Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mutational Pattern in the Fourth Pandemic Phase in Greece.

The aim of this study is to investigate the circulating variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Athens and from rural areas in Greece during July and August 2021. We also present a rapid review of literature regarding significant SARS-CoV-2 mutations and their impact on public health. A total of 2500 nasopharyngeal swab specimens were collected from suspected COVID-19 cases (definition by WHO 2021b). Viral nucleic acid extraction was implemented using an automatic extractor and the RNA recovered underwent qRT-PCR in order to characterize the specimens as positive or negative for SARS-CoV-2. The positive specimens were then used to identify specific Spike gene mutations and characterize the emerging SARS-CoV-2 variants. For this step, various kits were utilized. From the 2500 clinical specimens, 220 were tested positive for SARS-CoV-2 indicating a prevalence of 8.8% among suspected cases. The RT-PCR Ct (Cycle threshold) Value ranged from 19 to 25 which corresponds to medium to high copy numbers of the virus in the positive samples. From the 220 positive specimens 148 (67.3%) were from Athens and 72 (32.7%) from Greek rural areas. As far as the Spike mutations investigated: N501Y appeared in all the samples, D614G mutation appeared in 212 (96.4%) samples with a prevalence of 87.2% in Athens and 98.6% in the countryside, E484K had a prevalence of 10.8% and 12.5% in Athens and the rural areas, respectively. K417N was found in 18 (12.2%) samples from Athens and four (5.6%) from the countryside, P681H was present in 51 (34.5%) Athenian specimens and 14 (19.4%) specimens from rural areas, HV69-70 was carried in 32.4% and 19.4% of the samples from Athens and the countryside, respectively. P681R had a prevalence of 87.2% in Athens and 98.6% in rural areas, and none of the specimens carried the L452R mutation. 62 (28.2%) samples carried the N501Y, P681H, D614G and HV69-70 mutations simultaneously and the corresponding variant was characterized as the Alpha (UK) variant (B 1.1.7). Only six (2.7%) samples from the center of Athens had the N501Y, E484K, K417N and D614G mutations simultaneously and the virus responsible was characterized as the Beta (South African) variant (B 1.351). Our study explored the SARS-CoV-2 variants using RT-PCR in a representative cohort of samples collected from Greece in July and August 2021. The prevalent mutations identified were N501Y (100%), D614G (96.4%), P681R (90.1%) and the variants identified were the Delta (90.1%), Alpha (28.2%) and Beta (2.7%).

Computed Tomography-Guided Percutaneous Microwave Ablation for Renal Cell Carcinoma: Impact of Tumor Size on the Progression Survival Rates.

The aim of the present study was to evaluate the safety and efficacy of computed tomography (CT)-guided percutaneous microwave ablation (MWA) of renal cell carcinoma (RCC) along with identifying prognostic factors affecting the progression survival rate. Institutional database retrospective research identified 69 patients with a biopsy proven solitary T1a (82.6%) or TIb (17.4%) RCC who have underwent percutaneous CT-guided MWA. Kaplan-Meier survival estimates for events were graphed and Cox regression analysis was conducted. Mean patient age was 70.4 ± 11.5 years. Mean size of the lesions was 3 ± 1.3 cm. Mean follow up time was 35.6 months (SD = 21.1). The mean progression free survival time from last ablation was 84.2 months. For T1a tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 91.2% (SE = 3.7%), 91.2% (SE = 3.7%) and 87.5% (SE = 4.4%); the recurrence free survival rate for T1a RCC was 94.9%. For T1b tumors, the cumulative progression free survival rate for 1, 6, 12 and 36 months were 100% (SE = 0%), 63.6% (SE = 14.5%), 63.6% (SE = 14.5%) and 63.6% (SE = 14.5%). Grade 1 complications were recorded in 5 (7.2%) patients. Significantly greater hazard for progression was found in cases with a tumor size > 4 cm (HR = 9.09, p = 0.048). No statistically important difference regarding tumor progression was recorded between T1a tumors with a diameter ≤3 cm and >3 cm. In summary, the results of the present study show that CT guided percutaneous MWA is an effective technique for treatment of T1a renal cell carcinomas, irrespective of tumor size. T1b tumors were associated with higher progression rates.

Association of TNF-α 308G/A and LEPR Gln223Arg Polymorphisms with the Risk of Type 2 Diabetes Mellitus.

The objective of the present study was to identify the association of the TNF-α- 308G/A and leptin receptor (LEPR) Gln223Arg polymorphisms with the risk of development of type 2 diabetes mellitus (T2DM). METHODS: A total of 160 volunteers were studied: 108 with T2DM and 52 participants as control, who served as the control group. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the genomic region of TNF-α- 308G/A and LEPR Gln223Arg were carried out. RESULTS: The frequency of LEPR Gln223Arg genotypes in T2DM and control groups showed significant differences in the distribution of genotypes (p < 0.05). The frequency also of TNF-α- 308G/A genotypes in T2DM and control subjects showed significant differences in the distribution of genotypes (p < 0.05). CONCLUSION: Our results indicate that there are significant differences in the distribution of genotypes and alleles between the individuals with T2DM and control subjects (p < 0.05).

Pelvic Exenteration Put into Therapeutical and Palliative Perspective: It Is Worth to Try.

Pelvic exenteration (PE) is one of the most drastic operations in surgical oncology, associated with severe morbidity and mortality. The objective of our study was to review our experience of PE in terms of surgical characteristics, complications, and overall survival. All patients who had PE surgery between January 1999 and December 2015 were identified. Patients with verified distant metastatic disease were excluded. Patients with advanced pelvic tumors experiencing incapacitating postradiation severe damages were included. The following parameters were recorded: age, sex, indication for surgery, tumor histology, type of exenteration, urinary tract and colon reconstruction methods, operative time, blood transfusion, intensive care unit admissions, length of hospital stay and readmissions, and characteristics of perioperative morbidity and mortality. A total of 25 patients were submitted to PE by our surgical team. Most of the patients suffered from cervical cancer followed by bowel cancer. There was no perioperative mortality. Early postoperative complications ensued in 56% of the patients. Most complications involved the urinary system. Five years survival was estimated at 38%. Most patients (n = 9, 36%) died due to their primary disease, 5 (20%) died because of complications following operation, and 2 (8%) died because they denied oral feeding, which was associated with depression. Patients with a variety of malignancies can benefit from PE. Meticulous surgical technique, perioperative care, counseling, and nutritional support play an important role.

Fertility Risk Assessment and Preservation in Male and Female Prepubertal and Adolescent Cancer Patients.

Cancer represents the second cause of death in prepubertal children and adolescents, although it is currently associated with an overall survival rate of 80%-85%. The annual incidence rate is 186.6 per 1 million children and adolescents aged up to 19 years. Both disease and treatment options are associated with life-altering, long-term effects that require monitoring. Infertility is a common issue, and as such, fertility preservation represents an essential part in the management of young patients with cancer who are at risk of premature gonadal failure. This review deals with the up-to-date available data on fertility risk assessment and preservation strategies that should be addressed prior to antineoplastic therapy in this vulnerable subgroup of cancer patients.

Evaluation of acute toxicity and symptoms palliation in a hypofractionated weekly schedule of external radiotherapy for elderly patients with muscular invasive bladder cancer.

AIM: To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. MATERIALS AND METHODS: Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. RESULTS: The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS: The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes.

Evaluation of Acute Toxicity and Symptoms Palliation in a Hypofractionated Weekly Schedule of External Radiotherapy for Elderly Patients with Muscular Invasive Bladder Cancer

Aim To evaluate acute toxicity and symptoms palliation of a weekly hypofractionated 3DCRT schedule as radical treatment in elderly patients with organ confined bladder cancer cT1-2N0. Materials and Methods Between February 2005 and June 2011, 58 prospectively selected patients diagnosed with organ confined bladder cancer were treated with external 3DCRT (4-field arrangement). All candidates were medically inoperable, with poor performance status, and with age ranged from 75 to 88 years (median 78). A dose of 36 Gy in 6 weekly fractions was prescribed. The primary study endpoints were the evaluation of haematuria, dysuria, frequency and pain palliation as well as the acute toxicity according to the RTOG/EORTC scale: an assessment was performed at baseline, during and 3 months after radiotherapy, while the maximum reported score was taken into account. Results The gastrointestinal acute toxicities were 13/58 (22.4%) and 5/58 (5.6%), for grade I and II respectively. The genitourinary acute toxicities were 19/58 (32.7%) and 10/58 (17.2%), for grade I and II respectively. In terms of clinical outcome, 55/58 patients (94.8%) reported palliation of haematuria, while 19 out of 58 reported no change in frequency and dysuria. All patients reported significant improvement (P < 0.01) for pain, concerning the visual analogue score before and after radiotherapy. The median progression free survival was 14 months. CONCLUSIONS The incidence of patient-reported acute toxicity following weekly hypofractionated external 3DCRT is low while the symptom palliation compares very favorably with other reported outcomes. .

Tissue inhibitor of metalloproteinase-2 as a multifunctional molecule of which the expression is associated with adverse prognosis of patients with urothelial bladder carcinomas.

PURPOSE: Tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase (MMP) activity controlling the breakdown of extracellular matrix components and, thus, play an important role in the process of invasion and metastasis. Moreover, there are several new functions, growth control, apoptosis, and angiogenesis-, in which TIMPs seem to be involved. The aim of this study was to elucidate the role of TIMP-2 in human urothelial cancer assessing TIMP-2 protein expression in 106 urothelial bladder carcinomas and evaluating its importance relative to clinicopathologic parameters (age, gender, histological grade, and stage) and patient survival, as well as to markers associated with cell growth and apoptosis (Ki-67, p53, and bcl-2). EXPERIMENTAL DESIGN: Immunohistochemistry (avidin-biotin complex method-horseradish peroxidase) was performed to detect TIMP-2, Ki-67, p53, and bcl-2 proteins using monoclonal and polyclonal antibodies. Statistical analysis was univariate and multivariate. RESULTS: TIMP-2 immunohistochemical expression was observed in stromal fibroblasts and in cancerous cells in 26.4% and 69.8% of cases, respectively. TIMP-2 stromal but not cancerous cell expression associated significantly with the high histological grade of carcinomas (P < 0.0001) and the advanced stage of the disease (P = 0.001). TIMP-2 either stromal or cancerous cell expression correlated significantly with the expression of Ki-67 proliferation indice (P = 0.02 and P = 0.044, respectively) and the mutant p53 protein (P = 0.043 and P = 0.045, respectively). In univariate survival analysis patients with positive TIMP-2 stromal cell immunohistochemical expression had a significantly worse overall survival in comparison with TIMP-2 stromal cell-negative patients (log rank test: P = 0.0002). However, in multivariate survival analysis the only independent survival factors were the stage of the disease and patient age. CONCLUSIONS: TIMP-2 protein expression in either the stromal or cancerous cells is associated with the proliferation index Ki-67 and the apoptosis-related protein p53. These findings are in keeping with in vitro studies reporting a growth-promoting ability of TIMP-2 and its involvement in apoptosis regulation. On the other hand, TIMP-2 stromal cell expression only was associated with adverse prognosis of urothelial bladder cancer patients.