Case Report: Medullary Thyroid Cancer Workup Initiated by Unexpectedly High Procalcitonin Level-Endocrine Training Saves Life in the COVID-19 Unit.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic. The majority of medullary thyroid cancers present as a thyroid nodule. At the time of diagnosis, cervical lymph nodes and distant metastases are frequently detected. Case Report: Here, we present a case of a 46-year-old man with coronavirus disease (COVID) pneumonia, who had persistently high serum procalcitonin levels despite normal C-reactive protein levels. The attending infectologist happened to be a colleague who spent some time, as part of her internal medicine rotation, in the Endocrine Ward and recalled that medullary thyroid cancer might be the cause. This led to the timely workup and treatment of the medullary cancer.

Reconsidering the technical aspects and quality management background of faecal microbiota transplantation due to the novel coronavirus pandemic / A székletmikrobiota-transzplantáció technológiájának és minoségirányítási hátterének újragondolása a SARS-CoV-2 víruspandémia kapcsán.

Összefoglaló. A székletmikrobiota-transzplantáció (faecalismikrobiota-transzplantáció - FMT) a Clostridioides difficile fertozés (CDI) kezelésében nemzetközileg széles körben elfogadott, megfelelo szakmai háttér mellett végezve biztonságos, potenciálisan életmento, költséghatékony, valamint a hospitalizációs ido és az orvos-beteg találkozások jelentos redukálására képes eljárás. Az FMT elvégzésére egyes országokban magas szintu minoségirányítási háttérrel muködo, célfeladatra szervezodött donor- és székletbankok rendezkedtek be. Máshol, így például hazánkban, az eljáráshoz az egyértelmu jogi szabályozási környezet, a standardizált technológiai háttér és a finanszírozás hiánya miatt nem egységes a hozzáférés. Régóta idoszeru továbbá, hogy a heterogén, nemegyszer háztartási eszközökkel elokészített beavatkozások helyett a nemzetközi és legújabban már a hazai ajánlásokban is megfogalmazott, a betegbiztonságot legjobban garantáló elvárások mellett történjen a széklettranszplantáció. Az új koronavírus (SARS-CoV-2) okozta pandémia megjelenése eroteljes szakmai érv országos szinten az FMT minoségirányítási környezetének és technológiai hátterének újragondolására, mert a SARS-CoV-2 egyszerre jelent kockázatot a CDI miatt kórházban kezelt sérülékeny betegpopulációnak, és egyben veszélyezteti az FMT biztonságosságát mind a recipiens, mind pedig az eljárást végzo egészségügyi személyzet tekintetében. Ezekre a szakmai és társadalmi kihívásokra reagálva, a széles köru beteghozzáférés és a legmagasabb szintu betegbiztonság garantálására, a Debreceni Egyetemen új eljárásrendet dolgoztunk ki az FMT végzésére. Ezen eljárásrendnek a COVID-19-pandémia miatt módosított, a fagyasztottgraftbank üzemeltetése és a rendszerszemlélet tekintetében releváns elemeit ismertetjük. Javasolt, hogy országos szinten hasonló, megfelelo minoségirányítási és technológiai környezettel, a SARS-CoV-2-fertozés kizárását is integráló donorszurési rendszerrel, továbbá fagyasztottgraft-banki háttérrel muködo laboratóriumok vegyenek részt a széklettranszplantációk végzésében. Felmerül továbbá, hogy az eljárást a számos analógia és a donor-recipiens koncepció alapján a sejt- és szövettranszplantációkra vonatkozó szabályozórendszer keretei közé ajánlott beágyazni. Orv Hetil. 2020; 161(44): 1858-1871. Summary. Stool transplantation (faecal microbiota transplantation - FMT) is a widely accepted, potentially life-saving, cost-effective medical intervention for the treatment of Clostridioides difficile infection (CDI), which has an acceptable safety profile if performed with an appropriate professional background. FMT can significantly reduce hospitalization time and the number of patient visits. National donor and stool banks with high-standard quality management systems were established in certain countries for supporting the procedures. In other regions, including Hungary, patient access is not uniform due to the lack of clear legal regulations, standardized technology or financial reimbursement. It has been expected for a long time to replace the heterogenous techniques, occasionally utilizing household equipment with a technology providing improved patient safety and fulfilling international and recently published local FMT guidelines. The emergence of the novel coronavirus (SARS-CoV-2) pandemic is a very powerful argument in favour of urgently reconsidering the quality management and technological background of FMT procedures. SARS-CoV-2 is a major threat to the vulnerable patients suffering from CDI and also impose risks for the recipient and healthcare personnel involved in carrying out the transplantation. New FMT guidelines were implemented at the University of Debrecen to address these professional and public challenges, to provide wide patient access and to guarantee the highest achievable patient safety. Relevant elements of this new protocol are presented, focusing on a systemic quality management approach, on the operation of a frozen stool bank and on a modified donor screening algorithm taking the risks of COVID-19 into consideration. We suggest that laboratories with proper quality assurance and technological conditions, implementing SARS-CoV-2 donor screening and operating a frozen graft bank should participate in faecal microbiota transplantations. It is also recommended that, based on the analogies and the similar donor-recipient concept, FMT should be embedded under the organ tissue and cell transplantation polices in Hungary. Orv Hetil. 2020; 161(44): 1858-1871.

In vitro and in vivo Effect of Exogenous Farnesol Exposure Against Candida auris.

The spreading of multidrug-resistant Candida auris is considered as an emerging global health threat. The number of effective therapeutic regimens is strongly limited; therefore, development of novel strategies is needed. Farnesol is a quorum-sensing molecule with a potential antifungal and/or adjuvant effect; it may be a promising candidate in alternative treatment against Candida species including C. auris. To examine the effect of farnesol on C. auris, we performed experiments focusing on growth, biofilm production ability, production of enzymes related to oxidative stress, triazole susceptibility and virulence. Concentrations ranging from 100 to 300 µM farnesol caused a significant growth inhibition against C. auris planktonic cells for 24 h (p < 0.01-0.05). Farnesol treatment showed a concentration dependent inhibition in terms of biofilm forming ability of C. auris; however, it did not inhibit significantly the biofilm development at 24 h. Nevertheless, the metabolic activity of adhered farnesol pre-exposed cells (75 µM) was significantly diminished at 24 h depending on farnesol treatment during biofilm formation (p < 0.001-0.05). Moreover, 300 µM farnesol exerted a marked decrease in metabolic activity against one-day-old biofilms between 2 and 24 h (p < 0.001). Farnesol increased the production of reactive species remarkably, as revealed by 2',7'-dichlorofluorescein (DCF) assay {3.96 ± 0.89 [nmol DCF (OD640)-1] and 23.54 ± 4.51 [nmol DCF (OD640)-1] for untreated cells and farnesol exposed cells, respectively; p < 0.001}. This was in line with increased superoxide dismutase level {85.69 ± 5.42 [munit (mg protein)-1] and 170.11 ± 17.37 [munit (mg protein)-1] for untreated cells and farnesol exposed cells, respectively; p < 0.001}, but the catalase level remained statistically comparable between treated and untreated cells (p > 0.05). Concerning virulence-related enzymes, exposure to 75 µM farnesol did not influence phospholipase or aspartic proteinase activity (p > 0.05). The interaction between fluconazole, itraconazole, voriconazole, posaconazole, isavuconazole and farnesol showed clear synergism (FICI ranges from 0.038 to 0.375) against one-day-old biofilms. Regarding in vivo experiments, daily 75 µM farnesol treatment decreased the fungal burden in an immunocompromised murine model of disseminated candidiasis, especially in case of inocula pre-exposed to farnesol (p < 0.01). In summary, farnesol shows a promising therapeutic or adjuvant potential in traditional or alternative therapies such as catheter lock therapy.

Candida biofilm production is associated with higher mortality in patients with candidaemia.

BACKGROUND: Candidaemia is a common life-threatening disease among hospitalised patients, but the effect of the Candida biofilm-forming ability on the clinical outcome remains controversial. OBJECTIVE: The aim was to determine the impact of biofilms, specifically focusing on biofilm mass and metabolic activity, on the mortality in candidaemia. PATIENTS/METHODS: The clinical data of patients (n = 127) treated at the University of Debrecen, Clinical Centre, between January 2013 and December 2018, were investigated retrospectively. Biofilm formation was assessed using the crystal violet and XTT assays, measuring the biofilm mass and metabolic activity, respectively. Isolates were classified as low, intermediate and high biofilm producers both regarding biofilm mass and metabolic activity. The susceptibility of one-day-old biofilms to fluconazole, amphotericin B, anidulafungin, caspofungin and micafungin was evaluated and compared to planktonic susceptibility. RESULTS: Intermediate/high biofilm mass was associated with significantly higher mortality (61%). All Candida tropicalis, Candida parapsilosis and Candida glabrata isolates originating from fatal infections were intermediate/high biofilm producers, whereas this ratio was 85% for Candida albicans. Solid malignancy was associated with intermediate/high biofilm producers (P = .043). The mortality was significantly higher in infections caused by Candida strains producing biofilms with intermediate/high metabolic activity (62% vs. 33%, P = .010). The ratio of concomitant bacteraemia was higher for isolates forming biofilms with low metabolic activity (53% vs 28%, P = .015). CONCLUSIONS: This study provides evidence that the Candida biofilms especially with intermediate/high metabolic activity are related to higher mortality in candidaemia.

[Spontaneous bacterial peritonitis]. / Spontán bakteriális peritonitis.

Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

[Bacterial infection after orthotopic liver transplantation]. / Bakteriális infekciók májátültetés után.

INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.