Antiretroviral Therapy Switch in HIV-Infected Adults from a Regional HIV/AIDS Center in NE Romania.

Background and Objectives: Antiretroviral therapy (ART) has revolutionized the management of HIV infection, transforming it from a once-debilitating disease to a chronic, manageable condition. However, challenges such as treatment resistance, medication side effects, and long-term tolerability persist, prompting the exploration of novel therapeutic approaches. We aimed to highlight the characteristics and related comorbidities of HIV/AIDS cases in which the antiretroviral therapy was modified. Material and Methods: A cross-sectional clinical investigation was conducted on adults diagnosed with HIV/AIDS who were hospitalized at the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi in the Northeastern region of Romania. The timeframe under investigation was 1 January 2023 to 30 June 2023. Results: In the Northeastern part of Romania, from a total of 1692 patients in the active records, there were a total of 148 recorded cases of antiretroviral therapy switch in HIV-infected patients. The main reason for the ART switch was the simplification of the ART regimen (82 cases, 55.40%), viro-immunological failure (16 cases, 10.66%), other disturbances correlated to the ART regimen, dyslipidemia (34 cases 22.97%), depression (3 cases, 2.02%), suicide attempt (1 case, 0.67%), new situations, including the appearance of pregnancy (3 cases 2.02%), and tuberculosis (9 cases, 6.08%). ART before the switch was represented by protease inhibitors that accounted for 84 cases (56.75%) of the ART switch. Following the therapy switch, integrase inhibitor-based ART single-tablet regimens accounted for 43.91% (65 cases) of all changeovers, with non-nucleoside reverse transcriptase inhibitor regimens coming in second, in 63 cases, 42.66%. Conclusions: ART switch as an experimental therapy offers a promising approach to optimizing HIV treatment outcomes. By focusing on viral suppression and immune reconstitution, addressing treatment challenges, and exploring novel ARV agents, ART switch strategies aim to improve the overall health and well-being of individuals living with HIV.

The Impact of Urinary Catheterization on the Antibiotic Susceptibility of ESBL-Producing Enterobacterales: A Challenging Duo.

INTRODUCTION: Antimicrobial resistance (AMR) is currently a growing concern among healthcare providers, underscoring the importance of describing the regional susceptibility profile for common microorganisms that are associated with urinary tract infections (UTIs). This knowledge serves as the foundation for proper empirical therapeutic recommendations tailored to local susceptibility patterns. RESULTS: We found a high prevalence of ESBL-producing strains (36.9%), with Escherichia coli and Klebsiella spp. being the most prevalent isolated bacteria. Among the catheterized patients, Klebsiella spp. emerged as the primary etiology, with a significant correlation between catheterization and Proteus spp. (p = 0.02) and Providencia stuartii (p < 0.0001). We observed significant correlations between urinary catheterization and older age (68.9 ± 13.7 years vs. 64.2 ± 18.1 years in non-catheterized patients, p = 0.026) and with the presence of an isolate with extensive drug resistance (p < 0.0001) or even pandrug resistance (p < 0.0001). Susceptibility rates significantly decreased for almost all the tested antibiotics during the study period. Notably, susceptibility was markedly lower among catheterized patients, with the most pronounced differences observed for carbapenems (59.6% versus 83.4%, p < 0.0001) and aminoglycosides (37.1% versus 46.9%, p = 0.0001). MATERIALS AND METHODS: We conducted a retrospective study analyzing the susceptibility profiles of 724 extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales isolated from urine cultures. Our focus was on highlighting susceptibility profiles among isolates associated with urinary catheterization and assessing the shifts in the susceptibility rates over time. CONCLUSIONS: The constant rise in AMR rates among Enterobacterales presents significant challenges in treating severe infections, particularly among urinary catheterized patients. This trend leaves clinicians with limited or no effective treatment options. Consequently, the development and implementation of personalized treatment protocols are imperative to ensure efficient empirical therapies.

Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Literature Review.

Hospital-acquired pneumonia (HAP) and its subtype, ventilator-associated pneumonia (VAP), remain two significant causes of morbidity and mortality worldwide, despite the better understanding of pathophysiological mechanisms, etiology, risk factors, preventive methods (bundle of care principles) and supportive care. Prior detection of the risk factors combined with a clear clinical judgement based on clinical scores and dosage of different inflammatory biomarkers (procalcitonin, soluble triggering receptor expressed on myelloid cells type 1, C-reactive protein, mid-regional pro-adrenomedullin, mid-regional pro-atrial natriuretic peptide) represent the cornerstones of a well-established management plan by improving patient's outcome. This review article provides an overview of the newly approved terminology considering nosocomial pneumonia, as well as the risk factors, biomarkers, diagnostic methods and new treatment options that can guide the management of this spectrum of infections.

Liver Damage Associated with SARS-CoV-2 Infection-Myth or Reality?

(1) Introduction: While the primary impairment in COVID-19 is pulmonary, the ubiquitous distribution of angiotensin-converting enzyme 2 (ACE2) demonstrates the possible presence of systemic disease with involvement of the heart, kidneys, liver and other organs. (2) Methods: We retrospectively studied the observation sheets of patients diagnosed with SARS-CoV-2 infection hospitalized in the "Sf. Parascheva" Clinical Hospital of Infectious Diseases from Iasi for a period of 3 months. The aim of the study was to identify the frequency of liver injury due to SARS-CoV-2 infection among patients and its impact on the course of the disease. (3) Results: Out of the total number of hospitalized cases (1552), 207 (13.34%) were the subjects of our analysis. The severe form of SARS-CoV-2 infection predominated (108 cases; 52.17%) and in terms of liver damage, in all cases increased transaminase levels predominated and were determined to be secondary to the viral infection. We divided the lot into two groups, A (23 cases; 23.19%) and B (159 cases; 76.81%), depending on the time of onset of liver dysfunction, either at the time of hospitalization or during hospitalization. The evolution of liver dysfunction was predominant in most cases, with an average time of onset at 12.4 days of hospitalization. Death occurred in 50 cases. (4) Conclusions: This study revealed that high AST and ALT at hospital admission was associated with a high mortality risk in COVID-19 patients. Therefore, abnormal liver test results can be a significant prognostic indicator of outcomes in COVID-19 patients.

Seroprevalence of Anti-Hepatitis E Virus Antibodies among Patients from a Tertiary Hospital from Northeast Romania.

Background and Objectives. Being an enterically transmitted pathogen with a growing prevalence in developed countries, hepatitis E virus (HEV) infection remains an underdiagnosed disease in Eastern Europe. As far as Romania is concerned, only a few studies address this issue. Our goal was to estimate the prevalence of serum anti-HEV IgA/IgM/IgG antibodies in a group of patients admitted to the Clinical Hospital for Infectious Diseases "St. Parascheva" Iasi. Materials and Methods. The cross-sectional study consisted of enrollment of 98 patients admitted to the clinic for COVID-19 over a period of three months in 2020. Results. The median age in our study was 73 years, with an equal gender ratio and with a predominance of people from the urban environment (75%). The overall HEV antibody seroprevalence was 12.2%. The main risk factors associated with HEV infection were consumption of water from unsafe sources (58.3% HEV-positive patients vs. 26.7% HEV-negative patients, p = 0.026) and improperly cooked meat (58.3% HEV-positive patients vs. 23.2% HEV-negative patients, p = 0.01). Zoonotic transmission was an important criterion in our study, with patients reporting contact with pigs, poultry, rats, or other farms animals, but no significant differences were found between HEV antibody positive and negative groups. Conclusions. The seroprevalence rate of HEV antibodies was similar to other previous reports from our area but higher than in most European countries. The fact that HEV antibodies were detected in patients without identifiable risk factors for hepatitis E is evidence of subclinical infection as a silent threat.

Clinical significance of early IgA anti-SARS-CoV-2 antibody detection in patients from a Romanian referral COVID-19 hospital.

Controlling the spread of coronavirus disease 2019 (COVID-19) includes institute isolation, quarantine measures and appropriate clinical management, which all require effective screening, diagnostic and prognostic tools. The present study aimed to analyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin (Ig)A detection and determine the potential association with the clinical course of COVID-19 and the levels of inflammation. In the present study, the presence of IgA and IgG SARS-CoV-2 antibodies in 75 consecutive patients with confirmed COVID-19 infection was investigated. No significant differences were found between the IgA positive and negative groups, regarding the presence of symptoms, haematological and inflammatory variables, or the presence of pneumonia. In the majority of cases, antibody detection was comparable, for example, 79.7% of patients in the IgA positive group exhibited both types of antibodies, while 80.9% of patients in the IgA negative group were also IgG negative. A total of four patients in the IgA negative group presented with anti-SARS-CoV-2 IgG antibodies. Early detection of IgA was more frequent in patients who later developed severe forms of the disease. In addition, the IgG SARS-CoV-2 antibody response was higher in patients with the severe form of the disease.

Concomitance or consequence? Stevens-Johnson syndrome in COVID-19: A case report.

The novel coronavirus infection has been, and still is, a pressing medical problem with a catastrophic effect, not only from a medical point of view, but also from an economic and social one. The cutaneous manifestations of the disease have a diverse morphology and can signal the presence of the infection. The present article reports the case of a 77-year-old male patient admitted at The Sf. Parascheva Clinical Hospital of Infectious Diseases in Iasi (Romania) after testing positive for SARS CoV-2 infection. Initially, the patient presented a pruriginous generalized maculopapular-erythematous eruption with a tendency towards confluence, peri-oro-nasal meliceric crusts and desquamation of the skin on the third anterosuperior and posterior thorax, scalp and forehead, which was accompanied by low back pain, headache and orbital pain. The suspicion of Stevens-Johnson syndrome (SJS) was raised, and treatment was given according to the recommendation of the hospital dermatologist. This association raises multiple questions regarding whether SJS is a cutaneous manifestation of COVID-19 or if there was a concomitance between the viral infection and the immune reaction. The combination of SJS and COVID-19 can have a fatal outcome if not recognized and promptly treated. To our knowledge, this is the first case of SJS in a patient diagnosed with SARS CoV-2 infection in Romania.

Death anxiety and burnout in intensive care unit specialists facing the COVID-19 outbreak: The mediating role of obsession with COVID-19 and coronaphobia.

The aim of the study was to examine the role of the obsession with COVID-19 thoughts and coronaphobia in the relationship of death anxiety with burnout among staff working at infectious diseases hospitals in the front-line of the fight against COVID-19. A cross-sectional online survey (N = 110) was conducted during the second wave of the COVID-19 pandemic. Results showed that obsession with COVID-19 and coronaphobia mediated the relationship of death anxiety with burnout. Most of the participants reported higher levels of death anxiety compared with the general population and nurses reported higher levels of death anxiety than physicians.

Enterically transmitted hepatitis in the third millennium in northeastern Romania.

While the incidence of hepatitis A virus (HAV) infections has decreased in the last few years, the incidence of hepatitis E virus (HEV) is increasing in developed countries. Both infections remain a worldwide reality, strongly related to socio-economic conditions. We retrospectively analyzed the medical files of patients with viral hepatitis hospitalized in the Infectious Disease Hospital Iasi, Romania between 2018 and 2019. The serological confirmed cases of HAV and HEV infections were included in the analysis; included in our analysis were 269 HAV-infected patients. The most affected were males (53.9% cases) aged between 8 and 15 years (53.6% cases). Severe infections were recorded at admission in 2.24% cases and evolution was favorable under supportive and symptomatic treatment. Only three adult males, with no recent history of travel, were confirmed with HEV infection. Even though we have identified a small number of cases, recent studies performed in our region found a seroprevalence of 32.5% in the general population, possibly related to zoonotic transmission. While outbreaks of HAV infection are still noted in our region, a lack of hospitalized HEV-infected patients suggest that most cases are asymptomatic or underdiagnosed. HEV infection remains an underreported disease, possibly due to misdiagnosis, subclinical or dual hepatitis infection, but with a significant risk in vulnerable categories, such as pregnant women or immunosuppressed patients.

SARS-CoV-2 infection and diabetes mellitus: A North Eastern Romanian experience.

As it spread globally, the new SARS-CoV-2 virus was first confirmed in Romania in February 2020, inevitably infecting individuals with diabetes mellitus (DM) along the way. Diabetes is known to affect the response of the body to pathogens and, according to studies conducted in the last 3 months, it appears that diabetic patients are at a higher risk for developing severe forms of the disease and multiple complications. We performed a retrospective study in order to assess the patients with SARS-CoV-2 infection and DM admitted to 'Sf. Parascheva' Clinical Hospital of Infectious Diseases from March 4th until June 30th, 2020. Of the total 1,080 patients admitted during this period, 85 patients (7.87%) had underlying DM, mostly type 2 (82 cases, 96.46%); the mean age of these patients was 62, and 42 were men (49.41%). Chest CTs revealed indicative SARS-CoV-2 images for all patients and their treatment included individually tailored administration of hydroxychloroquine/lopinavir + ritonavir/enoxaparin sodium/tocilizumab/antibiotherapy according to the then national and international guidelines. In total, 70 patients (82.35%) were cured and 15 succumbed to MODS and/or associated neoplasia, bringing the fatality rate to 17.64%. Although advanced age and DM have been associated with aggravated forms of SARS-CoV-2 infection, over 80% of the patients included in the present study were cured. Nonetheless, diabetes appears to be a significant predictor of morbidity and mortality in the SARS-CoV-2 infection.

Adult-onset Still's disease and the role of dermatological manifestations: A case report and literature review.

Adult-onset Still's disease (AOSD) is a rare inflammatory systemic disease with unknown etiology, characterized by spiking fever, evanescent rash, arthralgia and arthritis, leukocytosis and possible multi-organ involvement. Based on a case report of a 19-year-old man who was admitted to hospital for an influenza-like syndrome associated with a transient and recurrent pale-red disseminated non-specific rash, we performed a PubMed database search for cases and reviews of Adult's Onset Still's Disease published in English in the last 5 years. Due to its heterogeneous clinical manifestations, of which skin rash is an important sign, and the lack of a specific laboratory test, the diagnosis requires the exclusion of a wide range of mimicking disorders and the use of specific scoring systems. The high ferritin levels, major leukocytosis with neutrophilia, absence of typical antibodies for other systemic autoimmune diseases and other markers of infectious disease were the milestones that led to the positive diagnosis. The first line of treatment remains corticosteroid therapy in association with disease-modifying anti-rheumatic drugs.

A decreasing trend in toxoplasma gondii seroprevalence among pregnant women in Romania - results of a large scale study.

Toxoplasmosis is a zoonotic infection caused by the obligate intracellular apicomplexan parasite Toxoplasma gondii (T. gondii). T. gondii infection is a cause of congenital infection worldwide. Primary infection or the reactivation of latent infection during pregnancy may lead to fetal infection and to congenital toxoplasmosis syndrome. Seropositive pregnant women are generally protected from maternal-fetal transmission of T. gondii, although exceptions exist. The aim of our study was to analyze the dynamics of T. gondii seroprevalence during a 10-year period and to correlate it with age and demographic features of pregnant women. We tested 6,889 pregnant women in Timisoara, Romania, for IgG-anti-T. gondii antibodies, in two successive periods: i) 2008-2010 (group 1: 1,457 participants); and ii) 2015-2018 (group 2: 5,432 participants). For each participant, data on age and area of residence were collected. Our results showed that in the Western Region of Romania T. gondii seroprevalence in pregnant women declined from 43.79 to 38.81% in the last ten years. This trend was observed in both urban (40.53 vs. 34.85%) and rural areas (52.22 vs. 46.22%). A higher seroprevalence rate was found in rural than in urban areas. In addition, we found an increasing tendency of seroprevalence related to the age of pregnant women.

Anosmia and ageusia associated with coronavirus infection (COVID-19) - what is known?

In 2020 a new pandemic caused by the SARS-CoV-2 coronavirus is affecting the lives of millions of patients and healthcare workers worldwide. The clinical picture of this infection is in a dynamic process of discovery, and more symptoms emerge as the clinicians observe and diagnose manifestations that affect multiple organs. Anosmia (loss of smell), and ageusia (loss of taste) become more frequently cited as independent symptoms or in association with the most common manifestations of the disease, such as fever, cough and dyspnea. A thorough screening program will prevent most nosocomial and community-acquired infections by promoting efficient triage and specific measures such as isolation of the patients. Therefore, it is important to include frequent symptoms in the anamnesis and questionnaires to select those patients who might benefit from testing, isolation, and treatment. This study summarizes the existing data regarding the association of anosmia and ageusia with the SARS-CoV-2 infection. It also aims to describe manifestations of these, particularly in the clinical picture of all symptomatic patients.

Attitudes, practices, and priority of HIV screening and testing among clinical providers in Transylvania and Moldavia, Romania.

Screening and linkage to care are core, foundational strategies for HIV transmission prevention and for identifying People Living with HIV (PLHIV). In Romania - with an atypical experience in the HIV/AIDS epidemic - providing care for HIV+ patients identified early is a priority, though screening and testing can pose a challenge in some areas. METHODS: A survey of 125 clinical providers to explore important dimensions of HIV/ AIDS clinical care was conducted in Transylvania and Moldavia, where clinicians identified poor/ latent screening as a major problem in providing timely care and in preventing the spread of disease. We analyzed determinants of offering HIV screening/testing to patients using Pearson Chi-square analysis and logistic regression. Logistic regression generated Odds Ratios (OR) to reflect the magnitude of association between the relevant variables, with 95% confidence interval (95% CI) indicating statistical range. RESULTS: In total, 40.8% of providers did not provide HIV screening/testing to at least one segment of the population. Hospital-based providers were significantly more likely to offer HIV screening/testing to all segments than were non-hospital-based providers (58.1% v. 35.5%, respectively; p < .05). Providers located within institutions with screening/testing policies were more likely to offer such services to their patients (p < .05). Overall, 94.4% of providers indicated interest in more training around HIV screening/testing. DISCUSSION: Reaching Romanian and global goals for reducing HIV require more timely screening and action based on positive status. Romanian clinicians are interested in expanding HIV screening/testing and are interested in participating in training that helps them feel more prepared to undertake this work.

Access to digital and social media among Romanian HIV/AIDS clinical providers.

The WHO/UNAIDS suggests that digital tools - such as social media and online training opportunities, can connect providers in difficult social and medical contexts to providers elsewhere for guidance, support, and advice. Social media is emerging as an innovative option for connecting clinicians together and for enhancing access to professional resources. In Romania, characterized by an atypical HIV/AIDS epidemic which is further challenged by a range of access complexities, it is unclear how often - and which kinds of - social media clinicians use to support clinical care. This study was conducted to ascertain social media use for clinical providers based in two regions of Romania (Transylvania and Moldavia) who face distance challenges that could potentially be alleviated by social media interaction. We used an online survey to understand what social media are currently popular and perceived to be useful for learning clinical information. Descriptive and bivariate analyses were conducted. Providers indicated Facebook and WhatsApp were the most common social media platforms, with 62% and 45% reporting daily use, respectively. Providers who used one media platform were significantly more likely to use another social media platform (p < .05). These data are helpful for creating an online training platform on HIV/AIDS for Romanian clinical providers.

NADPH OXIDASE: STRUCTURE AND ACTIVATION MECHANISMS (REVIEW). NOTE I.

NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase), with its generically termed NOX isoforms, is the major source of ROS (reactive oxigen species) in biological systems. ROS are small oxygen-derived molecules with an important role in various biological processes (physiological or pathological). If under physiological conditions some processes are beneficial and necessary for life, under pathophysiological conditions they are noxious, harmful. NADPH oxidases are present in phagocytes and in a wide variety of nonphagocytic cells. The enzyme generates superoxide by transferring electrons from NADPH inside the cell across the membrane and coupling them to molecular oxygen to produce superoxide anion, a reactive free-radical. Structurally, NADPH oxidase is a multicomponent enzyme which includes two integral membrane proteins, glycoprotein gp9 1 Phox and adaptor protein p22(phox), which together form the heterodimeric flavocytochrome b558 that constitutes the core of the enzyme. During the resting state, the multidomain regulatory subunits p40P(phox), p47(phox), p67(Phox) are located in the cytosol organized as a complex. The activation of phagocytic NADPH oxidase occurs through a complex series of protein interactions.

THE PATIENT-DOCTOR-PSYCHOLOGIST TRIANGLE IN A CASE Of SEVERE IMUNOSUPRESSION IN THE HIV INFECTION.

In the last two years the Romanian adult population infected with the human immunodeficiency virus (HIV) has increased due to sexual transmission, both heterosexual and homosexual. The case presented is that of a 33 year-old man, admitted to the Infectious Diseases Hospital in Iasi with acute respiratory failure and a confirmation of Kaposi's sarcoma. Tests later proved positive for HIV, the patient being included in the stage AIDS C3 (acute immunodeficiency syndrome). The respiratory failure was suspected to be caused by Pneumocystis carinii and cotrimoxazol therapy, oxygen therapy and anti-retroviral therapy were established. He was also referred to the oncology hospital for treatment of Kaposi's sarcoma. The patient's adherence to therapy was influenced by a strong doctor-patient relationship, as well as by psychological counseling and support. Creating a functional doctor-patient-psychologist team is key throughout the HIV-positive patient's existence, for supporting long term adherence to therapy and acceptance of the diagnosis. This case highlights the need for a strong psychosocial compartment in every medical center that deals with HIV-infected individuals.

TB or not TB in HIV infection.

The progression of tuberculosis (TB) is significantly faster in patients with HIV infection. TB is also the main cause of death for HIV-infected individuals, resulting in fatality for 1 of 3 patients. We present the case of a 26-year-old male who arrived at the hospital having previously been diagnosed with HIV in 2014, but was not compliant to the ARV treatment prescribed. The patient presented with acute onset of fever, cough, hemoptysis and malaise. Investigations such as sputum samples and a lymph node biopsy revealed the presence of M. tuberculosis in optic microscopy, which led to a diagnosis of pulmonary and ganglionary TB. As one of the first opportunistic infections that occur in HIV-infected individuals, TB may be one of the earliest clues of an HIV infection. Current guidelines recommend that all individuals diagnosed with HIV should also undertake testing for TB infections.

Importance of Psychological Intervention in the Management of a Patient With Non-Hodgkin Lymphoma and Stage C3 AIDS Disease.

Long-term evolution of HIV because of noncompliance and nonadherence to antiretroviral therapy favors the occurrence of difficult to treat HIV-related malignancies. We present the case of a female patient in "the pediatric cohort" registered at the Iasi Regional HIV/AIDS Center since year 2000, now with stage C3 AIDS. In 2014, a Burkitt lymphoma was pathologically confirmed, and chemotherapy was initiated as recommended by the hematologist. The clinical course was characterized by multiple complications: hematologic and hepatic toxicities, opportunistic infections and depressive episodes. Highly active antiretroviral therapy associated with sustained psychological support resulted in stabilization of the patient's clinical course (lower HIV viral load and higher CD4 lymphocyte cell counts), anticancer therapy being better tolerated. Currently, patient's clinical-biological status is quasi-normal. The depressive episodes in this HIV-positive cancer patient undergoing chemotherapy contributed to her non-adherence and non-compliance to treatment, with serious consequences both on clinical and viroimmunological status. Therapeutic strategy in this patient with AIDS and Burkitt lymphoma raised management difficulties as both the drug interactions and cumulative adverse effects had to be considered. Multidisciplinary collaboration and especially psychological intervention are essential for creating a functional team, effective communication being key to achieving long-term adherence to treatment and diagnosis acceptance.

Lymphoma in an HIV-positive patient.

HIV/AIDS is considered to be revealing of oncological diseases, of which most frequent are lymphomas. The main causes for this type of disease are non-adherence and non-compliance to antiretroviral therapy (ART). We are hereby presenting a clinical case of lymphoma in an HIV-infected adult, with non-adherence for 30 months. In such a case the interdisciplinary collaboration with the hematologist was essential for the patient's survival.