Non-Invasive Prediction Scores for Hepatitis B Virus- and Hepatitis D Virus-Infected Patients-A Cohort from the North-Eastern Part of Romania.

Approximately 62-72 million people are infected worldwide with HDV. Patients with chronic hepatitis D (CHD) have a higher risk of developing cirrhosis or hepatocellular carcinoma (HCC) and an increased mortality rate compared to those with chronic hepatitis B (CHB). The stage of liver fibrosis or the risk of developing HCC can also be estimated by non-invasive scores, which are cost effective, easier to apply, and reproducible. In this study, we aimed to evaluate the predictive value of four non-invasive scores (FIB-4, APRI, AST/ALT ratio, and aMAP) in assessing severe fibrosis/cirrhosis and the presence of HCC in patients with HBV/HDV superinfection, as compared with HBV mono-infection. Our 8-year retrospective analysis revealed that HDV-infected patients had a 2-3 times higher risk of developing cirrhosis and HCC than HBV-mono-infected subjects. High AST and ALT baseline levels qualified as independent predictors for cirrhosis development in both groups. The following fibrosis scores, FIB-4, APRI score, and AAR, were significantly increased when cirrhosis was present at baseline and showed a good prediction for developing cirrhosis in the CHD group. The aMAP score, a risk predictor for HCC, showed significantly higher values in patients with HCC in both groups. Nonetheless, non-invasive scores should always be considered for monitoring patients with CHB and CHD, but only when associated with other diagnosis methods.

The Clinical Utility of Circulating HPV DNA Biomarker in Oropharyngeal, Cervical, Anal, and Skin HPV-Related Cancers: A Review.

Human papillomavirus (HPV) is recognized as being related to a wide variety of known cancers: cervical, oropharyngeal, anal, vaginal, penile, and skin. For some of these cancers, rigorous algorithms for screening, therapeutical interventions, and follow-up procedures have been established. Vaccination using the nonvalent anti-HPV vaccine, which prevents infection regarding the most frequently involved high-risk HPV types (16, 18, 31, 33, 45, 52, and 58) and low-risk HPV types (6 and 11), has also extensively prevented, controlled, and even eradicated HPV infections. Still, even with all of these multidisciplinary interventions, the burden of HPV cancers is still high worldwide. The circulating DNA of HPV-induced cancers is thought to be an adequate biomarker for optimizing the control of these virus-related cancers. We analyzed the literature published in the last 5 years regarding ctDNA and four of the above-mentioned cancers. The most frequently used assay for ctDNA detection was the droplet digital PCR assay, used for the management of therapy in the late stages of cancer. ctDNA could not be used for early detection in any of the studied cancers. The OPSCCs were the most frequent cancers analyzed via ctDNA assays. Larger, properly designed cohort studies might establish the clinical utility of this biomarker.

The Influence of Oncogenic Viruses in Renal Carcinogenesis: Pros and Cons.

Viral infections are major contributors to the global cancer burden. Recent advances have revealed that known oncogenic viruses promote carcinogenesis through shared host cell targets and pathways. The aim of this review is to point out the connection between several oncogenic viruses from the Polyomaviridae, Herpesviridae and Flaviviridae families and renal carcinogenesis, highlighting their involvement in the carcinogenic mechanism. We performed a systematic search of the PubMed and EMBASE databases, which was carried out for all the published studies on RCC in the last 10 years, using the following search algorithm: renal cell carcinoma (RCC) and urothelial carcinoma, and oncogenic viruses (BKPyV, EBV, HCV, HPV and Kaposi Sarcoma Virus), RCC and biomarkers, immunohistochemistry (IHC). Our analysis included studies that were published in English from the 1st of January 2012 to the 1st of May 2022 and that described and analyzed the assays used for the detection of oncogenic viruses in RCC and urothelial carcinoma. The virus most frequently associated with RCC was BKPyV. This review of the literature will help to understand the pathogenic mechanism of the main type of renal malignancy and whether the viral etiology can be confirmed, at a minimum, as a co-factor. In consequence, these data can contribute to the development of new therapeutic strategies. A virus-induced tumor could be efficiently prevented by vaccination or treatment with oncolytic viral therapy and/or by targeted therapy.

Diagnostics of HNSCC Patients: An Analysis of Cell Lines and Patient-Derived Xenograft Models for Personalized Therapeutical Medicine.

Head and neck squamous cell carcinomas (HNSCC) are very frequent worldwide, and smoking and chronic alcohol use are recognized as the main risk factors. For oropharyngeal cancers, HPV 16 infection is known to be a risk factor as well. By employing next-generation sequencing, both HPV-positive and negative HNSCC patients were detected as positive for PI3K mutation, which was considered an optimal molecular target. We analyzed scientific literature published in the last 5 years regarding the newly available diagnostic platform for targeted therapy of HNSCC HPV+/-, using HNSCC-derived cell lines cultures and HNSCC pdx (patient-derived xenografts). The research results are promising and require optimal implementation in the management of HNSCC patients.

Merkel Cell Polyoma Virus and Cutaneous Human Papillomavirus Types in Skin Cancers: Optimal Detection Assays, Pathogenic Mechanisms, and Therapeutic Vaccination.

Oncogenic viruses are recognized to be involved in some cancers, based on very well-established criteria of carcinogenicity. For cervical cancer and liver cancer, the responsible viruses are well-known (e.g., HPV, HBV); in the case of skin cancer, there are still many studies which are trying to identify the possible viral etiologic agents as principal co-factors in the oncogenic process. We analysed scientific literature published in the last 5 years regarding mechanisms of carcinogenicity, methods of detection, available targeted therapy, and vaccination for Merkel cell polyomavirus, and beta human papillomavirus types, in relation to skin cancer. This review is targeted at presenting the recent findings which support the involvement of these viruses in the development of some types of skin cancers. In order to optimize the management of skin cancer, a health condition of very high importance, it would be ideal that the screening of skin cancer for these two analysed viruses (MCPyV and beta HPV types) to be implemented in each region's/country's cancer centres' molecular detection diagnostic platforms, with multiplex viral capability, optimal sensitivity, and specificity; clinically validated, and if possible, at acceptable costs. For confirmatory diagnosis of skin cancer, another method should be used, with a different principle, such as immunohistochemistry, with specific antibodies for each virus.

Subgingival Periopathogens Assessment and Clinical Periodontal Evaluation of Gastric Cancer Patients-A Cross Sectional Pilot Study.

Oral microbiota have shown a higher bacterial diversity in patients with cancers of the digestive tract, with higher levels of periopathogens. Recent studies have shown that Fusobacterium links to gastro-intestinal neoplastic tissue and accelerates its progression, as well as worsening patient outcome. The present pilot study was carried out between February and December 2020 to evaluate the possible association between the abundance of some periopathogens (Fusobacterium nucleatum, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia) in subgingival plaque and periodontal status with characteristics of gastric cancer. The study was performed on a sample of 24 patients with gastric cancer from the 1st Department of Surgery and Department of Gastroenterology within the Clinical County Hospital of Emergency of Craiova, Romania. The patients' oral cavity was examined, gingival crevicular samples were collected, and signs of periodontal disease were recorded. On the histopathological exam, the differentiation grade and size of the tumour were registered. Our results showed that, from the periopathogens studied, the most abundant bacteria were F. nucleatum followed by T. forsythia in all groups. In our present study, the strong correlation between tumour dimension and all periodontal parameters but also between tumour dimension and F. nucleatum could suggest a positive association between periodontal disease, tumoral growth and periopathogens implication in this process.

Indwelling Device-Associated Biofilms in Critically Ill Cancer Patients-Study Protocol.

Health care-associated infections are a leading cause of inpatient complications. Rapid pathogen detection/identification is a major challenge in sepsis management that highly influences the successful outcome. The current standard of microorganism identification relies on bacterial growth in culture, which has several limitations. Gene sequencing research has developed culture-independent techniques for microorganism identification, with the aim to improve etiological diagnosis and, therefore, to change sepsis outcome. A prospective, observational, non-interventional, single-center study was designed that assesses biofilm-associated pathogens in a specific subpopulation of septic critically ill cancer patients. Indwelling device samples will be collected in septic patients at the moment of the removal of the arterial catheter, central venous catheter, endotracheal tube and urinary catheter. Concomitantly, clinical data regarding 4 sites (nasal, pharyngeal, rectal and skin) of pathogen colonization at the time of hospital/intensive care admission will be collected. The present study aims to offer new insights into biofilm-associated infections and to evaluate the infection caused by catheter-specific and patient-specific biofilm-associated pathogens in association with the extent of colonization. The analysis relies on the two following detection/identification techniques: standard microbiological method and next generation sequencing (NGS). Retrospectively, the study will estimate the clinical value of the NGS-based detection and its virtual potential in changing patient management and outcome, notably in the subjects with missing sepsis source or lack of response to anti-infective treatment.

Role of mucosal high-risk human papillomavirus types in head and neck cancers in Romania.

BACKGROUND: Limited information is available about the involvement of human papillomavirus (HPV) in head and neck squamous cell carcinomas (HNSCCs) in Romanian patients. OBJECTIVE: To evaluate the HPV-attributable fraction in HNSCCs collected in Northeastern Romania. MATERIALS AND METHODS: In total, 189 formalin-fixed paraffin-embedded tissue samples (99 oral cavity tumors, 28 oropharynx, 48 pharynx, and 14 larynx/hypopharynx) were analyzed for HPV DNA and RNA using Luminex-based assays, and for overexpression of p16INK4a (p16) by immunohistochemistry. RESULTS: Of the 189 cases, 23 (12.2%) were HPV DNA-positive, comprising half of the oropharyngeal cases (14/28, 50.0%) and 9/161 (5.6%) of the non-oropharyngeal cases. HPV16 was the most prevalent HPV type (20/23, 86.9%), followed by HPV18 (5/23, 21.7%) and HPV39 (1/23, 4.3%). Only two (2/189, 1.1%) HNSCC cases were HPV-driven, i.e. positive for both HPV DNA and RNA. CONCLUSION: A very small subset of HNSCC cases within this cohort from Northeastern Romania appeared to be HPV-driven.

The Need for Cervical Cancer Control in HIV-Positive and HIV-Negative Women from Romania by Primary Prevention and by Early Detection Using Clinically Validated HPV/DNA Tests.

BACKGROUND: In Romania, a country with no organized national surveillance program regarding cervical cancer, the early diagnosis of HPV (Human Papilloma Virus) infections is a major requirement, especially in HIV-infected women. The objective of this study was to determine the HPV prevalence and type distribution in young HIV-positive women and to assess the difference in the risk factors for developing cervical cancer compared to those of HIV-negative women. METHOD: We conducted one cross-sectional cohort study from June 2013-September 2014, including 1,032 women: 992 HIV- women who were 36.5 years old (limits: 17 ÷ 84) and 40 HIV + women who were 22.9 years old (limits: 17 ÷ 30) with iatrogenic HIV infected. We detected HPV types with the Linear Array HPV Genotyping test (Roche, Romania). RESULTS: DNA/HPV was detected in 18/40 (45%) of the HIV+ patients and in 350/992 (35.2%) of the HIV- patients (OR = 1.5, 95%CI 0.76÷2.96). After age adjustment, the overall HPV prevalence was 51.6% in HIV+ versus 63.2% in HIV- women aged under 25, and 22.2% in HPV+ versus 47.2% in HIV- women aged 25-34. We detect HIV being a risk factor for acquiring multiple HPV type infections (OR = 2.30, 95% CI 0.88÷5.97). The eight most common HPV types (high-risk, and low-risk) for women below age 30, HIV+ / - were: HPV 16, 18, 31, 51, 58, 68, and 6 and 82 respectively. To assess the risk factors of HIV-positive women for acquiring HPV infection, we analyzed the CD4/µL, ARN/HIV copies/µL, the age group, the number of sexual partners, smoking, and the type of HPV infection (single versus multiple infections). We found that the number of sexual partners and smoking are statistically significant risk factors. CONCLUSION: Even though there are no significant differences regarding the prevalence of HPV infection in HIV + versus HIV - patients, multiple infections were more frequent in the first group. In our study group young HIV-infected patients under HAART therapy, high number of sexual partners (more than 3) and smoking were detected to be risk factors. Future organized screening for HPV infection using sensitive and specific methods are necessary at the national level in Romania.

DETECTION OF HUMAN PAPILLOMA VIRUS IN HEAD AND NECK SQUAMOUS CELL CARCINOMAS: A LITERATURE REVIEW.

Human papilloma viruses (HPV) are the most common sexually transmitted viruses. There is mounting evidence that incriminates HPV as a risk factor for malignant transformation of oropharyngeal epithelium. In 2011 the International Research Agency of Cancer and National Cancer Institute (USA) declared HPV-16 as an independent risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Leaders in the field of HPV research admit that this subtype of head and neck cancer is a sexually transmitted entity and its global incidence is on the rise. In the 1980s, clinicians observed a new group of patients with head and neck squamous cell carcinoma (HNSCC) independent of tobacco smoking or alcohol use. The new HNSCC patient is a middle-aged man, non-smoker, non-drinker with higher social status and the suspected risk factors for HNSCC being related to sexual practices (oral sex, multiple sexual partners, unprotected sex and drug use). Routine HPV testing of HNSCC patients is seriously considered as HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical and pathologic entity that has a markedly better prognosis than HPV-negative oropharyngeal cancers. The current treatment protocols for OPSCC include radiation, chemotherapy and surgery alone or in combination, involving high toxicity levels. Future therapeutic concepts for OPSCC may be personalized in relation to HPV-status to avoid unnecessary toxicity. The current review summarizes the contemporary trends in the diagnosis of HPV-related head and neck cancers, presenting the advantages and disadvantages of the main methods.

Human papillomavirus 52 positive squamous cell carcinoma of the conjunctiva.

Human papillomavirus (HPV) infection is strongly associated with several human cancers; the most known genotypes involved being HPV 16 and HPV 18. We report the detection of HPV 52 in a sample taken from a 47-year-old patient with squamous cell carcinoma of the conjunctiva of the left eye. The method used for the detection of HPV was real time polymerase chain reaction. The evolution was favorable after surgical removal of the tumor and the patient was explained that long-term follow-up is essential to avoid recurrence.

ETIOLOGY AND RESISTANCE PROFILE OF ISOLATED STRAINS FROM SEVERE SYSTEMIC INFECTIONS IN PATIENTS WITH IMMUNODEPRESSION--EXPERIENCE OF THE IASI INFECTIOUS DISEASES HOSPITAL 2011-2014.

UNLABELLED: Microbial resistance is an increasingly serious threat to global public health and it is linked to patient's age, immune status, and also antibiotic overuse or misuse and repeated hospitalizations. The high incidence of infections caused by multidrug-resistant bacteria requires rethinking the first-line therapeutic schemes. AIM: Retrospective study of the etiologic and antibiotic resistance profile of the bacterial strains isolated from immunocompromised hosts diagnosed with severe systemic infections, aimed at gaining a better understanding of the potential infectious sources and optimizing the antibiotic therapy. MATERIAL AND METHODS: 178 cases of severe sepsis associated with immunosuppression (caused by diabetes, malignancies, liver cirrhosis, chronic alcohol abuse, kidney failure) were admitted to the "St. Parascheva" Infectious Diseases Hospital Iasi in the interval January 2011- December 2014. RESULTS: The mean age of the study patients was 61 years, most patients being female (53%) and living in urban areas (51%). The causal agents were: Escherichia coli (20.2%), Klebsiella pneumoniae (16.8%), Pseudomonas aeruginosa (14.6%), Methicillin-Sensitive Staphylococcus aureus (MSSA) (11.2%), Enterococcus spp. (10.1%), Methicillin-Resistant Staphylococcus aureus (MRSA) (8.9%), Proteus spp.(5%), Acinetobacter baumanii (5%), Streptococcus pyogenes (1.6%), Staphylococcus epidermidis (1.1%) and Citrobacter (0.5%). As to the resistance profile the following were found: 100% susceptibility of MRSA and Enterococcus species to vancomycin, as well as for the Enterococcus species; 27% of E. coli strains were resistant to beta-lactams and 20% of Klebsiella pneumoniae to carbapenems. Antibiotic therapy associated two or three drugs with an immediate result and a favorable outcome in 84.2% of the cases. CONCLUSIONS: The etiological agents implicated in the occurrence of severe sepsis in patients with acquired immunosuppression were Gram-positive bacteria (GPB) as well as Gram-negative bacteria (GNB) with moderate resistance to usual antibiotics. The infections caused by GNB were predominant in immunocompromised patients, but also in those with associated urinary and respiratory tract infections and chronic indwelling urinary catheters. In our severe sepsis patients Gram positive bacteria caused mainly skin and joint infections.

Epidemiological and pathological aspects of skin cancer in North East of Romania.

UNLABELLED: In the last years skin cancer has become the most frequent cancer in humans, with the majority made up of two tumors: malignant melanoma (MM) and non-melanoma skin cancer (NMSC). AIM: To provide for the first time in the North East region of Romania, descriptive epidemiological data of melanoma and non-melanoma skin cancers. MATERIAL AND METHODS: We undertook a retrospective study over a five year period on the most frequent forms of skin cancer, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and MM, which included a total number of 1231 patients, hospitalized and treated in the Plastic Surgery Department of "St. Spiridon" Emergency Clinical Hospital, Iasi from 2008 until 2012. Results: BCC was diagnosed in a total of 675 patients, representing 54.9%. SCC was found in 217 patients, representing 17.6% and melanoma was diagnosed in 119 cases, a percent of 9.7% of the total number. The predominance of cutaneous malignancies waried with age, major site distribution was face and neck for BCC and SCC and the trunk for MM. RESULTS: This article describes the most common forms of skin cancer in our region, BCC (almost 55%), SCC (17.6%), and less in number MM (near to 10%); these results are similar to those published abroad in the last years. CONCLUSIONS: Future more elaborate interventional studies are necessary to identify the main risk factors in order to design the best preventive methods and, according to the skin cancer trend to specify the needs for dermatology network in our country.

Epidemiological and laboratory features of chronic hepatitis B cases in the interval 2010-2013.

UNLABELLED: HBV virus infection is an important public health problem because of its huge transmission potential, and severe evolution to cirrhosis or liver cancer. AIM: Analysis of the epidemiological and laboratory features of chronic hepatitis B virus infection. MATERIAL AND METHODS: The patients with chronic hepatitis B admitted to the "Sf. Parascheva" University Hospital for Infectious Diseases in the interval: January 1st, 2010 - December 31st were analyzed. RESULTS: Patients age was 18 to 66 years with a prevalence of middle-aged males. Most patients came from urban areas. Alanine aminotransferase (ALAT) levels were elevated, without significant differences between HBeAg-positive and HBeAg-negative patients, the elevated ALAT levels being associated with the increased prevalence of fibrosis. HBeAg-positive patients had viral loads above the threshold of 2,000/l in 34 cases (89.5%), and below 2,000 IU/l in only 10.5% of cases, and the majority (88%) of HBeAg-negative patients presented high viral load levels. The prevalence of stage F2-F4 liver fibrosis was 63.4% in the HBeAg-negative patients with viremia > 25,000 IU/l compared to 55.2% in the HBeAg-positive patients. The correlation between the level of viral load and fibrosis shows that there are significant differences between viremia and the status of HBeAg-positive or negative patients. Increased viral load was correlated with increasing prevalence of fibrosis, significant in HBeAg-negative patients, and the increasing fibrosis prevalence was correlated with low viral load. CONCLUSIONS: The correlation between viral load and fibrosis shows that there are significant differences between viral load and the status of HBAg-positive or negative patients.

Epidemiological aspects of hydatidosis in children, in some areas of north-eastern Romania.

UNLABELLED: Hydatid cyst is a major public health problem in the pediatric population, both in terms of its frequency and of its endemic character in certain regions. The aim of the study was to present the incidence of hydatidosis in children who were hospitalized in pediatric clinics specialized in surgery of the Emergency Hospital for Children "St. Maria" from lasi. MATERIAL AND METHODS: Prospective study conducted in the interval 2008-2012 in a series of 194 children patients from Moldova, Romania. RESULTS: The peak incidence of the hydatid disease is located around the age of 11-14 years (33%) in male patients (55%) from rural areas (79%) and families with low socioeconomic level. The hepatic localization of the hydatid cyst (50.51%) among children was more common than pulmonary localization (16.49%). Liver and lung localization was found in 22.16% of cases. CONCLUSIONS: Hydatidosis remains a major health problem requiring drastic measures to limit the spread and transmission of the parasite in humans, primarily by reducing the number of stray dogs.

HPV prevalence and type distribution in women with or without cervical lesions in the Northeast region of Romania.

BACKGROUND: Cervical cancer is a major public health problem worldwide. While Romania has the highest incidence of cervical cancer in Europe, the prevalence of HPV has not been evaluated. We report the first data on HPV prevalence and type distribution in Northeast Romania. METHODS: HPV prevalence and genotype distribution was investigated in 514 consecutively women with or without cervical lesions in Northeast Romania. Genotyping was performed with Linear Array Genotyping/Roche kit. RESULTS: In our study group, 192/514 (37.4%) patients were positive for HPV (infected with single and with multiple HPV types). Most frequent types were: 16 (10.5%), 53 (5.44%), 51 (5.05%), 52 (4.08%) 18 (2.91%) and 31 (2.73%). CONCLUSIONS: Infection with high risk types of HPV is common in Northeast Romania. Enhanced and systematic screening for cervical cancer is needed. Our results call for the implementation of a National HPV vaccine program in Romania.

[Polyomavirus BK and its role in associated kidney transplantation pathology]. / Virusul polyoma bk s implicatiile acestuia în patologia asociata transplantului renal.

In the last three decades kidney transplantation became a therapeutic approach in Romania but, unfortunately, the increasing of kidney transplantation procedures is related to an increasing rate of associated pathology such as Polyomavirus BK Associated Nephropathy (BKVAN). Studies published recently emphasize that BKVAN is a consequence of different risks factors, particular viral pathogenesis, humoral and cellular immunity and high doses of immunosuppressive drugs used for a long time are the main conditions that influence the BKVAN's evolution. Since there is no specific and effective treatment, optimal medical management is to diagnose nephropathy in early stages, to stop viral replication, limiting tubular lesions and prevent progress toward destruction by decreasing doses of immunosuppressive agents.

[Enhanced molecular techniques for the diagnosis of human papillomavirus infections]. / Optimizarea unor tehnici de biologie moleculara pentru diagnosticul infectiilor cu virusuri papilloma umane.

OBJECTIVES: optimisation of Real Time PCR technique for quantifying oncogenic types 16 and 18 of Human Papilloma Viruses, genotyped through classic PCR, followed by hybridisation. MATERIAL AND METHOD: DNA/ HPV was purified with High Pure PCR Template Preparation kit (ROCHE DIAGNOSTICS), genotyping was performed with Linear Array HPV Genotyping (ROCHE DIAGNOSTICS) and PCR reaction was realized with ABI 9700 Gold Plate System. Absolute quantification of HPV 16 and 18 was performed with Path-HPV16/18 Real-time PCR detection kit for Human Papillomavirus, 2 x Precision Mastermix kits (PrimerDesign), and the instrument used was MX3000P STRATAGENE. RESULTS: I. HPV genotyping was optimised through testing of 12 cervical samples, collected from patients who have signed the informed consent approved by the local Bioethical Committee. Among the tested samples, 5 were negative for any HPV type, 3 patients had unique infections with oncogenic HPV type, and 2 patients had multiple infections, with oncogenic and non-oncogenic HPV types. Negative and positive controls were validated, identical as the internal control - beta globin gene. II. Absolute quantification for HPV 16 and 18 were performed on two samples tested by the previous method. The number of viral copies was determined using the standard curves procedure, whose parameters values were between the accepted limits. CONCLUSIONS: We fulfilled the quality criteria for both techniques: genotyping assay and viral load quantification by Real Time PCR. This allows us to start the study for monitoring persistent infections with HPV 16 and HPV 18.