Risk of SARS-CoV-2 infection and disease in metastatic triple-negative breast cancer patients treated with immune checkpoint inhibitors

Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease with particularly poor outcomes [1]. Over the past few years, relevant gains in knowledge concerning the molecular landscape of this disease have allowed to considerably broaden the available therapeutic armamentarium. Poly ADP-ribose polymerase-1 inhibitors, epigenetic agents, anti-androgens, tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs) may all optimally exemplify the targeted therapeutic weapons recently gained in the fight against mTNBC [2]. Targeting of immune checkpoints through their respective monoclonal antibodies translates into effective antitumor responses not only in widely recognized ‘immunogenic’ tumor types, for example, melanoma and renal cell carcinoma, but also in other solid tumors including breast cancer [3]. PD-1 is an immune checkpoint expressed on the surface of B cells, T cells and natural killer T cells, with a critical role in modulating self tolerance, immune homeostasis and inflammation. When activated by PD-L1 or -L2, PD-1 mediates downregulation of T-cell activity, causes T-cell lysis and reduces cytokine production significantl

The Association of Four Natural Molecules-EGCG, Folic Acid, Vitamin B12, and HA-To Counteract HPV Cervical Lesions: A Case Report

Precancerous lesions of the uterine cervix, due to HPV infections, are still today a great medical challenge. This clinical case highlighted the effectiveness of epigallocatechin gallate (EGCG), vitamin B12, folic acid, and hyaluronic acid (HA) in counteracting HPV lesions in a 39-year-old patient with a long history of viral persistence, cervical lesions of various degree, and several unsuccessful surgical approaches. After eight weeks of treatment, both the histological and cytological analyses revealed only a chronic cervicitis without any malignant lesions or cellular dysplasia, thus reducing the urgency of an invasive surgery, a total hysterectomy

Aqua Traiana, a Roman infrastructure embedded in the present: the mineralogical perspective

Construction materials from the internal ducts of Aqua Traiana, a still operative Roman aqueduct built in 109 AD to supply water to Rome, were characterized by optical microscopy (OM), scanning electron microscopy (SEM-EDS), X-ray powder diffraction (XRPD) and electron microprobe analysis (EMPA). Petrographic analysis and XRPD revealed that mortar aggregates are compatible with Vitruvius’ harena fossicia and allowed the distinction of the original mortars from those of the 17th-century papal restoration. The first showed an amorphous binder while the latter have a typical lime binder. By SEM-EDS and EMPA, the microstructure of mortar aggregates was analyzed and the composition of specific minerals quantified. Microanalysis testifies the Romans’ great expertise in the selection of pozzolanic building materials, giving evidence of the possible use of local tuffs from the Sabatini Volcanic District. It also confirms the exploitation of red pozzolan from the Roman Magmatic Province, specifically from the Alban Hills district. OM also proves a high compatibility with local supplies for bricks and cocciopesto. Of these, the first were fired at moderately low temperature, while the latter show an amorphous binder as in the original Trajan mortars. All building materials thus stand for similar technological choices and a coeval production

Malignant peritoneal mesothelioma in a woman with bilateral ovarian serous borderline tumour: Potential interactions between the two diseases

We report a case of a 59-year-old woman with peritoneal malignant mesothelioma and no previous exposure to asbestos with a diagnosis of bilateral ovarian serous borderline tumour with peritoneal implants one year before. We discuss the histopathological and immunohistochemical findings to explain possible and potential interactions between the two diseases. To our knowledge, the association of both serous borderline ovarian tumour and malignant peritoneal mesothelioma has never been described before in the same woman and in such a tight temporal connection. This finding raises numerous issues about the origin of the two tumours and further biomolecular studies are needed to fully understand the carcinogenetic process. From a clinical point of view, this case report can be useful to gynaecologists because it leads to recommend a careful examination of the peritoneal cavity during a surgical resection of borderline serous tumour. Moreover, it may suggest performing a close follow-up associated with a careful surveillance of the patient, especially in the case of micropapillary pattern, to oncologists. A complete clinical approach could help to detect sooner possible relapses or other metachronous malignancies

Recombinant activated protein C treatment improves tissue perfusion and oxygenation in septic patients measured by near-infrared spectroscopy

INTRODUCTION: The purpose was to test the hypothesis that muscle perfusion, oxygenation, and microvascular reactivity would improve in patients with severe sepsis or septic shock during treatment with recombinant activated protein C (rh-aPC) (n = 11) and to explore whether these parameters are related to macrohemodynamic indices, metabolic status or Sequential Organ Failure Assessment (SOFA) score. Patients with contraindications to rh-aPC were used as a control group (n = 5). MATERIALS AND METHODS: Patients were sedated, intubated, mechanically ventilated, and hemodynamically monitored with the PiCCO system. Tissue oxygen saturation (StO2) was measured using near-infrared spectroscopy (NIRS) during the vascular occlusion test (VOT). Baseline StO2 (StO2 baseline), rate of decrease in StO2 during VOT (StO2 downslope), and rate of increase in StO2 during the reperfusion phase were (StO2 upslope) determined. Data were collected before (T0), during (24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 96 hours (T1d)) and 6 hours after stopping rh-aPC treatment (T2) and at the same times in the controls. At every assessment, hemodynamic and metabolic parameters were registered and the SOFA score calculated. RESULTS: The mean +/- standard deviation Acute Physiology and Chronic Health Evaluation II score was 26.3 +/- 6.6 and 28.6 +/- 5.3 in rh-aPC and control groups, respectively. There were no significant differences in macrohemodynamic parameters between the groups at all the time points. In the rh-aPC group, base excess was corrected (P < 0.01) from T1a until T2, and blood lactate was significantly decreased at T1d and T2 (2.8 +/- 1.3 vs. 1.9 +/- 0.7 mmol/l; P < 0.05). In the control group, base excess was significantly corrected at T1a, T1b, T1c, and T2 (P < 0.05). The SOFA score was significantly lower in the rh-aPC group compared with the controls at T2 (7.9 +/- 2.2 vs. 12.2 +/- 3.2; P < 0.05). There were no differences between groups in StO2 baseline. StO2 downslope in the rh-aPC group decreased significantly at all the time points, and at T1b and T2 (-16.5 +/- 11.8 vs. -8.1 +/- 2.4%/minute) was significantly steeper than in the control group. StO2 upslope increased and was higher than in the control group at T1c, T1d and T2 (101.1 +/- 62.1 vs. 54.5 +/- 23.8%/minute) (P < 0.05). CONCLUSIONS: Treatment with rh-aPC may improve muscle oxygenation (StO2 baseline) and reperfusion (StO2 upslope) and, furthermore, rh-aPC treatment may increase tissue metabolism (StO2 downslope). NIRS is a simple, real-time, non-invasive technique that could be used to monitor the effects of rh-aPC therapy at microcirculatory level in septic patient

Fasting glucose and body mass index as predictors of activity in breast cancer patients treated with everolimus-exemestane: the EverExt study

Evidence on everolimus in breast cancer has placed hyperglycemia among the most common high grade adverse events. Anthropometrics and biomarkers of glucose metabolism were investigated in a observational study of 102 postmenopausal, HR + HER2- metastatic breast cancer patients treated with everolimus-exemestane in first and subsequent lines. Best overall response (BR) and clinical benefit rate (CBR) were assessed across subgroups defined upon fasting glucose (FG) and body mass index (BMI). Survival was estimated by Kaplan-Meier method and log-rank test. Survival predictors were tested in Cox models. Median follow up was 12.4 months (1.0-41.0). The overall cohort showed increasing levels of FG and decreasing BMI (p &lt; 0.001). Lower FG fasting glucose at BR was more commonly associated with C/PR or SD compared with PD (p &lt; 0.001). We also observed a somewhat higher BMI associated with better response (p = 0.052). More patients in the lowest FG category achieved clinical benefit compared to the highest (p &lt; 0.001), while no relevant differences emerged for BMI. Fasting glucose at re-assessment was also predictive of PFS (p = 0.037), as confirmed in models including BMI and line of therapy (p = 0.049). Treatment discontinuation was significantly associated with changes in FG (p = 0.014). Further research is warranted to corroborate these findings and clarify the underlying mechanisms

MRI of placenta accreta: diagnostic accuracy and impact of interventional radiology on foetal-maternal delivery outcomes in high-risk women

To assess accuracy and reproducibility of MRI diagnosis of invasive placentation (IP) in high-risk patients and to evaluate reliability of MRI features. Secondary aim was to evaluate impact of interventional radiology (IR) on delivery outcomes in patients with IP at MRI

Role of evaluating tumor‑infiltrating lymphocytes, programmed death‑1 ligand 1 and mismatch repair proteins expression in malignant mesothelioma

The tumor immune microenvironment (TME) and immune checkpoints have been reported to serve a role in the pathogenesis of malignant mesothelioma (MM) and treatment outcome. Additionally, mismatch Repair (MMR) deficiency appears to enhance the response to checkpoints blockade in several tumors. The aim of the present study was to analyze programmed death‑1 ligand 1 (PD‑L1) expression in MM and to characterize the TME. This could help to understand the immune response, and evaluate its prognostic and predictive values. We also investigated MMR protein expression. We retrospectively analyzed 55 mesotheliomas to determine PD‑L1, CD4+, CD8+, mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6) and PMS1 homolog 2, mismatch repair system component (PMS2) expression. We used an immunoscore (1+, 2+ and 3+) to evaluate tumor‑infiltrating lymphocytes (TILs). TILs were observed in all but two samples (53/55); the majority had an immunoscore 1+ (30/53), while 2+/3+ was reported for 23/53 samples. A predominance of CD8+ was highlighted in 8 cases (15%). PD‑L1 expression of ≥1% on tumor cells was displayed in 40 cases; in 9 of these, ≥50% expression was reported. Of note, alterations in MMR staining was not observed. In addition, survival analysis revealed that epithelioid subtype was associated with better prognosis. We observed a trend towards poorer prognosis for ≥50% PD‑L1 expression on tumor cells, lower immunoscore (1+) and CD8+ TIL predominance. The present study highlighted the importance of exploring the TME and the standardization of PD‑L1 assessment guidelines to apply in the field of immunotherapy

How microanalysis can be discriminant on black Pompeian wares

In the present work the advantages of punctual approaches are discussed in the discrimination of black wares from the Sanctuary of Venus Fisica (Pompeii, Italy), dated between the 2nd and 1st century BC. Black-gloss ware and "bucchero" samples are analyzed by a multi-analytical approach including optical microscopy (OM), X-ray powder diffraction (XRPD), scanning electron microscopy with Energy Dispersive Spectroscopy (SEM-EDS) and electron microprobe analysis (EMPA) to investigate the mineralogical and petrographic features of these artefacts. Grain size, firing conditions and potter’s expertise influenced the final appearance of the superficial decorative black layer. In addition, punctual chemical analysis was fundamental to verify the archaeological indication of specific production sites

Effects of vasopressinergic receptor agonists on sublingual microcirculation in norepinephrine-dependent septic shock.

none15ABSTRACT: INTRODUCTION: The present study was designed to determine the effects of continuously infused norepinephrine (NE) plus (1) terlipressin (TP) or (2) arginine vasopressin (AVP) or (3) placebo on sublingual microcirculation in septic shock patients. The primary study end point was a difference of ≥ 20\% in the microvascular flow index of small vessels among groups. METHODS: The design of the study was a prospective, randomized, double-blind clinical trial. NE was titrated to maintain mean arterial pressure (MAP) between 65 and 75 mmHg after establishment of normovolemia in 60 septic shock patients. Thereafter patients (n = 20 per group) were randomized to receive continuous infusions of either TP (1 μg/kg/hour), AVP (0.04 U/minute) or placebo (isotonic saline). In all groups, open-label NE was adjusted to maintain MAP within threshold values if needed. The sublingual microcirculatory blood flow of small vessels was assessed by sidestream dark-field imaging. All measurements, including data from right heart catheterization and norepinephrine requirements, were obtained at baseline and 6 hours after randomization. RESULTS: TP and AVP decreased NE requirements at the end of the 6-hour study period. The data are medians (25th and 75th interquartile ranges (IQRs)): 0.57 μg/kg/minute (0.29 to 1.04) vs. 0.16 μg/kg/minute (0.03 to 0.37) for TP and 0.40 μg/kg/minute (0.20 to 1.05) vs. 0.23 μg/kg/minute (0.03 to 0.77) for AVP, with statistical significance of P < 0.05 vs. baseline and vs. placebo. There were no differences in sublingual microcirculatory variables, systemic hemodynamics, oxygen transport and acid-base homeostasis among the three study groups during the entire observation period. The proportions of perfused vessels increased in relation to baseline within all study groups, and there were no significant differences between groups. The specific data were as follows (median (IQR)): 9.7\% (2.6 to 19.8) for TP, 8.9\% (0.0 to 17.8) for AVP, and 6.9\% (3.5 to 10.1) for placebo (P < 0.05 vs. baseline for each comparison), as well as perfused vessel density 18.6\% (8.6 to 36.9) for TP, 20.2\% (-3.0 to 37.2) for AVP, and 11.4\% (-3.0 to 19.4) for placebo (P < 0.05 vs. baseline for each comparison). CONCLUSIONS: The present study suggests that to achieve a MAP of 65 to 75 mmHg in septic patients treated with NE, the addition of continuously infused low-dose TP or AVP does not affect sublingual microcirculatory blood flow. In addition, our results suggest that microcirculatory flow abnormalities are mainly related to other factors (for example, volume status, timing, hemodynamics and progression of the disease) rather than to the vasopressor per se. TRIAL REGISTRATION: ClinicalTrial.gov NCT00995839.A. Morelli;A. Donati;C. Ertmer;S. Rehberg;T. Kampmeier;A. Orecchioni;A. D. Russo;A. D'Egidio;G. Landoni;M. R. Lombrano;L. Botticelli;A. Valentini;A. Zangrillo;P. Pietropaoli;M. WestphalA., Morelli; Donati, Abele; C., Ertmer; S., Rehberg; T., Kampmeier; A., Orecchioni; A. D., Russo; A., D'Egidio; G., Landoni; M. R., Lombrano; L., Botticelli; A., Valentini; A., Zangrillo; P., Pietropaoli; M., Westpha