Methodological and reporting standards for quality-of-life data eligible for European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) credit.

BACKGROUND: The European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS) has been developed to grade clinical benefit of cancer therapies. Improvement in quality of life (QoL) is considered relevant, especially in the non-curative setting. This is reflected by an upgrade of the preliminary ESMO-MCBS score if QoL is improved compared to the control arm or a downgrade if an improvement in progression-free survival is not paralleled by an improvement in QoL or overall survival. Given the importance of QoL for the final score, a need to ensure the robustness of QoL data was recognised. DESIGN: A checklist was created based on existing guidelines for QoL research. Field testing was carried out using clinical trials that either received an adjustment of the preliminary ESMO-MCBS score based on QoL or had QoL as the primary endpoint. Several rounds of revision and re-testing of the checklist were undertaken until a final consensus was reached. RESULTS: The final checklist consists of four items and can be applied if three prerequisites are met: (i) QoL is at least a secondary endpoint, (ii) evidence of reliability and validity of the instrument is provided, and (iii) a statistically and clinically significant improvement in QoL is observed. The four items on the checklist pertain to the (i) hypothesis, (ii) compliance and missing data, (iii) presentation of the results, and (iv) statistical and clinical relevance. Field testing revealed that a clear QoL hypothesis and correction for multiple testing were mostly lacking, while the main statistical method was always described. CONCLUSIONS: Implementation of the ESMO-MCBS QoL checklist will facilitate objective and transparent decision making on QoL data within the ESMO-MCBS scoring process. Trials published until 1 January 2025 will have to meet the prerequisites and at least two items for crediting QoL benefit in the final ESMO-MCBS score. Trials published thereafter will have to meet all four items.

The size, shape, density and ring of the dwarf planet Haumea from a stellar occultation.

Haumea-one of the four known trans-Neptunian dwarf planets-is a very elongated and rapidly rotating body. In contrast to other dwarf planets, its size, shape, albedo and density are not well constrained. The Centaur Chariklo was the first body other than a giant planet known to have a ring system, and the Centaur Chiron was later found to possess something similar to Chariklo's rings. Here we report observations from multiple Earth-based observatories of Haumea passing in front of a distant star (a multi-chord stellar occultation). Secondary events observed around the main body of Haumea are consistent with the presence of a ring with an opacity of 0.5, width of 70 kilometres and radius of about 2,287 kilometres. The ring is coplanar with both Haumea's equator and the orbit of its satellite Hi'iaka. The radius of the ring places it close to the 3:1 mean-motion resonance with Haumea's spin period-that is, Haumea rotates three times on its axis in the time that a ring particle completes one revolution. The occultation by the main body provides an instantaneous elliptical projected shape with axes of about 1,704 kilometres and 1,138 kilometres. Combined with rotational light curves, the occultation constrains the three-dimensional orientation of Haumea and its triaxial shape, which is inconsistent with a homogeneous body in hydrostatic equilibrium. Haumea's largest axis is at least 2,322 kilometres, larger than previously thought, implying an upper limit for its density of 1,885 kilograms per cubic metre and a geometric albedo of 0.51, both smaller than previous estimates. In addition, this estimate of the density of Haumea is closer to that of Pluto than are previous estimates, in line with expectations. No global nitrogen- or methane-dominated atmosphere was detected.

Using rADioMIcs and machine learning with ultrasonography for the differential diagnosis of myometRiAL tumors (the ADMIRAL pilot study). Radiomics and differential diagnosis of myometrial tumors.

OBJECTIVE: To develop and evaluate the performance of a radiomics and machine learning model applied to ultrasound (US) images in predicting the risk of malignancy of a uterine mesenchymal lesion. METHODS: Single-center retrospective evaluation of consecutive patients who underwent surgery for a malignant uterine mesenchymal lesion (sarcoma) and a control group of patients operated on for a benign uterine mesenchymal lesion (myoma). Radiomics was applied to US preoperative images according to the International Biomarker Standardization Initiative guidelines to create, validate and test a classification model for the differential diagnosis of myometrial tumors. The TRACE4 radiomic platform was used thus obtaining a full-automatic radiomic workflow. Definitive histology was considered as gold standard. Accuracy, sensitivity, specificity, AUC and standard deviation of the created classification model were defined. RESULTS: A total of 70 women with uterine mesenchymal lesions were recruited (20 with histological diagnosis of sarcoma and 50 myomas). Three hundred and nineteen radiomics IBSI-compliant features were extracted and 308 radiomics features were found stable. Different machine learning classifiers were created and the best classification system showed Accuracy 0.85 ± 0.01, Sensitivity 0.80 ± 0.01, Specificity 0.87 ± 0.01, AUC 0.86 ± 0.03. CONCLUSIONS: Radiomics applied to US images shows a great potential in differential diagnosis of mesenchymal tumors, thus representing an interesting decision support tool for the gynecologist oncologist in an area often characterized by uncertainty.

Reducing energy demand by the combined application of advanced control strategies in a full scale WWTP.

Two advanced control strategies were applied in the secondary and tertiary stages, respectively, of a full scale wastewater treatment plant (WWTP). This has a nominal capacity of 330,000 population equivalent (PE), a complex configuration (having been upgraded several times through the years), and it faces significant seasonal load fluctuations (being located in a touristic area, in Northern Italy). The lifting station of the tertiary treatments (devoted to phosphorus precipitation and UV disinfection) was optimized by adjusting the pumped flowrate, depending on influent phosphorus concentration. A preliminary simulation showed that a 15% reduction of pumping energy could be achieved. This result was confirmed by field measurements. Moreover, a fuzzy control system was designed and applied to one of the six parallel nitrification reactors, yielding a reduction of more than 25% of the power requirement for aeration. Overall, the combined application of the two controllers led to a 7% reduction of the total energy consumption of the plant. This result is particularly promising given that the fuzzy controller was applied only to one of six biological reactors.

Comparison between intrarticular injection of hyaluronic acid, oxygen ozone, and the combination of both in the treatment of knee osteoarthrosis.

This study aimed to compare short-term clinical outcomes between intra-articular injection of hyaluronic acid (HA), oxygen ozone (O2O3), and the combination of both, in patients affected by osteoarthrosis (OA) of the knee. Seventy patients (age 45-75 years) with knee OA were randomized to intra-articular injections of HA (n=23), or O2O3 (n=23) or combined (n=24) one per week for 5 consecutive weeks. KOOS questionnaire and visual analog scale (VAS), before treatment (pre) at the end (post), and at 2 months after treatment ended (follow-up) were used as outcome measures. Analysis showed a significant effect (P < 0.05) of the conditions (pre, post and follow-up) in all parameters of the KOOS score and a significant effect (P < 0.05) of groups (HA, O2O3 and combined) for pain, symptoms, activities of daily living and quality of life. The combined group scores were higher compared to the HA and O2O3 groups, especially at follow-up. The combination of O2O3 and HA treatment led to a significantly better outcome especially at 2-month follow-up compared to HA and O2O3 given separately to patients affected by OA of the knee.

Acute longitudinal myelitis following Cryptococcus laurentii pneumonia in a patient with systemic lupus erythematosus.

Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) is reported in about 50% of patients. Among the neuropsychiatric features of SLE, myelopathy, including acute transverse myelitis (ATM) or acute longitudinal myelitis (ALM), represents an uncommon event. A possible vascular aetiology of SLE myelopathies has been hypothesized and it seems to be much more associated to SLE-associated antiphospholipid syndrome (APS). Furthermore, a possible infectious cause of ATM or ALM in healthy subjects has been described. SLE patients are susceptible to infection due to the disease itself or to the immunosuppressive therapy. Cryptococci non-neoformans have been rarely associated to infections in humans. Here we describe the case of a 47-year-old woman with SLE and Sjögren Syndrome who developed an ALM concurrently with a Cryptococcus laurentii pneumonia. The patient was treated with antimycotics, high doses of glucocorticoids and intravenous immunoglobulins with a significant clinical and radiological improvement. As far as we know, this is the first case of Cryptococcus laurentii infection and ALM in a patient with SLE who later developed a seronegative APS. Even though myelopathy may be considered primarily associated to SLE, a possible role of the infection in ALM development cannot be excluded.

Response to treatment and prognostic significance of supradiaphragmatic disease in patients with high-grade serous ovarian cancer.

OBJECTIVES: This study was designed to investigate the response to chemotherapy of supradiaphragmatic disease diagnosed by preoperative imaging. As secondary objectives, oncologic outcomes of patients affected by supradiaphragmatic disease and their pattern of recurrence were also evaluated. METHODS: Data of consecutive patients with newly diagnosed FIGO stage IV (for supradiaphragmatic disease) epithelial ovarian cancer undergoing either primary debulking surgery or neoadjuvant chemotherapy plus interval debulking surgery between 2004 and 2021, were retrospectively collected. All patients were preoperatively evaluated by chest/abdominal CT scan or 18F-FDG PET/CT preoperatively and at follow-up to evaluate response to chemotherapy. At follow-up visits, site of recurrence diagnosed by imaging techniques was systematically recorded as it occurred. Progression-free and overall survival were measured by using Kaplan-Meier and Cox models. RESULTS: A total of 130 patients was included in this study with a median (range) follow-up of 32.9 (12.8-176.7) months. Complete or partial response was achieved in most of the patients after 3 cycles (77.7%) and 6 cycles (85.4%) of chemotherapy. At follow-up, recurrence occurred in 96 (73.8%) patients and the main site of recurrence was abdomen only in 64 (66.7%) patients. At multivariate analysis, residual disease after surgery was the only variable influencing survival outcomes. CONCLUSIONS: Supradiaphragmatic disease respond to chemotherapy in most patients affected by advanced EOC and recurrence mainly occurs in the abdomen. Results from this study confirms that abdominal optimal cytoreduction is the main surgical goal in the treatment of women affected by FIGO stage IV EOC.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Early detection of second breast cancers improves prognosis in breast cancer survivors.

BACKGROUND: The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase. PATIENTS AND METHODS: Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias. RESULTS: Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73. CONCLUSION: Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.

Automatic classification of electroencephalograms: Kullback-Leibler nearest neighbor rules.

A prototypic problem in screening of electroencephalograms in the automatic classification of stationary electroencephalogram time series is treated here by the Kullback-Leibler nearest neighbor rule approach. In that problem, the category or state of an individual is classified by comparison of his or her electroencephalogram with those taken from other individuals in the alternative categories. The Kullback-Leibler nearest neighbor classification rules yield a statistically reliable estimate of the smallest possible probability of electroencephalogram misclassification with a relatively small number of labeled sample electroencephalograms. The automatic classification of anesthesia levels L1 and L3, respectively the anesthesia levels insufficient and sufficient for deep surgery, is treated by machine computation on the electroencephalogram alone.

[Renal involvement in Fabry's disease: diagnosis, follow-up and enzyme replacement therapy]. / La nefropatia in corso di malattia di Fabry: diagnosi, follow-up e terapia enzimatica sostitutiva.

Renal involvement in Fabry's disease in males starts at an early age with microalbuminuria and proteinuria and progresses rapidly towards end-stage renal disease requiring dialysis or renal transplantation. Renal involvement, together with cardiac and cerebral damage, is responsible for the severe morbidity and mortality in patients with Fabry's disease. In heterozygous female patients renal involvement has also been documented, but the onset of renal damage occurs later and the progression to end-stage renal disease is slower. Considering the relevance of renal damage in the prognosis of Fabry's disease, it is mandatory to point out the diagnostic criteria of Fabry's nephropathy and the modalities of follow-up of patients with renal involvement. The aim of this study is also to provide recommendations regarding the diagnosis, follow-up and indication for enzyme replacement therapy in patients with Fabry's disease.

Second breast cancers in a Tuscan case series: characteristics, prognosis, and predictors of survival.

Little is known about long-term outcomes following a second breast cancer diagnosis. We describe the epidemiology, characteristics and prognosis of second breast cancers in an Italian cohort. We identified women with two breast cancer diagnoses from 24 278 histology records at a Tuscan breast cancer service between 1980 and 2005, and determined their survival status. Disease-specific survival from second diagnosis was examined using Cox regression analyses. Second cancers were identified in 1044 women with a median age of 60 years. In all 455 were ipsilateral relapses and 589 were contralateral cancers. Median time between first and second diagnosis was 63.4 months. The majority of second cancers was small invasive or in situ tumours. Estimated 10-year survival from a second cancer diagnosis was 78%. Survival was poorest when the second cancer was large (HR=2.26) or node-positive (HR=3.43), when the time between the two diagnoses was <5 years (HR=1.45), or when the diagnosis was in an earlier epoch (HR=2.20). Second tumours were more likely to be large or node-positive if the first breast cancer had these features. Prognosis following a second breast cancer in this cohort was generally good. However, large or node-positive second tumours, and shorter intervals between diagnoses were indicators of poorer survival.

PSA doubling time as a predictor of the outcome of random prostate biopsies prompted by isolated PSA elevation in subjects referred to an outpatient biopsy facility in a routine clinical scenario.

AIM: To assess the validity of PSA doubling time (PSADT) as a predictor of prostate sextant biopsy outcome in patients with PSA levels in the 4-10 ng/mL range. MATERIAL AND METHODS: A consecutive series of 355 sextant biopsies performed during 2001-2007 in subjects with negative digital rectal examination and transrectal ultrasonography was considered. Variables tested as possible predictors were age, total and free/total PSA value, PSA velocity and PSA doubling time. While PSA at time of biopsy and free/total PSA were determined with a standardized method undergoing strict quality control, previous PSA values used to assess velocity/doubling time came from other labs using different assays over widely varying intervals of time. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. RESULTS: Apart from free/total PSA ratio, no other studied variable showed a statistically significant and independent association with biopsy outcome, either at univariate or multivariate analysis. No studied variable had a good performance as a biopsy indicator. Depending on the variable considered, 1.17 to 1.97 cancers would be missed to spare 10 benign biopsies. CONCLUSION: When based on PSA data determined with different assays over widely varying intervals and in the absence of an underlying protocol for PSA surveillance, PSA velocity and doubling time should never discount a biopsy prompted by total PSA elevation.

Mammaglobin B expression in human endometrial cancer.

Mammaglobin B (MGB-2) is an uteroglobin gene family member recently found highly differentially expressed in ovarian cancer by gene expression profiling. To evaluate its potential as a novel endometrial cancer biomarker, in this study we quantified and compared MGB-2 expression at messenger RNA and protein levels in endometrial tumors (endometrioid endometrial cancer [EEC]) with different grades of differentiation. MGB-2 expression was evaluated by real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) in fresh frozen biopsies and paraffin-embedded tissues derived from a total of 70 patients including 50 primary EEC and 20 normal endometria (NECs). High levels of MGB-2 gene expression were detected in 10 of 11 EEC G1 cases (91%), 16 of 17 EEC G2 cases (94%), and 6 of 22 EEC G3 cases (27%) by real-time PCR. In contrast, normal endometrial cells expressed low to negligible levels of MGB-2 by real-time PCR (P = 0.002 EEC vs NEC). Well- and moderately differentiated EECs overexpressed MGB-2 gene at significant higher levels when compared to NECs (P < 0.01). Pairwise differences between both G2 and G1 vs G3 cases for MGB-2 relative gene expression values were also statistically significant (G2 vs G3 P < 0.001, G1 vs G3 P = 0.016). MGB-2 protein expression was detected in 31 (86%) of 36 EEC and 0 of 5 atrophic NEC controls, while seven of eight (88%) of the proliferative/secretory/hyperplastic NECs focally expressed MGB-2 by IHC. MGB-2 is highly expressed in EEC, particularly in well- and moderately differentiated tumors, and may represent a novel molecular marker for EEC.

Is aortic lymphadenectomy indicated in locally advanced cervical cancer after neoadjuvant chemotherapy followed by radical surgery? A retrospective study on 261 women.

OBJECTIVES: The aim of this study was to estimate the rate of aortic lymph nodes (LN) metastases/recurrences among patients affected by locally advanced stage cancer patients (LACC), treated with neoadjuvant chemotherapy (NACT) and radical surgery. METHODS: Retrospective evaluation of consecutive 261 patients affected by LACC (stage IB2-IIB), treated with NACT followed by radical surgery at National Cancer Institute, Milan, Italy, between 1990 and 2011. RESULTS: Stage at presentation included stage IB2, IIA and IIB in 100 (38.3%), 50 (19.2%) and 111 (42.5%) patients, respectively. Squamous cell carcinoma accounted for more than 80%, followed by adenocarcinoma or adenosquamous cancers (20%). Overall, 56 women (21.5%) had LN metastases. Four out of 83 women (5%) who underwent both pelvic and aortic LN dissection had aortic LN metastases, and all women had concomitant pelvic and aortic LN metastases. Only one woman out of 178 (0.5%) who underwent pelvic lymphadenectomy only, had an aortic LN recurrence. Overall 2% of women (5/261) had aortic LN metastases/recurrence. CONCLUSIONS: Our data suggest that aortic lymphadenectomy at the time of surgery is not routinely indicated in LACC after NACT, but should reserved in case of bulky LN in both pelvic and/or aortic area. The risk of isolated aortic LN relapse is negligible. Further prospective studies are warranted.

Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the 'Florence' diet is not Mediterranean.

OBJECTIVE: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels. DESIGN: Cross-sectional. SETTING: Population-based study. SUBJECTS: A sample of 520 clinically healthy subjects (211 males, 309 females) with a mean age of 46 y, living in Florence area, Italy. INTERVENTIONS: Dietary pattern was assessed by trained dietitians through a semiquantitative food questionnaire. Fasting blood samples were drawn for assessment of lipid profile, homocysteine and circulating vitamins. RESULTS: Contribution from total fats was over 30% in about 70% of subjects and intake of saturated fatty acids (SFA) was above the recommended values in at least 40% of the study population. Furthermore, almost the whole (99.6%) population reported low intake of polyunsaturated fatty acids (PUFA). High levels of total cholesterol were present in over 40% of the study population, whereas abnormal values of LDL-cholesterol were observed in about 30%. High levels of homocysteine were found in 11.7% of the study population. An extremely high percentage of subjects reported low intake of vitamins, especially with regard to folic acid (89%), vitamin B(6) (70.1%) and vitamin E (99.6%). In a multiple linear regression model, circulating levels of vitamin B(12) and folic acid, and intake of alcohol and vitamin C resulted in being independently associated with homocysteine plasma levels. CONCLUSIONS: In a typical Mediterranean country, general outlines of Mediterranean diet are not completely followed, especially concerning total fats, SFA, PUFA and vitamins' intake. SPONSORSHIP: Ministero della Salute (Italy) - 'Progetto per la Salute e la Prevenzione di Malattia' 2001-2003.

Heart rate variability in athletes and nonathletes at rest and during head-up tilt.

The purpose of the present study was to determine if autonomic heart rate modulation, indicated by heart rate variability (HRV), differs during supine rest and head-up tilt (HUT) when sedentary and endurance-trained cyclists are compared. Eleven sedentary young men (S) and 10 trained cyclists (C) were studied. The volunteers were submitted to a dynamic ECG Holter to calculate HRV at rest and during a 70 masculine HUT. The major aerobic capacity of athletes was expressed by higher values of VO2 at anaerobic threshold and peak conditions (P < 0.05). At rest the athletes had lower heart rates (P < 0.05) and higher values in the time domain of HRV compared with controls (SD of normal RR interval, SDNN, medians): 59.1 ms (S) vs 89.9 ms (C), P < 0.05. During tilt athletes also had higher values in the time domain of HRV compared with controls (SDNN, medians): 55.7 ms (S) vs 69.7 ms (C), P < 0.05. No differences in power spectral components of HRV at rest or during HUT were detected between groups. Based on the analysis of data by the frequency domain method, we conclude that in athletes the resting bradycardia seems to be much more related to changes in intrinsic mechanisms than to modifications in autonomic control. Also, HUT caused comparable changes in sympathetic and parasympathetic modulation of the sinus node in both groups.

How often parametrial involvement leads to post-operative adjuvant treatment in locally advanced cervical cancer after neoadjuvant chemotherapy and type C radical hysterectomy?

OBJECTIVE: Parametrial involvement (PMI) is one of the most important factors influencing prognosis in locally advanced stage cervical cancer (LACC) patients. We aimed to evaluate PMI rate among LACC patients undergoing neoadjuvant chemotherapy (NACT), thus evaluating the utility of parametrectomy in tailor adjuvant treatments. METHODS: Retrospective evaluation of consecutive 275 patients affected by LACC (IB2-IIB), undergoing NACT followed by type C/class III radical hysterectomy. Basic descriptive statistics, univariate and multivariate analyses were applied in order to identify factors predicting PMI. Survival outcomes were assessed using Kaplan-Meier and Cox models. RESULTS: PMI was detected in 37 (13%) patients: it was associated with vaginal involvement, lymph node positivity and both in 10 (4%), 5 (2%) and 12 (4%) patients, respectively; while PMI alone was observed in only 10 (4%) patients. Among this latter group, adjuvant treatment was delivered in 3 (1%) patients on the basis of pure PMI; while the remaining patients had other characteristics driving adjuvant treatment. Considering factors predicting PMI we observed that only suboptimal pathological responses (OR: 1.11; 95% CI: 1.01, 1.22) and vaginal involvement (OR: 1.29 (95%) CI: 1.17, 1.44) were independently associated with PMI. PMI did not correlate with survival (HR: 2.0; 95% CI: 0.82, 4.89); while clinical response to NACT (HR: 3.35; 95% CI: 1.59, 7.04), vaginal involvement (HR: 2.38; 95% CI: 1.12, 5.02) and lymph nodes positivity (HR: 3.47; 95% CI: 1.62, 7.41), independently correlated with worse survival outcomes. CONCLUSIONS: Our data suggest that PMI had a limited role on the choice to administer adjuvant treatment, thus supporting the potential embrace of less radical surgery in LACC patients undergoing NACT. Further prospective studies are warranted.

HIV p17 enhances lymphocyte proliferation and HIV-1 replication after binding to a human serum factor.

OBJECTIVE: To analyse the role of recombinant HIV-1 protein p17 in the modulation of cell activity. METHODS: Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the presence or absence of p17 with mitogens such as phytohaemagglutinin or interleukin-2 and their response assayed by cell proliferation. Cross-linking experiments were employed to investigate the presence of a binding between p17 and factor(s) present in human serum. An immunoenzymatic assay for p24 antigen detection was used to analyse the effect of the addition of exogenous p17 to cultures of PBMC infected with HIV-1 in vitro. RESULTS: Purified recombinant p17 protein at a concentration of 0.25 microg/ml significantly increased the proliferation of preactivated PBMC obtained from healthy donors. This effect was obtained by binding p17 to factor(s) present in human serum and observed on both CD4+ and CD8+ T cells. Recombinant p17 also induced an increased rate of HIV-1 replication, probably due to enhanced T-cell proliferation. The activity of p17 protein was inhibited by anti-p17 antibodies generated by injecting recombinant p17 in rabbits, but not by human antibodies generated during the natural course of HIV infection. CONCLUSION: Characterization of the human factor(s) and identification of the interacting p17 epitope(s) will improve our understanding of the mechanisms used by HIV to efficiently replicate in our organisms.