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From a cohort of 1352 consecutive patients admitted with coronavirus disease (Covid-19) to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied 688 patients with arterial hypertension (254 deaths) to assess whether use of renin-angiotensin system inhibitors (RASIs) prior to hospital admission affects mortality from Covid-19. Prior use of RASIs was associated with a lower mortality in the over-68 group of patients, whereas no evidence of a similar effect (whether protective or adverse) was found in the younger group. There was positive relative excess due to a statistically significant (p =0.001) interaction between prior RASI exposure and an age greater than 68 years, corresponding to a positive relative excess risk. Next we used the subgroup of 411 hypertensive patients older than 68 yrs to separately assess the effects prior use of two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs) and angiogiotensin receptor blockers (ARBs), by comparing these two exposures with no exposure to RASIs. We found both prior use of ACEIs and prior use of ARBs to be associated with a lower Covid-19 mortality, after adjusting for 32 medical history variables via propensity score matching. (ORACEI = 0.57, 95%CI 0.36 to 0.91, p =0.018) (ORARB = 0.49, 95%CI 0.29 to 0.82, p =0.006).

Background Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients. Methods Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization. Results 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 ± 14.5 years (vs 67.8 ± 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO2/FiO2 was similar between men and women (228 [IQR, 134–273] vs 238 mmHg [150–281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan–Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687). Conclusion Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.

Immunosuppressive acidic protein (IAP) and squamous cell carcinoma (SCC) serum levels were assayed in a group of 63 primary cervical cancer patients. IAP serum levels were significantly higher in cancer patients (median, 630 micrograms/ml; range, 290-1150) than in controls (median, 290 micrograms/ml; range, 135-775) (P0.01). The percentage of IAP-positive (613 micrograms/ml) cases was 50.7%. SCC serum levels were found to be above 2.5 ng/ml in 73% of cervical cancer patients, and in 6% of controls. A statistically significant correlation was observed between IAP and SCC levels in cancer patients (r = 0.35, P0.004). When IAP and SCC were considered together the overall sensitivity was 87.3% and an improvement of both predictive value of negative test and accuracy without any significant reduction of predictive value of positive test was found. IAP status correlated with metastatic lymph node involvement. A statistically significant association between a shorter survival and high serum LAP levels was observed. The 24-month overall survival (OS) was 92% for IAP- cases with respect to 65% for IAP+ cases (P = 0.036). In the univariate analysis, advanced stage of disease, clinical parametrial involvement, and lymph node involvement were also associated with poor survival. In the multivariate analysis IAP status showed a statistically significant association with poor survival (P = 0.049), together with lymph node involvement (P = 0.007) and advanced stage of disease (P = 0.008).

A sensitive and specific method for the quantification of sufentanil in human plasma by liquid chromatography coupled with tandem mass spectrometry has been developed. Fentanyl was used as the internal standard. Rapid sample preparation involved purification on a C(18) solid-phase extraction column. Chromatographic separation of the analytes was obtained using an RP-C(18) mu-HPLC column. LC-MS-MS detection was performed by atmospheric pressure ionisation (API) source equipped with an ionspray (IS) interface operating in the positive ion mode. For unambiguous substance confirmation, three analyte precursor-product ion combinations were monitored during multiple reaction monitoring (MRM) LC-MS-MS analysis. The method's performance characteristics were evaluated in blank and spiked control plasma samples. Overall accuracy (relative error, R.E., %), repeatability (relative standard deviations, R.S.D., %) and within-laboratory reproducibility (R.S.D., %) ranged from -9.28 to -2.71%, from 6.42 to 2.82% and from 13.52 to 6.06%, respectively, for sufentanil. The limit of quantification for sufentanil in human plasma samples was 0.3 ng ml(-1). Due to its high sensitivity and specificity, the method was successfully employed for sufentanil determination in maternal plasma samples collected immediately before epidural administration of a single sufentanil dose to women in labour, 20 min after drug administration, and at birth in arterial and venous umbilical cord plasma samples from the newborn babies. Research is in progress to adopt the method for performance of complete pharmacokinetic studies of sufentanil in human plasma.

BACKGROUND Due to the high prevalence of perioperative major morbidity and the difficulties in achieving surgical disease free margins, surgery has had no role in the treatment of patients with Stage III cervical carcinoma. METHODS Forty-two women with International Federation of Gynecology and Obstetrics (FIGO) Stage III cervical carcinoma responding to platinum-based neoadjuvant chemotherapy underwent the maximum surgical effort, comprised of a modified type IV-V radical hysterectomy (37 patients) or anterior pelvectomy (5 patients) with systematic pelvic and aortic lymphadenectomy. Feasibility, modifications of surgical technique, and pathologic and clinical data were analyzed. RESULTS Surgery was feasible in all 42 patients intraoperatively selected. Disease free margins were achieved in all but one patient. The median operating time was 390 minutes, and the median estimated blood loss was 800 mL. In the last series of patients, these figures declined to 320 minutes and 600 mL, respectively. Major morbidity consisted of severe intraoperative hemorrhage in two patients, pulmonary embolism in four, ureteral fistula in three, and laparocele in three. The number of lymph nodes removed ranged from 30 to 117 with a median of 56. The mean lengths of vagina and lateral parametrium resected were 55 and 48 mm, respectively. Despite perioperative chemotherapy, lymph node metastasis was present in 36% of patients, parametrial disease in 38%, and vaginal disease in 45%. After a median follow-up of 53 months, the 5-year overall and disease-free survival rates of radically operated patients were 70% and 58%, respectively. CONCLUSIONS Thanks to improved surgical technique and perioperative care, extended radical surgery appears to be feasible with acceptable morbidity in chemosensitive women with Stage III cervical carcinoma and may constitute a valid alternative to radiotherapy in these patients. Cancer 1996;78:2359-65.

Serum levels of IL-6 were evaluated in a large group of patients with benign or malignant gynecological tumors. The results obtained were correlated with the patients' clinicopathological features and follow-up data. Using a highly sensitive immunoenzymatic method for the evaluation of serum IL-6 levels, we observed that > 5% of normal healthy women exhibited values within the range of 1.9-6 pg/ml. Using a cut-off of pg/ml, elevated levels of serum IL-6 were found in 53% of 45 patients with primary epithelial ovarian cancer and less frequently in patients with endometrial and cervical cancer (37% and 10% respectively). Elevated levels of IL-6 were occasionally seen in patients with benign disease. IL-6 serum levels appeared to be less sensitive than CA 125 in ovarian cancer diagnosis. In cancer patients, increased IL-6 serum levels were related to the presence of the tumor since all post-operative patients exhibited a marked decrease. In patients with advanced ovarian cancer post-operative levels of IL-6 correlated with residual disease. Very high levels of IL-6 were observed in the ascitic fluid of9 ovarian cancer patients, but IL-6 mRNA was not detected in tumor cells. This suggests that the increased production of IL-6 observed in ovarian cancer is reactive. Higher levels of IL-6 were found in patients unresponsive to chemotherapy, as compared with responsive ones. Univariate analysis of survival data suggests that increased IL-6 serum levels correlate with negative prognosis. © 1994 Wiley-Liss, Inc.

Two consecutive trials were conducted to evaluate a VHDCT programme with autologous bone marrow (ABM) or perlpheral stem cell (APSC) support in previously untreated OVCA patients (Pts) with macroscopic (0.5–2cm) residual tumor. Fifthy-one pts (median age 44; stage IIIC 78%) underwent: Induction chemotherapy (Indct) (2–4 cycles of a cisplatin and cyclophosphamide combination +/- G-CSF) with ABM and/or APSC hsrvestlng (H) foflowed by intensification (Int) CT (one course of a platinum, etoposide combination +/- L-PAM, +/-G-CSF&EPO) In the absence of clinical progression. 2nd-look laparotomy was performed in complete responders. 42 (82%) and 39 (76%) pts are evaluable for toxicity and pathological response (PR), respectively while 6 pts are still on treatment, 3 progressed when on treatment, 2 are awaiting 2nd look. One toxic death occurred due to systemic mycosis in a pt undergoing ABM transplantation (T). The number of leukaphereses required for adequate APSCH decreased after G-CSF Incorporation. Duration of BM aplasia progressively decressed lor pts receiving ABMT. APSCT and APSCT + G-cSF & EPO, respectively. 90% pR (CR 44%, PR 41% of which 36% microscopic) was revealed at 2nd-1ook. A median follow up of 28 (2–79) months has been reached from diagnosis. Only 2 of the 19 pathologically complete responders (6 with a > 5 year follow-up from 2nd-look) have so far relapsed without further therapy. Treatment proved to be feasible with acceptable toxicity when APSCT + G-CSF & EPO were used. The disease-free Interval would seem to be longer than expected in this pt subset. These data, if confirmed after a prolonged observation, warrants further investigation (in a randomized setting) on the possible therapeutic impact of this new approach on chemosensitive tumors.