Fetal Growth Restriction and Clinical Parameters of Newborns from HIV-Infected Romanian Women.

Background and Objectives: The present study assessed the fetal growth restriction and clinical parameters of both human immunodeficiency virus (HIV)-negative and HIV-positive newborns from HIV-infected mothers in two HIV-acquired immunodeficiency syndrome regional centers (RCs) in Constanta and Craiova, Romania, in order to evaluate the adverse birth-related outcomes. Materials and Methods: These represent a retrospective study conducted between 2008 and 2019, in which 408 pregnant HIV-positive women, 244 from Constanta RC and 164 from Craiova RC, were eligible to participate in the study. Consecutive singleton pregnancies delivered beyond 24 weeks of pregnancy were included. Growth restriction in newborns was defined as the birth weight (BW) being less than the third percentile, or three out of the following: BW < 10th percentile; head circumference (HC) < 10th percentile; birth length (BL) < 10th percentile; prenatal diagnosis of fetal growth restriction; and maternal pregnancy information. Of the 244 newborns delivered in Constanta, RC, 17 were HIV-positive, while in Craiova, RC, of the 164 newborns, 9 were HIV-positive. All HIV-positive women were on combined antiretroviral therapy (cART) during pregnancy, similar to all HIV-positive newborns who received ARTs for the first six weeks. We search for the influence of anthropometrical parameters (i.e., HC, BL, and BW), as well as clinical parameters (i.e., newborn sex and Apgar score) for both HIV-negative and HIV-positive newborns, along with the survival rate of HIV-positive newborns. Results: There were no differences in the sex of the newborns within either group, with more than 50% being boys. Similarly, the Apgar score did not show any statistically significant values between the two groups (i.e., p = 0.544 for HIV-positive newborns vs. p = 0.108 for HIV-negative newborns). Interestingly, our results showed that in Craiova, RC, there was a chance of 2.16 to find an HIV-negative newborn with an HC < 10th percentile and a 2.54 chance to find an HIV-negative newborn with a BL < 10th percentile compared to Constanta, RC, without any significant differences. On the contrary, Constanta, RC, represented a higher risk of death (i.e., 3.049 times, p = 0.0470) for HIV-positive newborns compared to Craiova, RC. Conclusions: Our results support the idea that follow-up of fetal growth restriction should be part of postnatal care in this high-risk population to improve adverse birth-related outcomes.

Characterization of sepsis inflammatory endotypes using circulatory proteins in patients with severe infection: a prospective cohort study.

BACKGROUND: Sepsis is a heterogeneous syndrome due to a variable range of dysregulated processes in the host immune response. Efforts are made to stratify patients for personalized immune-based treatments and better prognostic prediction. Using gene expression data, different inflammatory profiles have been identified. However, it remains unknown whether these endotypes mirror inflammatory proteome profiling, which would be more feasible to assess in clinical practice. We aim to identify different inflammatory endotypes based on circulating proteins in a cohort of moderately ill patients with severe infection (Sepsis-2 criteria). METHODS: In this prospective study, 92 inflammatory plasma markers were profiled using a targeted proteome platform and compared between patients with severe infection (Sepsis-2 criteria) and healthy controls. To identify endotypes with different inflammatory profiles, we performed hierarchical clustering of patients based on the differentially expressed proteins, followed by clinical and demographic characterization of the observed endotypes. RESULTS: In a cohort of 167 patients with severe infection and 192 healthy individuals, we found 62 differentially expressed proteins. Inflammatory proteins such as TNFSF14, OSM, CCL23, IL-6, and HGF were upregulated, while TRANCE, DNER and SCF were downregulated in patients. Unsupervised clustering identified two different inflammatory profiles. One endotype showed significantly higher inflammatory protein abundance, and patients with this endotype were older and showed lower lymphocyte counts compared to the low inflammatory endotype. CONCLUSIONS: By identifying endotypes based on inflammatory proteins in moderately ill patients with severe infection, our study suggests that inflammatory proteome profiling can be useful for patient stratification.

Aspects of Humoral Immunity after Vaccination with Bnt162b2: A Small Study.

Starting from December 2020, vaccination against COVID-19 became available in Romania. There are a lot of uncertainties regarding the kinetics of immunity and its persistance over time. This is a small prospective study developed between January-September 2021 in the Infectious Diseases Clinic from Craiova and comprising 61 subjects immunised with BNT162b2 (Comirnaty). We have found that after two doses of vaccine there is a strong humoral response, but the immunity lowers six months later. Subjects with a diagnosis of COVID-19, previously or in between the two doses, have had the most significant immunological response, but, also, the sharpest decline in antibody titer. The immune response seems to be the same, regardless the gender of the subjects. There are a variety of responses at the individual level, but overall vaccine effectiveness is 96.72% two weeks following immunisation and 88.52% after six months; however for those who have been in contact with the virus, they all had an antibody titer well above the laboratory limit.

Liver Function Tests and FIB-4 Score as Predictors of Severity in COVID-19 Patients from the South-West of Romania.

BACKGROUND: The coronavirus disease 2019 pandemic (COVID-19) is the most important global health crisis to date. In this study, we performed an analysis to find the association between liver damage, FIB-4 score and the severity of COVID-19 disease. METHODS: We included a total of 580 patients that tested positive for SARS-CoV-2 infection and were hospitalized. No patient included had any known history of liver disease. Liver function tests were performed, and FIB-4 score was calculated in order to assess their involvement in the disease progression. RESULTS: More than half of the patients had elevated liver function tests. Age, high body mass index, associated heart disease and diabetes were associated with poor outcome. Corticosteroids, antibiotics, and anticoagulants strongly correlated with liver injuries. Liver impairment and injury, as well as a FIB-4 score higher than 3.5, also correlated with higher degrees of disease severity. CONCLUSION: Liver injury and elevated FIB-4 score were associated with poor clinical outcome and disease severity, as well as being a valuable tool to predict COVID-19-related mortality.

Echocardiography Assessment of Cardiac Function in Adults Living with HIV: A Speckle Tracking Study in the Era of Antiretroviral Therapy.

Adults living with HIV (human immunodeficiency virus) infection (ALHIV) have high rates of cardiovascular events. New approaches are needed to detect subclinical cardiac dysfunction. We used conventional and speckle tracking echocardiography to investigate whether ALHIV display latent cardiac dysfunction. We analyzed 85 young subjects with HIV infection and free from cardiovascular risk factors (31 ± 4 years) and 80 matched healthy volunteers. We measured left ventricular (LV) layered global longitudinal strain, circumferential strain, peak longitudinal strain in the reservoir and contraction phases of the left atrium (LASr respectively LASct). In the HIV group, LV ejection fraction and s' TDI (tissue doppler imaging) were slightly lower but still in the normal ranges. Layered longitudinal strain showed no significant difference, whereas circumferential global strain was significantly lower in the HIV group (−20.3 ± 3.9 vs. −22.3 ± 3.0, p < 0.001). LASr (34.3% ± 7.3% vs. 38.0% ± 6.9%, p < 0.001) was also lower in ALHIV and multivariate analysis showed that age (ß = −0.737, p = 0.01) and infection duration (ß = −0.221, p = 0.02) were independently associated with LASr. In the absence of cardiovascular risk factors, adults living with HIV display normal LV systolic function. Left atrial reservoir strain, is, however, decreased and suggests early diastolic dysfunction.

Perinatal Exposure to HIV Infection: The Experience of Craiova Regional Centre, Romania.

BACKGROUND AND OBJECTIVES: HIV infection in pregnant women can be responsible for a number of consequences during pregnancy, such as: maternal anaemia, miscarriage, low birth weight, and preterm birth. The objectives of this study were to determine the maternal-foetal transmission rate of HIV among pregnant women living with HIV from Craiova Regional Centre in order to assess the risk factors for mother-to-child transmission of HIV and to identify the characteristics of newborns perinatally exposed to HIV. MATERIALS AND METHODS: A retrospective study was conducted between 1 January 2011 and 31 December 2020, including children born to HIV-positive mothers. RESULTS: The studied group included 138 newborns and was divided into two subgroups: group A, which included 10 HIV-infected infants; and group B, which included 128 uninfected infants. The mother-to-child transmission rate was 3.5% for women to whom all prophylaxis standards were applied. We found a statistically significant correlation between the level of maternal HIV viremia and perinatal HIV transmission (p = 0.01). Preterm birth and low birth weight were associated with perinatal transmission of the infection. CONCLUSIONS: Perinatal transmission of HIV infection during our study was associated with inconsistent application of screening for HIV infection among pregnant women, lack of antiretroviral therapy, poor adherence to treatment, and detectable HIV viral load during pregnancy.

Clinical and Biological Risk Factors Associated with Increased Mother-to-Child Transmission of HIV in Two South-East HIV-AIDS Regional Centers in Romania.

Background and Objectives: The occurrence of human immunodeficiency virus (HIV) infection in children in Romania has been reported since 1989. This retrospective study was aimed at assessing clinical and biological risk factors for mother-to-child transmission (MTCT) of HIV in two HIV-acquired immune deficiency syndrome (AIDS) Regional Centers (RCs), Constanta and Craiova in Romania. Materials and Methods: During the study period (2008-2019), 408 HIV-positive pregnant women, 244 from Constanta RC and 164 from Craiova RC who attended antenatal visits, were included. All HIV-positive pregnant women were under combined antiretroviral therapy (cART) during pregnancy and childbirth, being followedup with their infants up to 18 months after delivery. We investigated the clinical as well as biological risk factorsassociated with increased MTCT of HIV. Results: Comparing different variables of HIV-positive pregnant women from the two HIV-AIDS CRs, we find that there are significant differences between the mean value of hemoglobin, CD4 level, environmental area, marital and amniotic membranes status, and HIV patient stage in the last trimester of pregnancy (p < 0.05), but without any differences in mother's mean age, education level, type of delivery, breastfeeding, the duration of cART administration, HIV viral load, and survival rate. Conclusions: In 408 HIV-positive pregnant women followed up at two HIV-AIDS RCs in Romania, the most important clinical and biological risk factors associated with increased MTCT of HIV are represented by anemia, CD4 level, and HIV patient stage.

Electrochemical monitoring of bronchial inflammation in pediatric athletes: A prospective study.

The assessment of inflammation by accessible, reproducible and especially non-invasive methods is one of the main goals for numerous medical specialties. One variable for assessment is the fraction of nitric oxide in exhaled air (FeNO), which correlates with the inflammatory syndrome of the airways. The objective of the present study was the biochemical evaluation of FeNO in children practicing sports in Oltenia, Romania. Between January and December 2018, children practicing sports (football, track and field, judo, fencing, handball, volleyball and basketball) were enrolled in the study. The FeNO values were compared with the asthma history and with the spirometric evaluation. A total of 23 children without a previous asthma diagnosis exhibited positive spirometry results. The prevalence of the disease was 3.6% in the cohort, and FeNO dosing showed higher values in the group at risk in children diagnosed with asthma, compared with that in children without this diagnosis. The children who performed outdoor sports (soccer, and track and field) had higher electrochemical levels of nitric oxide compared with those who performed indoor sports (mean, 29.70 vs. 20.56; P<0.0005), which led to the hypothesis that these children had an increased risk of developing bronchospasm. FeNO dosing can thus be a useful and easy-to-use tool in practice for assessing bronchial inflammation in children practicing various types of sports. The spirometric data of undiagnosed asthma patients from the present study may indicate that the disease is still underdiagnosed within Romania.

The Role of QuantiFERON-TB Gold Plus in Mycobacterium Tuberculosis Detection in a Severe HIV Immunocompromised Patient-Case Report.

Tuberculosis (TB) is an important opportunistic infection in HIV-positive people. We are reporting a case of a 31-year-old HIV-infected patient who was hospitalized in July 2021 for dyspnea, cough with mucopurulent sputum and asthenia. He was confirmed to have Serratia liquefaciens pneumonia and acute respiratory failure. The evolution was unfavorable despite the antibiotic, pathogenic and symptomatic treatment. Because the patient had severe immunosuppression (CD4 count = 37 cell/mm3), we used QuantiFERON-TB Gold Plus for the detection of the Mycobacterium tuberculosis infection. The antituberculosis therapy was initiated, which resulted in a significant improvement of the general condition and the patient was discharged with the recommendation to continue antiretroviral therapy, antituberculosis treatment and Trimethoprim/Sulfamethoxazole-single tablet daily for the prophylaxis of Pneumocystis pneumonia.

Lemierre's Syndrome: Case Presentation of a Rare and Possibly Life-Threatening Condition.

Lemierre's syndrome is, presently, a very rare condition, but a life-threatening one. The syndrome was first described in 1936 by Andre Lemierre and comprises an oropharyngeal infection (most commonly associated with anaerobic bacteria Fusobacterium necrophorum), internal jugular vein thrombophlebitis and, possibly, secondary septic metastasis (common sites are lungs or brain). We describe such a rare case diagnosed at our Infectious Diseases Department in September 2019.

Quality of life in people living with HIV in Romania and Spain.

BACKGROUND: Health-related quality of life (HRQoL) is a crucial component in assessing and addressing the unmet needs of people, especially those with chronic illnesses such as HIV. The aim of the study was to examine and compare the health-related quality of life of people living with HIV in Romania and Spain, compared to the general populations of each country. METHODS: A cross-sectional survey was conducted among adults (≥ 18 years) attending for HIV care in Romania and Spain from October 2019 to March 2020. The survey included two validated HRQoL instruments: a generic instrument, EQ-5D-5L, and an HIV-specific instrument, PozQoL, and questions on socio-demographics, HIV-related characteristics, physical and mental health conditions, and substance use. Multivariable linear regression was used to determine factors associated with HRQoL. RESULTS: 570 people living with HIV responded (170 in Romania and 400 in Spain). The median age was 31 (18-67) in Romania and 52 (19-83) in Spain. Anxiety/depression symptoms were frequently reported by people with HIV (Romania: 50% vs 30% in the Romanian population; Spain: 38% vs 15% in Spanish population). Spain reported higher mean EQ-5Dutility scores than Romania (0.88 and 0.85, respectively) but identical PozQoL scores (3.5, on a scale of 0-5). In both countries, health concerns were highlighted as a key issue for people with HIV. In multivariable analysis, two factors were consistently associated with worse HRQoL in people with HIV: bad or very bad self-rated health status and presence of a mental health condition. In Romania, being gay/bisexual and being disabled/unemployed were associated with worse HRQoL. Whereas in Spain, older age and financial insecurity were significant predictors. CONCLUSIONS: Our results indicated a good HRQoL for people living with HIV in Romania and Spain; however, worse HRQoL profiles were characterized by health concerns, poor self-rated health status, and the presence of mental health conditions. This study highlights the importance of monitoring HRQoL in people living with HIV due to the chronic nature of the disease. In this highly-treatment experienced group, disparities were found, particularly highlighting mental health as an area which needs more attention to improve the well-being of people living with HIV.

Analysis of the First 300 Cases of SARS CoV2 Infection from the Infection Disease Clinic of Craiova, Romania.

COVID-19 is an ongoing pandemic and an intermediate analysis of the first 300 cases treated in the Infectious Diseases Clinic from Craiova has been performed. We have found that most of the cases were asymptomatic or mild, but the severity of the symptomatic cases increases with age. The main comorbidities associated mainly with the severe cases were high blood pressure, obesity, other cardiac conditions, diabetes mellitus and malignancies. Inflammation, coagulation and metabolic disorders are significantly more expressed in critically ill patients. Fatality rate is relatively low, death seems to be associated with old age.

Human Anthrax in Dolj County, Romania-A Series of Three Cases.

Bacillus anthracis is the causative agent of anthrax, primarily a disease of herbivorous animals, which can be accidentally transmitted to humans. Three cases of cutaneous human anthrax were recorded in August 2020 in Dolj county, Romania. These cases included livestock farmers (husband and wife, as well as a man from their entourage). The women presented malignant edema, which required surgery for compartment syndrome; and the men presented the common form of cutaneous anthrax. According to the laboratory investigation, two cases complied with the criteria in the case definition. All cases were successfully treated with antibiotics and the women received reconstructive plastic surgery of the skin defects, restoring normal hand function. The contact with sick animals was ruled out by the health authorities concluding that it was the contamination of pre-existing skin lesions with B. anthracis spores from the soil, the anthracogenic area.

Influence of multidisciplinary therapeutic approach on fibromyalgia patients.

There is no specific cure for fibromyalgia (FM), but combined non-pharmacologic and pharmacologic treatments may mitigate symptoms and improve quality of life in patients. The aim of the present study was to monitor patient response to several types of therapy, including cognitive-behavioral and occupational therapy, and kinetic therapy, as compared to a control group that was not subjected to any form of therapy. The study included 98 FM patients, all women, out of which 32 received cognitive-behavioral therapy and occupational therapy (CBT+OT), 34 kinetic therapy (KT) and 32 participated as controls. The evaluation protocol comprised two questionnaires developed in order to assess the patient's condition as fully as possible: Fibromyalgia Impact Questionnaire (FIQ) and Fibro Fatigue (FF) scale. At the pre-evaluation there were no significant inter-group differences. At post-evaluation significant differences were observed between the control sample and the group subjected to kinetic therapy (P<0.05). FIQ scores decreased in the CBT+OT group too, but less than that in the KT group. The FF scale registered notable evolutions in time for the group subjected to kinetic therapy. In order to control and improve most of the FM symptoms, besides proper medication, we suggest an interdisciplinary intervention mainly focusing on long-term individualized kinetic therapy. The simultaneous integration of a cognitive-behavioural and occupational therapy intervention could be the element that completes the complex treatment of FM patients.

The characteristics of HIV-positive patients with mild/asymptomatic and moderate/severe course of COVID-19 disease-A report from Central and Eastern Europe.

BACKGROUND: There is currently no evidence suggesting that COVID-19 takes a different course in HIV-positive patients on antiretroviral treatment compared to the general population. However, little is known about the relation between specific HIV-related factors and the severity of the COVID-19 disease. METHODS: We performed a retrospective analysis of cases collected through an on-line survey distributed by the Euroguidelines in Central and Eastern Europe Network Group. In statistical analyses characteristics of HIV-positive patients, asymptomatic/moderate and moderate/severe course were compared. RESULTS: In total 34 HIV-positive patients diagnosed with COVID-19 were reported by 12 countries (Estonia, Czech Republic, Lithuania, Albania, Belarus, Romania, Serbia, Bosnia and Herzegovina, Poland, Russia, Hungary, Bulgaria). Asymptomatic courses of COVID-19 were reported in four (12%) cases, 11 (32%) patients presented with mild disease not requiring hospitalization, moderate disease with respiratory and/or systemic symptoms was observed in 14 (41%) cases, and severe disease with respiratory failure was found in five (15%) patients. The HIV-related characteristics of patients with an asymptomatic/mild course of COVID-19 were comparable to those with a moderate/severe course of COVID-19, except for the use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in cART regimen (0.0% vs. 31.6% respectively, p = 0.0239). CONCLUSIONS: In our analyses HIV viral suppression and immunological status were not associated with the course of COVID-19 disease. On the contrary the cART regimen could contribute to severity of SARS-CoV-2 infection. Large and prospective studies are necessary to further investigate this relationship.

Clinico-pathological study of chronic rhinitis in adolescents.

Through the increasing incidence and association of asthma, chronic rhinitis (CR) raises major problems in the pathology of children and adolescents. The evaluation of the inflammatory status together with the diagnosis and the tandem treatment of the two conditions can contribute to the improvement of the patients' quality of life. In this study, we analyzed the immunoexpression of cluster of differentiation (CD) 20, CD8, CD138 and eosinophil major basic protein (MBP) in 24 cases of CR in adolescents, in eight of them existing the association of asthma. Symptoms of CR and allergic status, as well as histopathological changes specific to a persistent inflammation, were identified in this study. The CD20∕CD8 immunophenotype was more specific for CR, while the CD138∕eosinophil MBP immunophenotype was specific for asthma-associated chronic rhinitis (AACR). The negative linear distribution of lymphocyte elements compared to plasmocytes and eosinophils specific for the allergic status can support the protective effect of CD8 T-lymphocytes and the presence of a semi-activated B-lymphocyte status in CR. The results may be useful for improving the stratification criteria of patients for therapy.

Considerations About Risk Factors for Peripheral Neuropathies in Romanian HIV-Infected Patients.

PURPOSE: The study aims at detecting risk factors for developing peripheral neuropathy in Romanian HIV infected subjects. MATERIAL/METHODS: retrospective study (january 1990-january 2009) who analyzed data from patients hospitalized in the Regional Center Craiova. We have compared 26 patients (group N) diagnosed with peripheral neuropathy  with 40 patients (group C) without neuropsychological sufferings, randomly selected. We have analysed: age, height, HIV mode of transmission, AIDS status, the average and nadir of CD4 lymphocytes, the mean viral load, the average duration of antiretroviral treatment (ART), use and duration of use of d-drugs, the presence of certain coinfection, diabetes or ethanol abuse. RESULTS: the following differences were statistically significant: age (31,54±14,64 vs 23,9±12,03 years, p=0.024), HIV mode of transmission  (parenteral/sexual: 13/13 vs 28/8, p = 0.044), the monitoring time duration (5,31±3,77 vs 7,75±5,4 years, p=0.043), median ART duration (37,2±9,66 vs 45,12±8,75 months, p=0.001). Close to the threshold of statistical significance are the CD4 nadir (97,33±65,6 vs 123,15±43,35 cells/mm3, p=0.058) and duration of use of d-drugs (22,5±31,94 vs 12,24±8,6 months, p=0.057). Odds ratio (OR) and relative risk (RR) increase with age. ROC analysis for the study group establishes a threshold difference of 29 years (sensitivity 50%, specificity 80%). CONCLUSIONS: higher age and advanced immunosupression are the most important risk factors for developing symptomatic peripheral neuropathy in Romanian HIV infected patients; taking into account the small number of cases studied, although not statistically significant, it should be noted the CD4 nadir and the length of d-drug use.

HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood.

BACKGROUND: There are few studies on pediatric HIV-HBV coinfection, so evidences about relationships between the two viruses are scarce. OBJECTIVES: influence of HBV infection on virological and immunological response to antiretroviral therapy (ART) in antiretroviral-naïve horizontally HIV-HBV coinfected subjects during early childhood. MATERIAL AND METHODS: observational study on 826 HIV+ subjects in evidence of Craiova Regional Centre (CRC); we analyzed the immunological and virological response at 6-12 months after starting first antiretroviral regimens compared in 2 groups: horizontally HIV-HBV coinfected subjects during early childhood (CoS) versus horizontally HIV infected subjects during early childhood without HBV infection (non-CoS). RESULTS: Number of subjects: CoS-66 subjects, non-CoS-132 subjects. Demographic data: CoS-gender ratio F:M=0.886, the majority lived in rural area (57.58%), mean age on diagnosis-9.288±4.607 years, non-CoS-gender ratio F:M=0.859, the majority lived in urban area (53.79%), mean age on diagnosis-10.742±5.107 years. At baseline, HIV category was: CoS-A-1.52%, B-80.30%, C-18.18%, non-CoS-A-2.27%, B-70.45%, C-27.27% (p Chi(2)=0.332), the mean CD4+ cell count was: CoS-148.33±148.10 cells/ml, non-CoS-163.17±155.39 cells/ml (p Student=0.521) and the mean HIV viral load (HIV VL) was: CoS-5.06±0.80 lgcopies/ml (for 29 subjects), non-CoS-5.04±0.84 lgcopies/ml (for 61 subjects) (p Student=0.978). At the end of the studied period, the mean increase in CD4+ cell count was: CoS-177.068±141.676 cells/ml, non-CoS-176.015±191.751 cells/ml (p Student=0.969) and the mean decrease in HIV VL was: CoS-5.04±0.79 lgcopies/ml, non-COS-4.69±2.04 lgcopies/ml (p Student=0.911). CONCLUSIONS: The presence of HBV coinfection does not influence immunological or virological response to ART.