High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Autosomal Dominant Polycystic Kidney Disease: What Do We Need To Know For Counselling?

In the new millennium, few kidney diseases changed their perspectives as much as autosomal dominant polycystic kidney disease (ADPKD). New diagnostic approaches, including the evaluation of renal or liver volume by computerised tomography (CT) scan, the detection of cyst infections by positron emission tomography (PET) scan, and new therapeutic approaches (including vaptans, mTOR inhibitors, and somatostatin analogues) pose new clinical and ethical dilemmas. Therefore, the analysis of the recent advances offers an occasion for reviewing our counselling policy. The aim of this narrative review is to discuss a few crucial points concerning counselling in ADPKD: should all ADPKD patients undergo genetic testing for characterisation of the involved gene? What is the role of prenatal counselling and preimplantation selection? Should all ADPKD patients be followed in a nephrology clinic? Which imaging to use in which patients? Whom should we treat, when, and by which drugs, and how to communicate the treatment options? The working conclusions highlight the trends towards earlier referral of ADPKD patients, the importance of offering the diet options, including low-salt, high-water intake, difficult to follow, but devoid of side-effects, and the expectancy for the new therapeutic options, alone or in combination, aimed at reduction of cyst volume and/or control of cyst growth

Quality of life in patients with endometrial cancer treated with or without systematic lymphadenectomy

Objective: To compare the quality of life (QoL) of women affected by endometrial cancer treated with surgery with or without systematic lymphadenectomy. Study design: Consecutive patients affected by stages I and II endometrial cancer and treated with surgery between 2008 and 2011 were selected. Eligible subjects were divided into two groups: Group A consisted of 36 patients who had hysterectomy plus bilateral salpingo-oophorectomy without lymphadenectomy; Group B consisted of 40 patients who had hysterectomy plus salpingo-oophorectomy plus pelvic and aortic lymphadenectomy. The EORTC Quality of Life Questionnaire-Cancer Module (QLQ-C30) and Quality of Life Questionnaire-Endometrial Cancer Module (QLQ-EN24) were administered to selected patients. All data were recorded and then analyzed using the scoring manual of the EORTC Quality of Life Group. Results: Among symptom scales, only lymphedema gave a statistically significant difference among two groups, with a score of 10.64 ± 17.43 in Group A and 21.66 ± 24.51 in Group B (p = 0.0285). The p value obtained comparing the "Global Health Status" (items 29 and 30) in Group A and in Group B was not statistically significant. Conclusion: Lymphadenectomy did not influence negatively global health status, but lymphadenectomy maintained its importance in determining a patient's prognosis and in tailoring adjuvant therapies. We therefore support its practice as part of the surgical procedure in patients affected by high risk endometrial cancer. © 2013 Elsevier Ireland Ltd. All rights reserved

Feasibility and safety of carboplatin plus paclitaxel as neoadjuvant chemotherapy for locally advanced cervical cancer: a pilot study

The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Between June 2007 and May 2012, all patients with a diagnosis of locally advanced cervical cancer (IB2-IIB) were eligible for this protocol. All patients have received 3 cycles of carboplatin (AUC6) and paclitaxel 175 mg/mq in neoadjuvant setting. The NACT-induced toxicity and the response to treatment were evaluated according to the World Health Organization (WHO) criteria. After NACT, all patients with complete or partial response were submitted to classical radical hysterectomy type III or C2, according to different classifications, and were submitted to four adjuvant cycles of platinum-based chemotherapy. The primary endpoints of the study were to evaluate the efficacy and feasibility of carboplatin regimen. Thirty-five patients with locally advanced cervical cancer were considered. A total of 23 patients completed 3 cycles of NACT. The overall clinical response rate after NACT was 78.3 % including 43.5 % (n = 10) with complete response, 34.8 % (n = 8) with partial response, 17.4 % (n = 4) with stable disease and 4.3 % (n = 1) of those who suffered disease progression. The most common toxicity was haematologic, nausea/vomiting and neuropathy with grades 1 and 2 and occurred in 56.5, 56.5 and 17.4 %, respectively. No renal toxicity was registered. Our results suggest that carboplatin is a well-tolerated drug with a response rate similar to standard cisplatin. Then, it represents, in neoadjuvant setting, a valid alternative in patients affected by locally advanced cervical cancer. © 2013 International Society of Oncology and BioMarkers (ISOBM)

Preliminary Evaluation of Sedentary Lifestyle in Italian Children after Solid Transplant: What Role Could Physical Activity Play in Health? It Is Time to Move

Background: Advances in the medical–surgical field have significantly increased survival after solid organ transplantation in the pediatric population. However, these patients are predisposed to the development of long-term complications (e.g., cardiovascular disease). The therapeutic role of physical activity (PA) to counteract these complications is well known. The purpose of the study was to investigate the level of PA in a pediatric population after solid organ transplantation. Methods: In the first 4 weeks at the beginning of the school year, the Physical Activity Questionnaire for Older Children and Adolescents was administered to young patients who had previously undergone solid transplants at our institute. Results: Questionnaires of 49 patients (57.1% female, mean age 13.2 ± 3.5 years) were analyzed and 32.7% of subjects did not perform any exercise during school physical education classes. Only 24% practiced a moderate quantity of exercise in the previous week (2–3 times/week) and 72% engaged in sedentary behaviors during weekends. Conclusions: Preliminary data confirmed that young recipients are still far from meeting the minimum indications of the World Health Organization on PA and sedentary behavior. It will be necessary to increase their involvement in PA programs in order not only to increase their life expectancy but also to improve their quality of life

Unusual presentation of Denys-Drash syndrome in a girl with undisclosed consumption of biotin

We describe a 46,XX girl with Denys-Drash syndrome (DDS), showing both kidney disease and genital abnormalities, in whom a misdiagnosis of hyperandrogenism was made. A 15 year-old girl was affected by neonatal nephrotic syndrome, progressing to end stage kidney failure. Hair loss and voice deepening were noted during puberty. Pelvic ultrasound and MRI showed utero-tubaric agenesis, vaginal atresia and urogenital sinus, with inguinal gonads. Gonadotrophin and estradiol levels were normal, but testosterone levels increased up to 285 ng/dL at Tanner stage 3. She underwent prophylactic gonadectomy and histopathology reported fibrotic ovarian cortex containing numerous follicles in different maturation stages and rudimental remnants of Fallopian tubes. No features of gonadoblastoma were detected. Unexpectedly, testosterone levels were found elevated 4 months after gonadectomy (157 ng/dL). Recent medical history revealed a chronic assumption of a high daily dose of biotin, as a therapeutic support for hair loss. Laboratory immunoassay instruments used streptavidin-biotin interaction to detect hormones and, in competitive immunoassays, high concentrations of biotin can result in false high results. Total testosterone, measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), was found within reference intervals. Similar testosterone levels were detected repeating the immunoassay two weeks after biotin uptake interruption. Discordance between clinical presentation and biochemical results in patients taking biotin, should rise the suspicion of erroneous results. Improved communication among patients, health care providers, and laboratory professionals is required concerning the likelihood of biotin interference with immunoassays

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios

Expression of αV-Integrins in Uterine Serous Papillary Carcinomas; Implications for Targeted Therapy With Intetumumab (CNTO 95), a Fully Human Antagonist Anti-αV-Integrin Antibody

Objective:Uterine serous papillary carcinoma (USPC) is an aggressive variant of endometrial cancer characterized by an innate resistance to chemotherapy and poor prognosis. In this study, we evaluated the expression of αV-integrins in primary USPC cell lines and the in vitro ability of intetumumab (CNTO 95), a fully human monoclonal antibody against αV-integrins, to inhibit USPC cell adhesion and migration.Materials and Methods:The surface expression of integrins belonging to the αV-family, including αVβ3, αVβ5, and αVβ6, was evaluated in 6 primary USPC cell lines using flow cytometry analysis. To test the ability of intetumumab to inhibit USPC cell adhesion and migration, adhesion assays in the presence of vitronectin and migration assays through an 8.0-μm pore polycarbonate membrane also were performed.Results:We found high expression of the αV-subunit on the cell surface of all 6 primary USPC cell lines tested (100% positive cells; mean fluorescence intensity range, 13.1-39.5). When the expression of single heterodimeric integrins was evaluated, αVβ3, αVβ5, and αVβ6 were expressed on 37.5%, 32.0%, and 16.3% of cells (mean fluorescence intensity range, 6.5-16.2, 9.2-32.5, and 6.2-11.5, respectively). Importantly, in functional assays, low doses of intetumumab were effective in inhibiting adhesion (0.15 μg/mL, P = 0.003) and migration (1.25 μg/mL P = 0.02) of primary USPC cell lines.Conclusions:The αV-integrins are overexpressed on the cell surface of primary USPC cell lines. Intetumumab may significantly inhibit USPC cell adhesion and migration pathways and may therefore represent a novel treatment option for patients harboring this rare but highly aggressive variant of endometrial cancer