexisting chronic lesions in both groups such as atherosclerosis and glomerulosclerosis. Histopathological changes in renal biopsies of COVID-19 patients show a heterogeneous picture with acute glomerular lesions, predominantly c-FSGS and TMA, and acute tubular lesions, predominantly ATN. In many patients, these lesions were present on a background of chronic renal injury. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10238-022-00941-x

Comparison of renal histopathology and gene expression profiles between severe COVID-19 and bacterial sepsis in critically ill patients

BACKGROUND: The mechanisms driving acute kidney injury (AKI) in critically ill COVID-19 patients are unclear. We collected kidney biopsies from COVID-19 AKI patients within 30 min after death in order to examine the histopathology and perform mRNA expression analysis of genes associated with renal injury. METHODS: This study involved histopathology and mRNA analyses of postmortem kidney biopsies collected from patients with COVID-19 (n = 6) and bacterial sepsis (n = 27). Normal control renal tissue was obtained from patients undergoing total nephrectomy (n = 12). The mean length of ICU admission-to-biopsy was 30 days for COVID-19 and 3–4 days for bacterial sepsis patients. RESULTS: We did not detect SARS-CoV-2 RNA in kidney biopsies from COVID-19-AKI patients yet lung tissue from the same patients was PCR positive. Extensive acute tubular necrosis (ATN) and peritubular thrombi were distinct histopathology features of COVID-19-AKI compared to bacterial sepsis-AKI. ACE2 mRNA levels in both COVID-19 (fold change 0.42, p = 0.0002) and bacterial sepsis patients (fold change 0.24, p < 0.0001) were low compared to control. The mRNA levels of injury markers NGAL and KIM-1 were unaltered compared to control tissue but increased in sepsis-AKI patients. Markers for inflammation and endothelial activation were unaltered in COVID-19 suggesting a lack of renal inflammation. Renal mRNA levels of endothelial integrity markers CD31, PV-1 and VE-Cadherin did not differ from control individuals yet were increased in bacterial sepsis patients (CD31 fold change 2.3, p = 0.0006, PV-1 fold change 1.5, p = 0.008). Angiopoietin-1 mRNA levels were downregulated in renal tissue from both COVID-19 (fold change 0.27, p < 0.0001) and bacterial sepsis patients (fold change 0.67, p < 0.0001) compared to controls. Moreover, low Tie2 mRNA expression (fold change 0.33, p = 0.037) and a disturbed VEGFR2/VEGFR3 ratio (fold change 0.09, p < 0.0001) suggest decreased microvascular flow in COVID-19. CONCLUSIONS: In a small cohort of postmortem kidney biopsies from COVID-19 patients, we observed distinct histopathological and gene expression profiles between COVID-19-AKI and bacterial sepsis-AKI. COVID-19 was associated with more severe ATN and microvascular thrombosis coupled with decreased microvascular flow, yet minimal inflammation. Further studies are required to determine whether these observations are a result of true pathophysiological differences or related to the timing of biopsy after disease onset. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13054-021-03631-4

2 days versus 5 days of postoperative antibiotics for complex appendicitis:a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.</p

Renal Klotho is Reduced in Septic Patients and Pretreatment With Recombinant Klotho Attenuates Organ Injury in Lipopolysaccharide-Challenged Mice

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