Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update.

BACKGROUND: The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. AIM: To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. METHODS: This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. RESULTS: The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. CONCLUSION: This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Applications for oral research in microgravity - lessons learned from burning mouth syndrome and ageing studies.

The negative consequences of microgravity for the human body are central aspects of space travel that raise health problems. Altered functions of the same systems and treatment options are common points of spaceflight physiology, age-related diseases, and oral medicine. This work emphasizes the convergence of knowledge between pathophysiological changes brought on by aging, physiological reactions to microgravity exposure, and non-pharmacological and non-invasive treatment methods that can be used in spaceflight. Sarcopenia, peripheral nerves alterations, neuromotor plaque in the masticatory muscles, lingual, labial, and buccal weakness, nociplastic pain in oral mucosal diseases, and microgravity, as well as soft tissue changes and pathologies related to chewing and swallowing, corticomotor neuroplasticity of tongue, and swallowing biomechanics, are of particular interest to us. Neurologic disease and other pathologies such as recovery from post-stroke dysphagia, nociplastic pain in glossodynia, sleep bruxism, and obstructive sleep apnea have been studied and, in some cases, successfully treated with non-invasive direct and transcranial magnetic stimulation (TMS) methods in recent decades. An interdisciplinary team from medical specialties, engineering, and biophysics propose an exploratory study based on the parallelism of ageing and space physiology, along with experiment scenarios considering TMS and non-invasive direct methods.

A pilot sentinel surveillance system to monitor treatment and treatment outcomes of chronic hepatitis B and C infections in clinical centres in three European countries, 2019.

BackgroundThe World Health Organization European Action Plan 2020 targets for the elimination of viral hepatitis are that > 75% of eligible individuals with chronic hepatitis B (HBV) or hepatitis C (HCV) are treated, of whom > 90% achieve viral suppression.AimTo report the results from a pilot sentinel surveillance to monitor chronic HBV and HCV treatment uptake and outcomes in 2019.MethodsWe undertook retrospective enhanced data collection on patients with a confirmed chronic HBV or HCV infection presenting at one of seven clinics in three countries (Croatia, Romania and Spain) for the first time between 1 January 2019 and 30 June 2019. Clinical records were reviewed from date of first attendance to 31 December 2019 and data on sociodemographics, clinical history, laboratory results, treatment and treatment outcomes were collected. Treatment eligibility, uptake and case outcome were assessed.ResultsOf 229 individuals with chronic HBV infection, treatment status was reported for 203 (89%). Of the 80 individuals reported as eligible for treatment, 51% (41/80) were treated of whom 89% (33/37) had achieved viral suppression. Of 240 individuals with chronic HCV infection, treatment status was reported for 231 (96%). Of 231 eligible individuals, 77% (179/231) were treated, the majority of whom had received direct acting antivirals (99%, 174/176) and had achieved sustained virological response (98%, 165/169).ConclusionTreatment targets for global elimination were missed for HBV but not for HCV. A wider European implementation of sentinel surveillance with a representative sample of sites could help monitor progress towards achieving hepatitis control targets.

Assessment of the Humoral Immune Response Following COVID-19 Vaccination in Healthcare Workers: A One Year Longitudinal Study.

The continuous variability of SARS-CoV-2 and the rapid waning of specific antibodies threatens the efficacy of COVID-19 vaccines. We aimed to evaluate antibody kinetics one year after SARS-CoV-2 vaccination with an mRNA vaccine in healthcare workers (HCW), with or without a booster. A marked decline in anti-Spike(S)/Receptor Binding Domain (RBD) antibody levels was registered during the first eight months post-vaccination, followed by a transitory increase after the booster. At three months post-booster an increased antibody level was maintained only in HCW vaccinated after a prior infection, who also developed a higher and long-lasting level of anti-S IgA antibodies. Still, IgG anti-nucleocapsid (NCP) fades five months post-SARS-CoV-2 infection. Despite the decline in antibodies one-year post-vaccination, 68.2% of HCW preserved the neutralization capacity against the ancestral variant, with a decrease of only 17.08% in the neutralizing capacity against the Omicron variant. Nevertheless, breakthrough infections were present in 6.65% of all participants, without any correlation with the previous level of anti-S/RBD IgG. Protection against the ancestral and Omicron variants is maintained at least three months after a booster in HCW, possibly reflecting a continuous antigenic stimulation in the professional setting.

How and why do we screen for colorectal cancer?

After almost 50 years of data analysis, screening for colorectal cancer has proven to be an effective tool in reducing colorectal cancer mortality. However, implementing the optimal strategy represents a challenge for many healthcare facilities around the world. There is much discussion regarding how screening should be done, the optimal tools that should be used, and the proper timing for screening procedures. Another essential step is to maintain the adherence of patients to screening programs. Also, the recommendation for lowering the age to initiate screening is in progress, as there is an increase in colorectal incidence in people born after 1970.

Musculoskeletal adverse reactions after immunotherapy for cancer: A case series.

Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020. The oncologist, who identified the occurrence of rheumatic toxicities after the treatment with ICIs, evaluated the patients. Only oncological patients with rheumatic manifestations after the start of immunotherapy were included. Toxicity grading was performed by both the oncologist and the rheumatologist, on a scale from 1 to 5 (1, mild; 2, moderate; 3, severe; 4, life-threatening; 5, death related to toxicity). The results showed that rheumatoid factor, which was sampled in each patient, was negative in all cases. Patients were treated with nonsteroidal anti-inflammatory drugs or prednisone depending on the severity of the adverse events. The results varied with the severity of the adverse events. In conclusion, as the number of patients treated with ICIs increases, so will the number of patients presenting with immune-related adverse events (irAEs). The collaboration between oncologists and rheumatologists should be intimate to provide optimal treatment to patients. Musculoskeletal manifestations secondary to ICIs are slightly different from other rheumatologically conditions making diagnosis, treatment and monitoring difficult. Thus, irAEs are new and challenging for oncologists, thus understanding of the pathogenesis and clinical characteristics must be improved for better treatment guidelines.

Breast cancer mortality gaps in Romanian women compared to the EU after 10 years of accession: Is breast cancer screening a priority for action in Romania? (Review of the Statistics).

Breast cancer remains the most common cause of morbidity and mortality by cancer in females worldwide, even though it is largely preventable through population screening. Despite notable progress in the last years in the EU, breast cancer screening programs still maintain wide variations among countries and socio-economic groups. This statistical review aimed to investigate the breast cancer-related health gaps in Romanian women compared to the average EU female population after 10 years of accession (2007-2016). We evaluated breast cancer-related deaths, age-standardized mortality rates and contribution of breast cancer to life expectancy. Trends and percentage changes were compared between Romania and EU-27 for breast cancer, all cancer and all causes of mortality. We found a higher increase of breast cancer deaths in Romania, an increasing trend of mortality (opposite to EU) and a contribution to life expectancy at birth that increased gradually from 0.45 to 0 48 years. All these health gaps compared to EU are aggravated by the fact that no population screening for breast cancer is organized in the country. The opportunities for organizing such a program are consistent, but they should be increased in the future, in order to control the health gap between Romania and EU.

Cervical Cancer Mortality in Romania: Trends, Regional and Rural-Urban Inequalities, and Policy Implications.

Background and Objectives: Despite being largely preventable, cervical cancer mortality still remains an important public health problem globally, in Europe, and in Romania. The European Union member states are urged to implement systematic, population-based screenings for cervical cancer, but the programs developed by the countries remain very heterogeneous. This study aimed to investigate the differences in cervix cancer mortality between Romania and EU and within Romania over the last two decades and to reveal the major sources of inequalities and the policy implications. Materials and Methods: We analyzed the number of deaths and the mortality rates by cervical cancer, standardized using the direct method, over two decades (2001-2016 for the EU, and 2001-2019 for the national and sub-national analyses). Trends, mortality reduction over the years, and mortality differences at the beginning and end of the time interval have been calculated for the EU and Romania, at national and sub-national levels (rural-urban and regions). Results: Our results revealed differences in cervical cancer mortality between Romania and EU and within Romania (among regions and rural-urban areas). These differences used to be very high in the past and are still persisting. Conclusions: The country should revisit its national cervical cancer screening program, which has been implemented for many years, but with a very limited participation rate. Due to the similar problems existing in Central-Eastern Europe, targeted support from the EU for the members from this geographical area could contribute to the minimization of differences in cervical cancer mortality among the EU members.

Efficacy and Safety of Ledispavir/Sofosbuvir with or without Ribavirin in patients with Decompensated Liver Cirrhosis and Hepatitis C Infection: a Cohort Study.

BACKGROUND AND AIMS: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). METHODS: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. RESULTS: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). CONCLUSIONS: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

Modeling the Puzzle of Hepatitis C Epidemiology in Romania: A Pathway to Control.

BACKGROUND AND AIMS: To combat hepatitis C virus (HCV) and achieve its elimination by 2030, the emphasis should be on public health policies. In this study, we investigated the dynamics of epidemiology of HCV in Romanian risk groups that are characterized by higher occurrence densities with the aid of The Let's End HepC (LEHC) project. METHODS: The LEHC project addressed the modelling of HCV epidemiology, being applied in several countries, one of which is Romania. The model comprised an integrated solution of public health policies focused on the disease, using Adaptive Conjoint Analysis and Markov chains systems. This tool allowed the quantitative evaluation of public health policies' impact, for every year until 2030, in five population groups: people who inject drugs (PWID), prisoners, individuals who have received blood products, children at risk for vertical transmission, and the remnant population. RESULTS: It appears that Romania was already making great efforts in the context of public policies, allowing the achievement of HCV elimination by 2028 if current policies were maintained. Through additional work and greater efforts in further implementing public policies, the LEHC model estimated the possibility of anticipating this outcome to 2026. CONCLUSION: The LEHC model estimated an anticipation of the HCV elimination year in Romania to be 2026 if the twenty-four health policies in the study are fully implemented and consistently maintained over the years.

Correlation of Biomarkers with Endoscopic Score: Ulcerative Colitis Endoscopic Index of Severity (UCEIS) in Patients with Ulcerative Colitis in Remission.

Background: Ulcerative colitis is a disease with an unpredictable evolution, often highlighted endoscopically, that is associated with persistent inflammation affecting the patient's quality of life. An attempt was made to discover surrogate markers to evaluate the endoscopic remission of the disease in order to increase the patient's quality of life and also their adherence to the treatment and monitoring plan. One such marker is fecal calprotectin (FC). Aims: To confirm the correlation between biomarkers and endoscopic disease activity and to define the optimal cut off value to detect clinical and endoscopic remission in a center of Romania. Methods: This was a prospective study that included 59 patients diagnosed with ulcerative colitis at the Department of Internal Medicine III, University Emergency Hospital of Bucharest. Patients had fecal calprotectin measurements and colonoscopy/rectosigmoidoscopy performed during baseline, 6 and 12 months. For endoscopic activity the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) was used. Results: During the study, relapses have occurred in 35.6% of patients, the median age was 47 years (21-77). During the study, the FC measurement was significantly increased at 3 months (median, range µg/g; 715, 14-4000) and at 6 months (median, range µg/g; 650, 4.5-3000) (p ≤ 0.05). Another inflammatory biomarker studied was CRP, which showed increased values at 3 months (median, range, mg/dL; 1.86, 0.14-58.9), at 6 months (median, range, mg/dL; 2.36, 0.12-45.8) and at 9 months (median, range, mg/dl; 2, 0.12-25.9) compared to the baseline (p = 0.01). Patients with recurrence of the disease also associated an increase in the values of clinical evaluation scores (SCCAI; p = 0.00001), but also endoscopic (UCEIS; p = 0.0006) Conclusion: A relapse is associated independently with younger age, the extension of the disease (E2-E3), increased FC level, C reactive protein, hemoglobin concentration, SCCAI index and UCEIS score.

Efficacy and safety of APT036 versus simethicone in the treatment of functional bloating: a multicentre, randomised, double-blind, parallel group, clinical study.

BACKGROUND: Bloating is a common symptom reported by around 16% to 31% of the general population. Functional bloating is diagnosed in patients with recurrent symptoms of bloating who do not meet the diagnostic criteria of irritable bowel syndrome or other functional gastrointestinal disorders. METHODS: This double-blind, multicentre, randomised study compared the safety and efficacy of APT036 (xyloglucan plus tyndallized Lactobacillus reuteri and Bifidobacterium brevis; Aprotecol®) and simethicone in treating functional bloating in adults. APT036 or simethicone were administered orally (3 times/day) for 20 consecutive days, with evaluations at baseline, and on Days 2, 10, 20 (end of treatment) and 30 (follow-up visit). The main outcome measure was safety. Efficacy was assessed at each visit by patient-reported symptom severity (Likert scale) and abdominal girth measurement. A hydrogen breath test was performed at baseline and Day 20. RESULTS: Both APT036 (n=54) and simethicone (n=54) were well tolerated by study subjects; no adverse effects were reported with either treatment. Compared with simethicone, APT036 significantly reduced abdominal distension (P=0.008) and flatulence (P=0.010) from baseline to Day 30. The baseline hydrogen breath test confirmed the presence of small intestinal bacterial overgrowth (SIBO) in all subjects. At Day 20, mean hydrogen gas elevation was below the threshold for a diagnosis of SIBO (<12 ppm above basal on glucose administration) in both study arms. CONCLUSIONS: Both APT036 and simethicone had good safety profiles but APT036 was superior to simethicone in relieving symptoms of functional bloating.

New Definition Criteria of Myocardial Dysfunction in Patients with Liver Cirrhosis: A Speckle Tracking and Tissue Doppler Imaging Study.

There are no clear recommendations regarding cirrhotic cardiomyopathy (CC) evaluation in patients with pre-transplant liver cirrhosis. The roles of new methods, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in the diagnosis and prognosis of cirrhotic cardiomyopathy remain controversial. We investigated the utility of TDI/STE parameters in cirrhotic cardiomyopathy diagnosis and also in predicting mortality in patients with liver cirrhosis. Left/right ventricular function was studied using conventional TDI (velocities) and STE (strain/strain rate). We assessed left ventricular diastolic dysfunction, graded into four new classes (I/Ia/II/III). Serum NTproBNP (N-terminal prohormone of brain natriuretic peptide), troponin I, ß-crosslaps, QTc interval, arterial compliance and endothelial function were measured. Liver-specific scores (Child-Pugh, MELD, MELDNa) were computed. There was a 1-y follow-up visit to determine mortality. We observed resting biventricular diastolic myocardial dysfunction, not presently included in the definition of cirrhotic cardiomyopathy. We provided an improved characterization of cardiac dysfunction in patients with liver cirrhosis. This might change the current definition. However, the utility of STE/TDI parameters in predicting long-term mortality in patients with liver cirrhosis remains controversial.

Real-world efficacy and safety of ombitasvir, paritaprevir/r+dasabuvir+ribavirin in genotype 1b patients with hepatitis C virus cirrhosis.

BACKGROUND: Direct antiviral agents (DAA) showed very good results in terms of efficacy and safety in clinical trials, but real-life data are still needed in order to confirm this profile. MATERIAL AND METHODS: In Romania, through a nationwide government-funded programme in 2015-2016, approx.5800 patients with virus C cirrhosis received fully reimbursed DAA therapy with OBV/PTV/r+DSV+RBV for 12 weeks. We analysed a national prospective cohort enrolling the first 2070 patients, all with genotype 1b. The only key inclusion criteria was advanced fibrosis (Metavir stage F4) confirmed by Fibromax testing (or liver biopsy/Fibroscan). Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). RESULTS: Forty patients stopped the treatment because of hepatic decompensation (1.9%), 21 stopped because of other adverse events and one was lost to follow-up. This cohort was 51% females, mean age 60 years (25÷82), 67% pretreated, 70% associated NASH, 67% with severe necro-inflammation (severity score 3-Fibromax), 37% with comorbidities, 10.4% with Child Pugh A6, 0.5% B7. The median MELD score was 8.09 (6 ÷ 22). SVR by intention-to-treat was reported in 1999/2070(96.6%), 55/2070 failed to respond. Liver decompensation was statistically associated in multivariate analysis with platelets< 105 /mm3 (P = .03), increased total bilirubin (P < .001), prolonged INR (P = .02), and albumin<3.5 g/dL (P = .03). CONCLUSIONS: OBV/PTV/r+DSV+RBV proved to be highly efficient in our population of cirrhotics with a 96.6% SVR. Serious adverse events related to therapy were reported in 61/2070(2.9%), most of them liver decompensation (1.9%), related to hepatic dysfunction, and lower platelet count.

ANEMIA IN INFLAMMATORY BOWEL DISEASE MORE THAN AN EXTRAINTESTINAL COMPLICATION.

The most common hematologic complication of inflammatory bowel disease (IBD)--ulcerative colitis and Crohn's Disease is anemia. Anemia in patients with IBD may be a result of iron, vitamin B12 or folate deficiency; anemia of chronic disease and hemolytic anemia are other causes in these patients. Factors contributing to the development of anemia include chronic gastrointestinal blood loss, vitamin B12 malabsorption secondary to terminal ileitis, folate deficiency as a result of sulfasalazine therapy. Approximately 30% of patients with IBD have hemoglobin levels below 12 g/dl. The risk of developing anemia relates to disease activity, given that blood loss and inflammatory anemia are triggered by intestinal inflammation. In the management strategy of IBD patients with anemia it is important to distinguish between the different types of anemia in order to decide an appropriate manner of treatment.

Biocompatible hydrodispersible magnetite nanoparticles used as antibiotic drug carriers.

Here we report a newly synthesized vectorizing nanosystem, based on hydrodispersible magnetite nanoparticles (HMNPs) with an average size less than 10 nm, obtained by precipitation of Fe(II) and Fe(III) in basic solution of p-aminobenzoic acid (PABA), characterized by high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), differential thermal analysis coupled with thermogravimetric analysis (DTA-TGA) and bioevaluated for cytotoxicity and antibiotic delivery in active forms. The obtained data demonstrate that HMNPs can be used as an efficient drug delivery system, for clinically relevant antimicrobial drugs. HMNPs antimicrobial activity depended on the loaded drug structure and the tested microbial strain, being more efficient against Pseudomonas aeruginosa, comparing with the Escherichia coli strain. The novel HMNPs demonstrated an acceptable biocompatibility level, being thus a very good candidate for biomedical applications, such as drug delivery or targeting.

Tuberculosis of the oral cavity.

Tuberculosis (TB) of the tongue is not a common finding diagnosis, even if consider endemic areas. Tuberculosis of the tongue sometimes can mimic lingual neoplasm. Oral tuberculosis is rarely primary as mechanism, and frequently secondary to pulmonary tuberculosis. There are many suspect lesions that can be classified as tuberculosis, such as tumor mass, ulcerative lesion or fissure. It is very important for diagnosis to perform histopathological examination of the biopsy. We present here the case of a 74-year-old man who developed lingual tuberculosis with a tumor aspect concomitant with pulmonary tuberculosis. Histopathological and immunohistochemical examinations established the diagnosis of lingual tuberculosis.

Thoracic endometriosis with a long delay in diagnosis.

This paper describes a case of thoracic endometriosis in 36-year-old woman with a long delay in diagnosis. At the admission in the hospital, the patient had a medical history of persistent dysmenorrhea since the age of 13, infertility and an episode of total right pneumothorax two months ago successfully resolved by minimum pleurotomy of the right hemitorax. She came with moderate pain on right hemithorax and dyspnea, which occurred on the first day of menstruation but she did not have any other respiratory symptoms such as hemoptysis, cough. Radiological imaging (chest radiography and computer tomography) at the time of admission confirmed recurrence of the right pneumothorax. She underwent surgical treatment of the right pneumothorax using a single-port video-assisted approach. Intraoperative macroscopic lesions were found catamenial pneumothorax characteristic diagnosis and biopsy material taken (parietal pleura) for histopathology. Immuno-histochemical tests confirmed the diagnosis of thoracic endometriosis. The gonadotropin-releasing hormone analogue was received by the patient early after surgery and there was no clinical or radiological recurrence at a four months follow-up.

Metallic-based micro and nanostructures with antimicrobial activity.

The spectacular progress of research in the nanotechnology field led to the achievement of important knowledge of materials at the atomic and molecular scale and the extent of the use of nanoparticles in the design of medical products, ecological processes, cosmetics and other biotechnological applications. One of the current focuses of the medical applications of nanotechnology is the development of new strategies to inhibit the activity of different microorganisms. The purpose of this review was to present the antimicrobial activity of metal cations in micro- and nanoparticulate forms and the dependence of this biological activity on shape, size and physico-chemical conditions.