The Spatial-Temporal Dimension of Oncological Prevalence and Mortality in Romania.

The objective of this study was to identify spatial disparities in the distribution of cancer hotspots within Romania. Additionally, the research aimed to track prevailing trends in cancer prevalence and mortality according to a cancer type. The study covered the timeframe between 2008 and 2017, examining all 3,181 territorial administrative units. The analysis of spatial distribution relied on two key parameters. The first parameter, persistence, measured the duration for which cancer prevalence exceeded the 75th percentile threshold. Cancer prevalence refers to the total number of individuals in a population who have been diagnosed with cancer at a specific time point, including both newly diagnosed cases (occurrence) and existing cases. The second parameter, the time continuity of persistence, calculated the consecutive months during which cancer prevalence consistently surpassed the 75th percentile threshold. Notably, persistence of elevated values was also evident in lowland regions, devoid of any discernible direct connection to environmental conditions. In conclusion, this work bears substantial relevance to regional health policies, by aiding in the formulation of prevention strategies, while also fostering a deeper comprehension of the socioeconomic and environmental factors contributing to cancer.

RARE DOSAGE ABNORMALITIES - COPY NUMBER VARIATIONS FLANKING THE SHOX GENE.

Background: Molecular defects in the SHOX gene including deletions, duplications or pathogenic point mutations are responsible for well-known pathologies involving short stature as a clinical manifestation: Léri-Weill dyschondrosteosis, Langer mesomelic dysplasia, Turner syndrome or idiopathic short stature. Duplications flanking the SHOX gene (upstream or downstream of the intact SHOX gene involving conserved non-coding cis-regulatory DNA elements - CNEs) have been described but their clinical involvement is still difficult to understand. Results: We describe two cases with short stature and normal GH-IGF1 status. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (arrayCGH) identified in both cases heterozygous duplications involving downstream regions of SHOX gene, within CNEs (CNE8, CNE9 and CNE4, CNE5, CNE6, ECR1, CNE8, CNE9 and surrounding areas, respectively). One of the cases showed a maternally inherited duplication. Although every case has several particularities, we consider that duplications in these non-coding regions of SHOX gene may explain the short stature phenotype. Conclusion: To our knowledge, these are the first Romanian-reported cases of ISS with a large duplication of downstream SHOX enhancers CNEs region. The spectrum of phenotypic consequences and the exact mechanism of the presumed clinical expression of these genetic alterations still needs to be evaluated and described.

Adjuvant Use of PlasmaJet Device During Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: Results of the PlaComOv-study, a Randomized Controlled Trial in The Netherlands.

OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.

Assessment of the anti-hepatitis B vaccination efficacy in high risk children.

In October 1995, The Ministry of Health has initiated the national immunization program of newborns against hepatitis B. Owing to the frequency of asymptomatic Hepatitis B clinical forms in children, as well as the deficiencies in the surveillance system, the assessment of the vaccination efficacy can be performed objectively only by the detection of the prevalence of anti HBs antibodies in children to whom the complete three doses of immunization schedule have been administered (at 0, 2 and 6 months of age). We report in this study the results of a seroprevalence research carried out on a group of 272 children from orphanages who have been vaccinated. A protective anti HBs titer (> 10 mIU) was recorded only in 66.3% of cases; other 10 samples contained antibodies at a titer lower than the protective level. In the 80 children without seroconversion the presence of anti HBc antibodies (marker for the natural infection) was investigated. 30% of the seronegative children have anti HBc antibodies from which 54.2% have also HbsAg. Significant differences were recorded in the seroconversion level and in the geometric mean of titers between the various units in which sera were collected. In four orphanages (district Arad, Jassy, Sibiu and Teleorman) the seroconversion exceeded 90%, in 5 orphanages it was over 80% and in the others it ranged from 30% to 70%. The lowest seroconversions were recorded in the orphanages in Bucharest, Botosani, Galati and Olt. The possible causes of the low immunogenicity are analyzed: non-vaccination or incomplete vaccination; low immunoreactivity of children, many of whom are premature; high HbsAg carriage rate among the mother's etc. Although the evolution of the post vaccinal seroconversion is not a routine practice in the appraisement of Hepatitis B vaccine immunogenicity, our results require the extension of the study in order to adopt the most effective vaccinal strategy.

Low rates of seroconversion after hepatitis B vaccination in orphanges with high prevalence of virus carriers.

A serosurvey of Hepatitis B infection markers was conducted in two orphanages that adhered to Hepatitis B vaccination policy. In spite of comparable sizes (80-90 children per facility), housing conditions and infection control practices, the level of HbsAg endemicity was different in each unit in direct relation with the mean age of the children. The prevalence of HbsAg carriers and the interval spent in collectivity strongly affect the seroconversion rate after HB vaccination. Other elements that can explain the low seroconversion rate were: the proportion on fully vaccinated children, the number of vaccine administered doses and the delayed age at which childhood immunization schedule was initiated. In order to increase the protective antibody response, booster doses were administered to a limited number of nonseroconvertors or to children with a nonprotective level of anti-HBs antibody (< 10 UI). This intervention provides evidence of prompt rising in antibody titers, comparable with titers found in children with wild infection.

Herpesvirus-like DNA sequences in classic Kaposi's sarcomas.

Kaposi's sarcoma (KS) accounts for more than 15% of AIDS-related malignancies. The etiology of KS is unresolved but is postulated to be multifactorial, involving viruses and overexpression of cellular growth factors and/or oncogenes. Recently, herpesvirus-like sequences (KSHV) were identified with high prevalence in AIDS-KS (AKS), endemic KS, and in classic KS biopsies (CKS). To confirm the presence and the prevalence of the KSHV sequences, 18 CKS and 13 AKS samples were tested using polymerase chain reaction (PCR) analysis. To our knowledge this is the highest number of CKS samples that has ever been included in a single study, and it is also important that the biopsies were obtained from different institutions and geographical locations. KSHV sequences were detected in 100% of the AKS samples and 72% of the CKS biopsies using PCR analysis. The presence of the unique KSHV sequences was confirmed by direct sequencing of representative PCR products obtained from AKS and CKS samples. Reverse transcriptase (RT)-PCR experiments showed that the KSHV sequences were transcribed to mRNA in both AKS and CKS samples. Our results confirm that the putative new herpesvirus-like agent is associated with both AKS and CKS and may have an etiological role in the pathogenesis of this malignancy.

Occurrence of human papillomavirus and p53 gene mutations in Kaposi's sarcoma.

Epidemiological evidence indicates that a sexually transmitted agent might be involved in the etiopathogenesis of Kaposi's sarcoma (KS). The prevalence of human papillomaviruses (HPV) in KS has been the focus of several investigations that have reported conflicting data. In addition, mutations of the p53 gene, which are the most frequent genetic changes found in human tumors, are absent in HPV-positive cervical carcinomas leading to the hypothesis that the function of p53 in HPV-positive tumors is inactivated through binding to the E6 viral gene product. Thus, the present study was designed to investigate the presence of HPV and p53 gene mutations in 17 formalin-fixed, paraffin-embedded KS [7 acquired immunodeficiency syndrome-KS (AIDS-KS) and 10 classic KS] specimens. HPV 6 DNA was detected in an AIDS-KS specimen, and HPV 16 DNA was found in 3 classic KS specimens. Heterozygous mutations of the p53 gene were detected in five (24%) KS samples. No p53 mutations were detected in HPV-positive KS. The p53 mutations were mainly transversions (four of five). These data indicate that HPV may contribute to the pathogenesis of some cases of KS and that p53 alteration may represent a key event in the progression of the malignancy.

AIDS in Romania.

Of the 1446 AIDS cases reported in Romania, 79% were in the pediatric age group. Of these children, 28% lived with their families, 30% were orphans, and 42% were abandoned. Among the AIDS-affected children, 32% were less than 1 year old and 67% were 1-4 years old. The natural history of AIDS in Romania was characterized by a high death rate from opportunistic infections. Chronic undernutrition imposed by the communist program of "rational feeding of the population," immunodepression induced by the radiation generated by the accident at Chernobyl, hard physical work in an environment intensely polluted by industrial waste, excessive use of injectable therapies and transfusions of HIV-untested blood, lack of education of the medical staff and the population, and tourism have contributed to the AIDS epidemic in Romania. Kaposi's sarcoma was infrequent (7.7%) in AIDS patients. However, a significant number of European-type Kaposi's sarcoma cases with negative tests for the HIV infection were reported.

Study of specific immune response to unadsorbed concentrated tetanus vaccine administered by intradermal route to non-immunized persons in the last ten years.

Investigations of anti-tetanus response, in 404 subjects, most of them aged 60, being non-immunized for at least 10 years, stressed out the fact that 28.7% were not protected and 6.18% presented a protecting titer of 0.01 IU/ml, evaluated by "in vivo" protection test in mice. Some subjects were immunized with unadsorbed Tetanus vaccine (10 Lf/0.1 ml/dose) by i.d. route, using Jet-injector, and the others with adsorbed Tetanus vaccine (0.5 ml/dose), by i.m. route, using the needle and syringe. The vaccines were well tolerated and adverse reactions were not recorded. After 30 days, a single vaccine dose produced a protecting effect in 97.45% of non-protected subjects, belonging to i.d. immunized group, and also in 93.33% belonging to i.m. immunized group. 30 days after the administration of a second dose, protection set up in all subjects, no matter of vaccine type and administration route used. For a continuous reduction of tetanus morbidity, the authors suggest a specific periodical immunization of non-protected persons, selected by serological screening, using unadsorbed Tetanus vaccine, administered by i.d. route by means of the Jet-injector.