Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment?

Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFα). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang-2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFα production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells.

Renal artery infarction in the SARS-Cov-2 era: A systematic review of case reports.

AIM: Renal artery infarction (RI) is the presence of blood clot in the main renal artery or its branches causing complete or partial obstruction of the blood supply. Its etiology is either related with disorders of the renal vasculature or with cardiovascular diseases. Recently, the SARSCoV- 2 virus is an emerging cause of thromboembolic events and the incidence of RI is anticipated to increase after the pandemic. METHODS: A systematic review based on COVID-19 associated RI was conducted. PROTOCOL: A systematic review of the Medline/Pubmed and Scopus databases was conducted in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (the PRISMA statement). Search strategy and information sources: A hand-search was performed using the terms "SARS-Cov-2" OR "COVID-19" AND "renal thrombosis" OR "renal infarction" OR "renal "thromboembolism". ELIGIBILITY CRITERIA: all types of publications (case reports, case series, letters to the editor, short communications) were evaluated for relevance. Inclusion criteria were: confirmed SARS-Cov-2 infection irrespectively of the age, diagnosis of RI during or after the onset of viral infection, and exclusion of other potential causes of thromboembolic event except of SARS-Cov-2. Patients with renal transplantation were also considered. Study criteria selection: after checking for relevance based on the title and the abstract, the full texts of the selected papers were retrieved and were further evaluated. Duplicated and irrelevant cases were excluded. Any disagreement was resolved by consensus with the involvement of a third reviewer. Quality of studies: The assessment of the quality case reports was based on four different domains: selection, ascertainment, casualty and reporting. Each paper was classified as "Good", "Moderate" and "Poor" for any of the four domains. Data extractions: Crucial data for the conduct of the study were extracted including: age, sex, time from SARS-Cov-2 infection till RI development, medical history, previous or current antithrombotic protection or treatment, laterality and degree of obstruction, other sites of thromboembolism, treatment for thromboembolism and SARS-Cov-2 and final outcome. DATA ANALYSIS: methods of descriptive statistics were implicated for analysis and presentation of the data. RESULTS: The systematic review retrieved 35 cases in 33 reports. In most cases, RI was diagnosed within a month from the SARSCov- 2 infection albeit 17 out of 35 patients were receiving or had recently received thromboprophylaxis. Right, left, bilateral and allograft obstruction was diagnosed in 7, 15, 8 and 5 patients respectively. 17 cases experienced additional extrarenal thromboembolism primarily in aorta, spleen, brain and lower limbs. Low molecular weight heparins (LMWH) (usually 60-80 mg enoxaparine bid) was the primary treatment, followed by combinations of unfractionated heparin and salicylic acid, apixaban and rivaraxaban, warfarin, acenocoumarol or clopidogrel. Kidney replacement therapy was offered to five patients while invasive therapies with thrombus aspiration or catheter directed thrombolysis were performed in two. Regarding the outcomes, five of the patients died. The total renal function was preserved in 17 cases and renal impairment with or without hemodialysis was recorded in 5 patients, two of them having lost their kidney allografts. LIMITATIONS: The majority of included studies are of moderate quality. The results and the conclusions are based on case-reports only and crucial data are dissimilarly presented or missing through the relevant publications. CONCLUSIONS: Thromboprophylaxis may not offer adequate protection against SARS-Cov-2 induced thrombosis. Most patients could be effectively treated with conservative measures, while in more severe cases aggressive treatment could be recommended. IMPLICATIONS OF KEY FINDINGS: Therapeutic doses of LMWH could be considered for protection against RI in SARS-Cov-2 cases. Interventional treatment could be offered in a minority of more severe cases after carful balancing the risks and benefits.

Granuloma of the appendiceal stump. An unusual cause of right hemicolectomy.

Granuloma of the appendiceal stump is not a common surgical entity. However, hemorrhage which may lead to right hemicolectomy is rare in fact. We report this case, in order to avoid this kind of overtherapy.

Combined side-to-end anastomosis with temporary end colostomy for the management of selected left-sided colonic emergencies.

Management of surgical emergencies of the left colon commonly requires excision of the colonic segment bearing the lesion, creation of an end colostomy, and closure of the rectosigmoid stump. Closure of the end stoma may be technically challenging. During this study, we used a new surgical technique involving the creation of an end-to-side anastomosis of the rectosigmoid stump to the base of the proximal colonic segment in association with an end colostomy. During a 15-year period, 23 patients were offered this type of surgery. Mortality was zero. Complications were observed in seven patients (morbidity, 7/23). Mean hospitalization time was 12.3 days. Closure of the colostomy was performed approximately 1 month after initial surgery and was easily performed using a mechanical stapler, either intraperitoneally or even extraperitoneally. No complications were observed after closure of the colostomy. The described technique is a useful alternative for the management of selected patients with left-sided colonic surgical emergencies. Its main advantage is that it greatly facilitates colostomy closure, which is performed earlier compared with the colostomy closure after a typical Hartmann's procedure.

Medullary thyroid carcinoma: The third most common thyroid cancer reviewed.

Medullary thyroid cancer is a type of thyroid cancer of neuroendocrine origin. It occurs in hereditary and sporadic forms, and its aggressive behavior is associated with the clinical presentation and type of RET mutation. Total thyroidectomy remains the ideal choice of treatment. Early diagnosis and treatment are the fundamental for a 100% cure rate. In this study, we present our experience of 3 cases, along with a complete review of the literature derived from a Pubmed Database search.