A systematic literature review of the human papillomavirus prevalence in locally and regionally advanced and recurrent/metastatic head and neck cancers through the last decade: The "ALARM" study.

AIMS: The aim of this systematic literature review was to provide updated information on human papillomavirus (HPV) prevalence in locally and regionally advanced (LA) and recurrent/metastatic (RM) head and neck cancer (HNC) worldwide. METHODS: Electronic searches were conducted on clinicaltrials.gov, MEDLINE/PubMed, Embase, and ASCO/ESMO journals of congresses for interventional studies (IS; Phase I-III trials) as well as MEDLINE and Embase for non-interventional studies (NIS) of LA/RM HNC published between January 01, 2010 and December 31, 2020. Criteria for study selection included: availability of HPV prevalence data for LA/RM HNC patients, patient enrollment from January 01, 2010 onward, and oropharyngeal cancer (OPC) included among HNC types. HPV prevalence per study was calculated as proportion of HPV+ over total number of enrolled patients. For overall HPV prevalence across studies, mean of reported HPV prevalence rates across studies and pooled estimate (sum of all HPV+ patients over sum of all patients enrolled) were assessed. RESULTS: Eighty-one studies (62 IS; 19 NIS) were included, representing 9607 LA/RM HNC cases, with an overall mean (pooled) HPV prevalence of 32.6% (25.1%). HPV prevalence was 44.7% (44.0%) in LA and 24.3% (18.6%) in RM. Among 2714 LA/RM OPC patients from 52 studies with available data, mean (pooled) value was 55.8% (50.7%). The majority of data were derived from Northern America and Europe, with overall HPV prevalence of 46.0% (42.1%) and 24.7% (25.3%) across studies conducted exclusively in these geographic regions, respectively (Northern Europe: 31.9% [63.1%]). A "p16-based" assay was the most frequently reported HPV detection methodology (58.0%). CONCLUSION: Over the last decade, at least one quarter of LA/RM HNC and half of OPC cases studied in IS and NIS were HPV+. This alarming burden is consistent with a potential implication of HPV in the pathogenesis of at least a subgroup of HNC, underscoring the relevance of HPV testing and prophylaxis to HNC prevention and management.

Real-world management practices and characteristics of patients with advanced melanoma initiated on immuno-oncology or targeted therapy in the first-line setting during the period 2015-2018 in Greece. The 'SUMMER' study: a retrospective multicenter chart review project.

This study primarily aimed to generate real-world evidence (RWE) on the profile and first-line treatment (1LT) patterns of patients with advanced (unresectable Stage III/metastatic) cutaneous melanoma initiated on immuno-oncology (IO)- or targeted therapy (TT)-based 1LT between 1 January 2015 and 1 January 2018 (index period), in routine settings of Greece. This was a multicenter, retrospective chart review study. Eligible consented (unless deceased, for whom consent was waived by the hospital) patients were consecutively included by six oncology clinics. The look-back period extended from informed consent or death to initial melanoma diagnosis. Between 9 Junuary 2021 and 9 February 2022, 225 eligible patients (all Caucasians; 60.4% male; 35.6% diagnosed with de novo advanced melanoma) were included. At 1LT initiation, median age was 62.6 years; 2.7/6.7/90.7% of the patients had Stage IIIB/IIIC/IV disease and 9.3% were unresected. Most frequent metastatic sites were the lung (46.7%), non-regional nodes (33.8%), and liver (20.9%). Among patients, 98.2% had single primary melanoma, 45.6% had disease localized on the trunk, and 63.6% were BRAF-mutant. Of the patients, 45.3% initiated 1LT with an IO-based, 53.3% with a TT-based regimen, and three patients (1.3%) received TT-based followed by IO-based or vice versa. Most common 1LT patterns (frequency ≥10%) were BRAFi/MEKi combination (31.6%), anti-PD-1 monotherapy (25.3%), BRAFi monotherapy (21.8%), and anti-CTLA-4 monotherapy (17.8%). Most frequent regimens were Dabrafenib+Trametinib in 25.3%, and monotherapies with Pembrolizumab/Ipilimumab/Vemurafenib/Dabrafenib in 23.6/17.8/11.1/10.7% of patients, respectively. SUMMER provides RWE on 1LT strategies and profile of patients initiated 1L IO- or TT-based therapy in Greece during the 3-year index period.

HTA and Reimbursement Status of Metastatic Hormone­Sensitive Prostate Cancer, Non-Metastatic Castration-Resistant Prostate Cancer, and Metastatic Castration-Resistant Prostate Cancer Treatments in Europe: A Patient Access Landscape Review.

Background: Prostate cancer is the second most common cancer in men, with up to one-third of men being diagnosed in their lifetime. Recently, novel therapies have received regulatory approval with significant improvement in overall survival for metastatic castration-resistant prostate cancer, metastatic hormone-sensitive prostate cancer, and nonmetastatic castration-resistant prostate cancer. To improve decision-making regarding the value of anticancer therapies and support standardized assessment for use by health technology assessment (HTA) agencies, the European Society for Medical Oncology (ESMO) has developed a Magnitude of Clinical Benefit Scale (MCBS). Objective: This review aimed to map HTA status, reimbursement restrictions, and patient access for 3 advanced prostate cancer indications across 23 European countries during 2011-2021. Methods: HTA, country reimbursement lists, and ESMO-MCBS scorecards were reviewed for evidence and data across 26 European countries. Results: The analysis demonstrated that only in Greece, Germany, and Sweden was there full access across all included prostate cancer treatments. Treatments available for metastatic castration-resistant prostate cancer were widely reimbursed, with both abiraterone and enzalutamide accessible in all countries. In 3 countries (Hungary, the Netherlands, and Switzerland), there was a statistically significant difference (P<.05) between status of reimbursement and ESMO-MCBS "substantial benefit" (score of 4 or 5) vs "no substantial benefit" (score <4). Conclusion: Overall, the impact of the ESMO-MCBS on reimbursement decisions in Europe is unclear, with significant variation across the countries included in this review.

Alexandra General Hospital in Athens: Historical Connections to the Greek Royal Family.

Princess Alexandra of Greece (1870-1891), the eldest daughter of King George I of Greece (1845-1913), was known as the "beloved daughter of the Athenians". Her death at the age of 21 in 1891 due to a pregnancy complication caused nationwide grief. To honour her, the Alexandra Maternity Hospital in Athens was named in her memory. Affiliated with the University of Athens, Alexandra Maternity Hospital researches pregnancy and newborn care, including complications and maternal mortality. Today, the hospital contains various clinical and laboratory departments providing patients with exceptional health care.

Risk for Venous Thromboembolic Events in Patients With Advanced Urinary Tract Cancer Treated With First-Line Chemotherapy.

BACKGROUND: Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. PATIENTS AND METHODS: Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. RESULTS: A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. CONCLUSION: Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Systemic therapy in cervical cancer: 30 years in review.

Advanced-inoperable cervical cancer is a challenging entity due to increased percentage of locoregional and distant recurrences. Furthermore, recurrent cervical cancer not amenable to radical treatment as well as de novo metastatic disease are considered incurable with dismal prognosis. Well-designed clinical trials conducted during the last 30 years have revealed the active chemotherapeutic agents as well as their optimal combinations. The rational approach that has led to the current treatment algorithms as well as the introduction of targeted therapies based on the knowledge of the molecular pathogenesis of the disease are discussed in this review.

Is There a Role for Double J Stent Culture in Contemporary Urology?

INTRODUCTION: To present the incidence of bacterial colonization on ureteral double J stents (DJS); isolate the uropathogens; define the rate of multi-resistant bacteria strains (MRBS) and present their clinical importance. MATERIALS AND METHODS: The whole body of 105 DJSs was examined for the presence of uropathogens. RESULTS: The main etiology for stent placement was lithiasis (57.1%). The most frequently cultured microorganisms were staphylococcus (28.6%). Forty-four stents hosted MRBS. 25 (23.8%), 10 (9.5%) and 8 (7.6%) of the patients were affected by malignancy, diabetes mellitus and chronic renal failure respectively. Apart from the female gender, none of the examined factors (age, duration of stenting and chronic diseases) was correlated with the colonization or the presence of MRBS. Eleven of the 61 stented patients (18%) who were operated upon developed a febrile urinary tract infections (UTI). In 7 of them the stent hosted MRBS (63.6%). After taking into consideration the sensitivity report, we altered our initial empirical antibacterial prophylaxis to targeted antibacterial treatment in the patients with MRBS with rapid remission of their infection and no urosepsis event. CONCLUSION: The knowledge of bacteriologic flora of DJS can be very helpful in an evidence-based prophylactic and therapeutic practice. Stent examination could be recommended in high-risk cases of developing UTI and sepsis after a urologic operation.

Case-mix adjustment approach to benchmarking prevalence rates of nosocomial infection in hospitals in Cyprus and Greece.

OBJECTIVE: To examine the effect of heterogeneous case mix for a benchmarking analysis and interhospital comparison of the prevalence rates of nosocomial infection. DESIGN: Cross-sectional survey. SETTING: Eleven hospitals located in Cyprus and in the region of Crete in Greece. METHODS: The survey included all inpatients in the medical, surgical, pediatric, and gynecology-obstetrics wards, as well as those in intensive care units. Centers for Disease Control and Prevention criteria were used to define nosocomial infection. The information collected for all patients included demographic characteristics, primary admission diagnosis, Karnofsky functional status index, Charlson comorbidity index, McCabe-Jackson severity of illness classification, use of antibiotics, and prior exposures to medical and surgical risk factors. Outcome data were also recorded for all patients. Case mix-adjusted rates were calculated by using a multivariate logistic regression model for nosocomial infection risk and an indirect standardization method.Results. The overall prevalence rate of nosocomial infection was 7.0% (95% confidence interval, 5.9%-8.3%) among 1,832 screened patients. Significant variation in nosocomial infection rates was observed across hospitals (range, 2.2%-9.6%). Logistic regression analysis indicated that the mean predicted risk of nosocomial infection across hospitals ranged from 3.7% to 10.3%, suggesting considerable variation in patient risk. Case mix-adjusted rates ranged from 2.6% to 12.4%, and the relative ranking of hospitals was affected by case-mix adjustment in 8 cases (72.8%). Nosocomial infection was significantly and independently associated with mortality (adjusted odds ratio, 3.6 [95% confidence interval, 2.1-6.1]). CONCLUSION: The first attempt to rank the risk of nosocomial infection in these regions demonstrated the importance of accounting for heterogeneous case mix before attempting interhospital comparisons.

Effect of plasmin, plasminogen activators and a plasmin inhibitor on bovine in vitro embryo production.

In the present study, four experiments were conducted to investigate the possible effects of plasminogen activators (urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA)), plasmin, and a plasmin inhibitor (epsilon-aminocaproic acid (epsilon-ACA)) on different stages of bovine in vitro embryo production (IVP). The concentrations of these modifiers in IVP media were conditioned according to the plasminogen activator activity of bovine preovulatory follicular fluid. Media were modified in a single phase of IVP with an 18 h or 24 h incubation for in vitro maturation (IVM) and a 24 h or 48 h incubation for the IVF or in vitro culture (IVC), respectively. After IVM the oocytes were either fixed and stained or underwent IVF and IVC. The main findings were: (1) plasmin added to the 18 h IVM medium increased maturation rate without affecting fertilisation or embryo development rates; (2) t-PA added to the IVF medium significantly increased cleavage; (3) u-PA added to the IVC medium significantly increased embryo development rates; (4) the efficiency of all phases of IVP was reduced after the addition of epsilon-ACA; and (5) plasminogen addition had no effect in any IVP phase tested. We conclude that the members of the plasminogen activator-plasmin system contribute in different ways to bovine IVM, IVF and IVC.