COVID-19-associated pulmonary mycosis: a diagnostic dilemma

Introduction. Diabetes mellitus (DM) and corticosteroid treatment are independent risk factors for both: severe COVID-19 and lung mycosis. An uncontrolled DM and the use of corticosteroid in a background of COVID-19 appeared to increase the risk of mucormycosis in immunocompromised hosts. Because the diagnosis of fungal infections can be challenging, the empirical appropriate antifungal is critical to provide a successful outcome that was demonstrated in the presented case. Case presentation. A 40-year-old male, non-smoker, without any known chronic lung diseases, was referred to our clinic due to an episode of hemoptysis (30 ml). He was discharged from a hospital two weeks previously due to a severe form of COVID-19. A hyperglycemia was primarily diagnosed during the SARSCoV-2 infection, but no hypoglycemic treatment was initiated. High doses of corticosteroids were administered during the hospitalization for COVID-19 and a regimen of 12 mg/day of methylprednisolone has been started after discharge. At the admission to our hospital, he presented with hyperglycemia (22.8 mmol/l) and with HbA1C 9.4%. HRCT of the chest showed an area of consolidation in the right upper lobe close to the right hilum accompanied by lymphadenopathy. Bronchoscopy showed purulent, cheesy secretions, extensive necrosis of the right upper lobe segments. Histopathological examination of the lung and bronchial wall tissue obtained by transbronchial biopsy identified hyphae with invasion in the vessels and muscular tissue of the bronchial wall, highly suggestive for mucormycosis. Serological tests for Aspergillus fumigatus were negative. Antifungal treatment with itraconazole (the onliest available antifungal drug in the Republic of Moldova) was initiated, and no other episodes of hemoptysis and with an improvement of the bronchial and infectious clinical syndromes. HRCT of the thorax after two months of antifungal treatment demonstrated a resolution of the consolidation area and no lymph nodes enlargement. Discussion. Reports of COVID-19-associated mycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. In the absence of serum antigenic biomarkers and because the availability of PCR testing is low, particularly in low-income countries, COVID-19-associated mycosis diagnosis is challenging, with conventional culture and histopathological demonstration of fungi being the mainstay of diagnosis, albeit with low sensitivity. Conclusion. COVID-19-associated mucormycosis can be a serious complication of severe COVID-19, particularly in patients with uncontrolled diabetes. This case highlights the diagnostic and treatment challenges in a case of pulmonary mycosis associated with COVID-19

DESPRE STABILITATEA ÎN SENS LYAPUNOV A PUNCTELOR STAȚIONARE ÎN PROBLEMA MĂRGINITĂ A OPT CORPURI

Se consideră problema newtoniană mărginită a opt corpuri. Se studiază condițiile de existență a configurației prob­lemei și se determină soluțiile staționare (pozițiile de echilibru) în problema mărginită de opt corpuri cu simetrie in­completă. Se cercetează stabilitatea în sens Lyapunov a punctelor staționare stabile în prima aproximație.ABOUT LYAPUNOV  STABILITY OF STATIONARY POINTS IN THE RESTRICTED PROBLEM OF EIGHT BODIESThe Newtonian restricted problem of 8-bodies is considered. The conditions of existence of the con­fi­gu­ration are studied and the stationary solutions (equilibrium positions) in the restricted problem by eight bodies with in­com­plete symmetry is determined in this paper. We investigate Lyapunov stability of stable stationary points in the first approximation.</p

Tubular and cellular localization of the cardiac L-type calcium channel in rat kidney

Tubular and cellular localization of the cardiac L-type calcium channel in rat kidney.BackgroundThe mRNAs of several types of calcium channels have been identified in intact rat kidney, and L-type calcium channels cause changes in intracellular calcium in primary cultures of distal tubule cells. The aim of this study was to evaluate the tubular and cellular distribution of the α1C subunit of the L-type calcium channel in intact kidney.MethodsRT-PCR and Northern blot analysis were used to assess the regional abundance of the mRNA of this channel. Immunocytochemistry combined with confocal microscopy and surface biotinylation were applied to determine the tubular and cellular localization of the protein.ResultsNorthern blot and RT-PCR analysis indicated that the mRNA of the α1C subunit of the cardiac L-type calcium channel was present in whole rat kidney, kidney tubules and kidney cell lines. Western blot of lysates from whole kidney, kidney tubules or cell lines revealed bands of ∼190 kD for the α1C subunit and ∼60 kD for the β3 subunit. Confocal immunohistochemistry indicated that the α1C subunit of this channel was co-expressed in cells of the distal tubule that express calbindin-D28K, but not in intercalated cells. The α1C subunit was also highly expressed in both outer and inner medullary collecting ducts. Serial confocal microscopic images or surface biotinylation experiments determined that the channel was predominantly on the basolateral membrane but had some distribution on the apical membrane.ConclusionsThe distribution and cellular localization of the α1C subunit of cardiac L-type calcium channel suggest it is probably involved in intracellular and membrane calcium signaling

DETERMINAREA PUNCTELOR DE ECHILIBRU ÎN PROBLEMA MĂRGINITĂ A OPT CORPURI

Se consideră problema newtoniană mărginită a 8 corpuri. Se studiază condițiile de existență a configurației problemei și se determină soluțiile staționare (pozițiile de echilibru) în problema mărginită de opt corpuri cu simetrie incompletă. Calculele analitice și numerice sunt efectuate cu ajutorul sistemului Mathematica.DETERMINATION OF EQUILIBRIUM POINTS IN THE RESTRICTED PROBLEM OF EIGHT BODIESThe Newtonian restricted problem of 8-bodies is considered. The conditions of existence of the confi­guration are studied. The stationary solutions (equilibrium positions) in the restricted problem by eight bodies with incomplete symmetry is determined in this paper. Analytic and numerical calculations are done by with the system Mathematica.</p

COVID-19-ассоциированный легочный аспергиллез: от инвазивной к хронической форме.

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complicationaffecting critically ill patients with SARS-CoV-2 infection. Since the emerging number of cases and the high mortalityrate, there is an acute need for more information about the interaction between SARS‐CoV‐2 and Aspergillus spp., andthe treatment for CAPA.We present a case diagnosed with a severe form of CAPA, lung lesions being followed-up for 6 months.Aspergiloza pulmonară asociată COVID-19 (APAC) a fost raportată recent ca și o potențială complicație infecțioasă,care afectează pacienții critici cu infecție SARS-CoV-2. Având în vedere numărul mare de cazuri și rata ridicată a letalitățiiraportate în literatura de specialitate, este argumentată necesitatea mai multor date și studii referitoare la interacțiunea dintreSARS-CoV-2 și Aspergillus spp., precum și a celor de evaluare a schemelor terapeutice administrate și a eficacității acestora.Prezentăm cazul unui pacient diagnosticat cu o formă severă de APAC, fiind printre puținele cazuri publicate ale pacienților care au supraviețuit, cu o monitorizare a evoluției leziunilor pulmonare pentru o perioadă de 6 luni.COVID-19-ассоциированный инвазивный легочный аспергиллез (COVID-ИА) является потенциальным инфекционным осложнением, поражающим тяжелобольных пациентов с инфекцией SARS-CoV-2. В связи с растущим числом случаев и высоким уровнем смертности существует острая необходимость в дополнительнойинформации о взаимодействии между SARS ‐ CoV ‐ 2 и Aspergillus spp., а также о лечении COVID-ИА.Представляем случай с диагнозом тяжелой формы COVID-ИА, который подчеркивает проблему диагностикии лечения, с последующим 6-месячным мониторингом поражений легких

COVID-19 ассоциированный инвазивный аспергиллез легких

Infection with novel coronavirus (SARS-CoV-2) remains one of the most important pandemics till present, becoming an equation with several unknowns, one of them being the associated fungal infections. Pulmonary mycoses have an increased incidence and mortality, the most common germ identified among cases of COVID-19 is Aspergillus spp. Due to discrepancies in defining and diagnostic criteria, but also nonspecific clinical-imaging manifestations, COVID-19-associated pulmonary aspergillosis remains a diagnostic and management challengeInfecţia cu noul coronavirus SARS-CoV-2 rămâne una dintre cele mai importante pandemii până în prezent, devenind o ecuaţie cu mai multe necunoscute, una dintre necunoscute fiind şi infecţiile fungice asociate. Micozele pulmonare au o incidenţă şi mortalitate sporită, cel mai frecvent germene identificat printre cazurile de COVID-19 fiind Aspergillus spp. Datorită discordanţelor în definiţie şi în criteriile diagnostice, dar şi datorită caracterului nespecific al manifestărilor clinico-imagistice, aspergiloza pulmonară asociată COVID-19 rămâne o provocare în plan diagnostic şi de conduităВирус SARS-CoV-2 вызвал одну из самых тяжелых пандемий в истории человечества, многие аспекты которой на сегодняшний день остаются невыясненными, к примеру роль присоединения грибковой инфекции в течении вирусного заболевания. Легочные микозы протекают с высокой смертностью. Наиболее распространенным грибковым возбудителем, выявляемым у больных COVID-19 является Aspergillus spp. В связи расхождением в определениях и диагностических критериях, а также из-за неспецифических клинических проявлений, ассоциированный с COVID-19 легочной аспергиллез представляет затруднения как в диагностическом плане, так и с точки зрения ведения таких больны

Mutilating fungal infection - diagnostic surprise in a patient with post tuberculosis sequelae

Division of Pneumology and Allergology, Department of Internal Medicine, State University of Medicine and Pharmacy „Nicolae Testemițanu”, Chisinau, Republic of Moldova, Congresul consacrat aniversării a 75-a de la fondarea Universității de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica Moldova, Ziua internațională a științei pentru pace și dezvoltareIntroduction: Chronic pulmonary aspergillosis can mimic tuberculosis infection, but at the same time can be an overlapping complication of post-tuberculosis sequelae. Purpose: Highlighting the diagnostic difficulties of chronic cavitary pulmonary aspergillosis in a patient cured of disseminated tuberculosis. Material and methods: A 43-year-old patient, ex-smoker (54 p/y), immunocompetent, diagnosed with disseminated tuberculosis (pulmonary, intestinal, otitis) at the age of 40 (sensitive strain of M. tuberculosis confirmed bacteriologically). Clinical improvement was observed after 12 months of first-line antituberculous drug regimen. For the next 2 years he was monitored annually by chest X-ray and bacteriological examination of the sputum. Results: Relapse of tuberculosis infection was suspected in 2 years after completion of treatment, due to repeated episodes of hemoptysis, cough with purulent sputum (60 ml/day), weight loss of 6 kg during the lats 3 months, fatigue and night sweats. M. tuberculosis infection was excluded by negative molecular and bacteriological tests. Thoracic HRCT identified cylindrical bronchiectasis and a lung cavity with fungus ball in each upper lobe of the both lungs. The serum level of IgG for A.fumigatus within normal limits, no growth of any Aspergillus spp. has been identified by sputumculture. Empirical antifungal therapy with itraconazole resulted in improvement of the symptoms and the absence of hemoptysis episodes. Conclusions: The case highlights the diagnostic difficulties of fungal infections in a patient with post tuberculosis sequelae in a country with an increased incidence of tuberculosis infection within settings of limited accessibility tomodern diagnosticmethods for Aspergillus spp

Infecția fungică mutilantă - un diagnostic surprins la un pacient cu sechele posttuberculoase

Background. Chronic pulmonary aspergillosis can mimic tuberculosis infection, but at the same time can be an overlapping complication of post-tuberculosis sequelae. Objective of the study. Highlighting the diagnostic difficulties of chronic cavitary pulmonary aspergillosis in a patient cured of disseminated tuberculosis. Material and Methods. A 43-year-old patient, ex-smoker (54 p/y), immunocompetent, diagnosed with disseminated tuberculosis (pulmonary, intestinal, otitis) at the age of 40 (sensitive strain of M. tuberculosis confirmed bacteriologically). Clinical improvement was observed after 12 months of first-line anti-tuberculous drug regimen. For the next 2 years he was monitored annually by chest X-ray and bacteriological exa Results. Relapse of tuberculosis infection was suspected in 2 years after completion of treatment, due to repeated episodes of hemoptysis, cough with purulent sputum (60 ml/day), weight loss of 6 kg during the lats 3 months, fatigue and night sweats. M. tuberculosis infection was excluded by negative molecular and bacteriological tests. Thoracic HRCT identified cylindrical bronchiectasis and a lung cavity with fungus ball in each upper lobe of the both lungs. The serum level of IgG for A.fumigatus within normal limits, no growth of any Aspergillus spp. has been identified by sputum culture. Empirical antifungal therapy with itraconazole resulted in improvement of the symptoms and the absenc Conclusion. The case highlights the diagnostic difficulties of fungal infections in a patient with post tuberculosis sequelae in a country with an increased incidence of tuberculosis infection within settings of limited accessibility to modern diagnostic methods for Aspergillus spp. Introducere. Aspergiloza pulmonară cronică poate mima infecția tuberculoasă, dar în același timp poate fi o complicație suprapusă pe sechelele posttuberculoase. Scopul lucrării. Ilustrarea dificultăților de diagnostic într-un caz de aspergiloză pulmonară cronică cavitară la un pacient tratat de tuberculoză generalizată. Material și Metode. Un pacient de 43 ani, exfumător (54 p/an), imunocompetent, diagnosticat cu tuberculoză generalizată (pulmonară, intestinală, otită), vârsta de 40 ani (bacteriologic confirmată M. tuberculosis tulpină sensibilă). A urmat tratament antituberculos de linia I timp de 12 luni, cu ameliorare clinică. Următorii 2 ani a fost monitorizat anual prin radiografia toracelui și examen bacteriologic al sputei. Rezultate. Recidiva infecției tuberculoase a fost suspectată peste 2 ani de la finalizarea tratamentului prin apariția episoadelor repetate de hemoptizii, tuse cu spută purulentă 60 ml/zi, scădere ponderală 6 kg/3 luni, fatigabilitate, transpirații nocturne. Testele moleculare și bacteriologice din spută nu au confirmat infecția cu M. tuberculosis. HRCT toracică a identificat câte o cavitate pulmonară cu micetom în ambii lobi superiori și bronșiectazii cilindrice. Nivelul seric al IgG anti A. fumigatus în limitele normei. Nici o specie de Aspergillus nu a fost identificată prin sputocultură. Stoparea hemoptiziilor și ameliorarea simptomelor obținută prin tratament empiric cu itraconazol. Concluzii. Cazul pune în evidență dificultățile de diagnosticare a infecției fungice la un pacient cu sechele posttuberculoase, în condițiile accesibilității limitate la metodele moderne de diagnostic a speciilor de Aspergillus, într-o țară cu incidență sporită a infecției tuberculoase