The search for novel biomarkers in sepsis-induced cardiomyopathy – A new challenge to overcome

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and it remains the most frequent cause of death amongst critically ill patients worldwide, despite recent medical advancements. The cardiac involvement in sepsis, better known as sepsis-induced cardiomyopathy, represents a form of cardiac dysfunction identified in septic patients, characterized by ventricular dilation, myocardial involvement, decreased ejection fraction and reversibility. Although the implications of cardiac involvement in sepsis can be extremely severe, this affliction has not been intensely debated in literature. Therefore, in order to better understand this affliction, we need to identify new markers. Two biomarkers, endothelin-1 (ET-1) and the soluble form of suppression of tumorigenicity 2 protein (sST2) have previously been linked to both sepsis and acute/chronic heart failure. Endothelin-1 is part of a family of amino acid peptides, that is mainly produced by endothelial cells and exerts a vasoconstrictive effect, but also causes fibrosis of the vascular cells, stimulates production of reactive oxygen species and induces proinflammatory mechanisms. During sepsis, it induces coronary vasoconstriction, decreased cardiac output, increased vascular resistance and permeability and increased fluid flux into the extravascular space on cardiac level, as well as affecting the contractility of myocardial myocytes. High values of serum ET-1 have also been identified in septic shock and in endotoxin-induced febrile responses in rats. The Suppression of tumorigenicity 2 protein (ST2) is a member of the interleukin-1 receptor family and is involved in T helper 2 cells-associated immune response. Recent studies identified a close link between ST2 and both inflammatory and heart diseases. Furthermore, it was recently approved by the Food and Drug Administration as a prognostic biomarker in heart failure and is recommended for the evaluation of additional cardiovascular risk

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (similar to 5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted. (C) 2022 Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Post COVID-19 irritable bowel syndrome

Objectives: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. Design: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. Results: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p&lt;0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. Conclusion: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. Trial registration number: NCT04691895

TROMBOZA DE SINUS VENOS TRANSVERS STÂNG ASOCIATĂ MENINGITEI PNEUMOCOCICE LA COPIL – DIAGNOSTIC INTUITIV VS. COGNITIV

Introducere. Tromboza venoasă cerebrală (TVC) este o afecţiune cerebrovasculară rară cu multiple etiologii. Diagnosticul de TVC este în general obişnuit trecut cu vederea sau întârziat din cauza simptomatologiei extrem de variate, modalităţilor de debut şi semnelor neuroimagistice; mai mult, în peste 15% din cazuri, nu poate fi decelată o cauză, rezultatul individual poate fi greu de prezis, iar boala se poate complica în pofida tratamentului anticoagulant. Material şi metode. Prezentăm un caz tipic de meningită care în ziua 10 de boală asociază o simptomatologie nu foarte tipică ce pledează spre TVC. Rezultate. Examenele imagistice nu pot nici infirma, nici confirma prezenţa trombului. Un caz a cărui evoluţie se agravează progresiv şi pentru care nu există susţinerea imagistică de a aborda o anumită conduită terapeutică îngreunează decizia terapeutică a medicului. Discuţii. Problematica ridicată se concentrează pe ipoteza conform căreia dacă medicaţia anticoagulantă poate aduce un beneficiu pacientului sau, dimpotrivă, un prejudiciu medicului curant aflat în improbabilitate diagnostică, printr-o evoluţie ulterioară nefavorabilă a stării clinice a pacientului. Concluzii. Raţionamentul creierului uman format în ani de experienţă nu poate fi încă tehnologizat, cu atât mai puţin înlocuit de vreun robot, iar existenţa unor seturi de reguli de tratament, care nu pot acoperi niciodată varietatea de particularităţi ce se poate întâlni în practică, trebuie pusă întotdeauna la îndoială

INFECTIOUS ENDOCARDITIS WITH COXIELLA BURNETII

Q fever is caused by an anthropozoonosis determined by the pathogen Coxiella burnetii, a gram-negative bacterium with intracellular growth. The occurrence of infection in the human species takes place through inhalation of contaminated aerosols or dust from infected domestic animals (cattle, sheep, goats) and more rarely through ingestion of unpasteurized milk, infected mite or inter-human transmission. The endocardium is one of the main infection sites, especially in the context of the long-term development of the disease, and cardiac decompensation often leads to death in absence of a proper diagnosis and appropriate treatment (1). We present the case of a patient of the male sex aged 37 years without personal pathologic history known admitted in “St. Parascheva” Clinical Hospital for Infectious Diseases Iasi complaining of productive cough, fatigue, shortness of breath with moderate effort and pain in the left scapulohumeral joint with irradiation in the left upper limb. Clinical examination objectified digital clubbing, systolic/diastolic murmurs throughout the precordium area and hepato-splenomegaly, while laboratory tests revealed the presence of inflammatory syndrome, cholestasis and hepatic cytolysis. Echocardiography shows a hyperechogenic entity at the level of the aortic valve, as well as a severe valve disorder. The diagnosis of infective endocarditis is established on aortic valve and therapy with first-choice antibiotics, consisting of triple combination of cefotaxime, amikacin and vancomycin, is initiated. Blood cultures taken upon admission were negative, while positive serological phase I and II tests for C. burnetii urged the indication of changing therapy with doxycycline and trimethoprim sulfamethoxazole (in the absence of hydroxychloroquine). Subsequently he underwent aortic valve replacement. The particularities of this case consisted in atypical clinical manifestations, the absence of fever and epidemiological context suggestive for Q fever

ENDOCARDITA INFECŢIOASĂ CU COXIELLA BURNETII

Febra Q este o antropozoonoză determinată de patogenul Coxiella burnetii, o bacterie gram-negativă obligatoriu intracelulară. Apariţia infecţiei la specia umană se realizează prin inhalarea de aerosoli sau praf contaminat de la animalele domestice infectate (ovine, bovine, caprine) şi mai rar prin ingestie de lapte nepasteurizat, muşcătură de căpuşă sau interuman. Endocardul este unul dintre situsurile principale de localizare a infecţiei, mai ales în contextul unei evoluţii de lungă durată a bolii, iar decompensarea cardiacă duce frecvent la deces în absenţa unui diagnostic corect şi a unui tratament corespunzător (1). Vom prezenta cazul unui pacient de sex masculin, în vârstă de 37 de ani, fără antecedente personale patologice cunoscute, care se internează în Spitalul Clinic de Boli Infecţioase „Sfânta Parascheva“ din Iaşi acuzând tuse productivă, astenie marcată, dispnee la eforturi medii şi dureri la nivelul articulaţiei scapulohumerale stângi, cu iradiere în membrul superior stâng. Examenul clinic a obiectivat hipocratism digital, suflu sistolo-diastolic pe toată aria precordială şi hepatosplenomegalie, iar examenele de laborator au evidenţiat prezenţa sindromului inflamator, colestază şi hepatocitoliză. Ecocardiografic se vizualizează o formaţiune hiperecogenă la nivelul valvei aortice, precum şi disfuncţie valvulară severă. Se stabileşte diagnosticul de endocardită infecţioasă pe valvă aortică şi se instituie antibioterapia de primo-intenţie constând în tripla asociere cefotaxim, amikacină şi vancomicină. Hemoculturile recoltate la internare au fost negative, în schimb, pozitivarea testelor serologice de fază I, respectiv II pt C. burnetii au impus remanierea terapiei cu doxiciclină şi cotrimoxazol începând cu a zecea zi de spitalizare, cu evoluţie ulterioară favorabilă. Particularitatea cazului a vizat manifestările clinice atipice, absenţa febrei şi a contextului epidemiologic sugestiv pentru febră Q

LEFT TRANSVERSE VENOUS SINUS THROMBOSIS ASSOCIATED TO PNEUMOCOCCAL MENINGITIS IN CHILDREN – INTUITIVE VS. COGNITIVE DIAGNOSIS

Introduction. Cerebral venous thrombosis (CVT) is a rare cerebrovascular condition involving multiple etiologies. Diagnosis of CVT is usually overlooked or delayed due to highly varied symptomatology, modes of onset and neuroimaging signs; furthermore, the same cause cannot be found in more than 15% of the cases, individual result being hard to predict, while the disease can complicate despite anticoagulant treatment. Material and methods. We present a typical case of meningitis that in day 10 of illness associated an uncommon symptomatology suggesting cerebral venous sinus thrombosis (CVST). Results. It should be noted that imaging examination can neither confirm nor exclude a thrombosis. A case whose development worsens progressively and for which there is no imaging exam to support a particular therapeutic conduct hampers the decision-making process for the physician. Discussion. The issue raised focuses on the assumption that anticoagulant medication may be beneficial to the patient or, on the contrary, it may be in the detriment of the physician who is uncertain about the diagnosis, due to subsequent unfavorable development of patient clinical status. Conclusions. That human rational thinking, exercised in years of experience, cannot yet be technologized, let alone replaced by a robot, and the existence of sets of rules for treatment incapable to ever cover the variety of features encountered in practice must always be doubted

THE IMPORTANCE OF CLINICAL PICTURE IN THE DIAGNOSIS OF GUILLAIN-BARRÉ SYNDROME

Guillain-Barré syndrome (GBS) is an immune-mediated peripheral polyradiculonevritis, which is clinically characterized by rapid, symmetrical progression of muscle weakness or paralysis, with or without sensitive symptoms. We report the case of a male child aged 4 years is presented for distal weakness in the lower limbs, impossibility of maintaining vertical posture, balance disorders, alternating sleepiness with episodes of psychomotor agitation and dysphonia, headache, with sudden onset about 12 hours before hospitalization. The presented case underlines the importance of accurately describing the clinical picture and evolution in establishing the diagnosis, in total or partial absence of paraclinical data. Also, the low number of cases described in medical jurnals justify the interest in investigating and publishing these cases