Molecular Interactions and Mechanisms of COVID-19 Inhibition 2.0.

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BRCA Testing for Patients Treated in Italy: A National Survey of Breast Centers Associated with Senonetwork.

BACKGROUND: Breast units (BUs) provide breast cancer (BC) care, including prevention, treatment, and genetic assessment. Genetic research has highlighted BRCA1/2 mutations as key hereditary BC risk factors. BRCA testing is crucial for personalized treatment and prevention strategies. However, the integration of BRCA testing in Italian BUs faces multiple challenges. This study, by Senonetwork Italia, aimed to evaluate genetic testing practices and identify obstacles within Italian BUs. METHODS: Senonetwork Italia conducted a 16-question web-based survey involving 153 BUs. The survey assessed aspects of BRCA testing, including timing, urgency, counseling, patient selection, and multi-gene panels. RESULTS: Of the 153 BUs, 109 (71.2%) responded. Testing before surgery was performed by 70.6% of centers, with urgent cases acknowledged by 87.2%. Most centers (56.0%) arranged urgent pre-test counseling within a week. BRCA mutation status influenced treatment decisions in 99.1% of cases. Multi-gene panels were used by 33.0% of centers for all genetic counseling cases, while 56.0% followed standard referral criteria. The main challenges included cost, reimbursement, and reporting timelines. CONCLUSIONS: This survey highlights significant variations in BRCA testing practices across Italian BUs and identifies key logistical and financial challenges. There is a need for standardized practices of genetic testing to ensure personalized and effective BC management in Italy.

Breakthrough Acute HIV Infections among Pre-Exposure Prophylaxis Users with High Adherence: A Narrative Review.

Pre-exposure prophylaxis (PrEP) is a pivotal intervention among HIV prevention strategies. We aimed to narratively revise the topic of HIV acute infection in the setting of PrEP exposure with a focus on diagnostic options, clinical features, and future PrEP perspectives, with a particular focus on users with high adherence to PrEP. We searched the main databases (PubMed, Embase, and Scopus) with the keywords "PrEP" or "Pre-Exposure Prophylaxis" and "HIV" or "PLWH" and "breakthrough" or "acute infection" or "primary infection". We included all randomized clinical trials and non-experimental studies (both case reports and observational studies) ever published. In the present narrative review, we revise the diagnostic challenges related to HIV diagnosis in the setting of PrEP and the clinical characteristics and symptoms of breakthrough infections. We discuss the management of acute HIV infection during PrEP and the new challenges that arise from the use of long-acting drugs for PrEP. Our review underlines that although extremely rare, HIV seroconversions are still possible during PrEP, even in a context of high adherence. Efforts to promptly identify these events must be included in the PrEP follow-up in order to minimize the chance of overlooked HIV breakthrough infections and thus exposure to suboptimal concentrations of antiretrovirals.

Third national surgical consensus conference of the Italian Association of Breast Surgeons (ANISC) on management after neoadjuvant chemotherapy: The difficulty in reaching a consensus.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) has a profound impact on surgical management of breast cancer. For this reason, the Italian Association of Breast Surgeons (ANISC) promoted the third national Consensus Conference on this subject, open to multidisciplinary specialists. MATERIALS AND METHODS: The Consensus Conference was held on-line in November 2022, and after an introductory session with five core-team experts, participants were asked to vote on eleven controversial issues, while results were collected in real-time with a polling system. RESULTS: A total of 164 dedicated specialists from 74 Breast Centers participated. Consensus was reached for only three of the eleven issues, including: 1) the indication to assess the response with Magnetic Resonance Imaging (79 %); 2) the need to re-assess the biological factors of the residual tumor if present (96 %); 3) the possibility of omitting a formal axillary node dissection for cN1 patients if a pathologic Complete Response (pCR) was confirmed with analysis of one or more sentinel lymph nodes (82 %). The majority voted in favor of mapping both the breast and nodal lesions pre-NAC (59 %), and against the omission of sentinel lymph node biopsy in cN0 patients in the case of pathologic or clinical Complete Response (69 %). In cases of cT3/cN1+ tumors with pCR, only 8 % of participants considered appropriate the omission of Post-Mastectomy Radiation Therapy. CONCLUSION: There is still a wide variability in surgical approaches after NAC in the "real world". As NAC is increasingly used, multidisciplinary teams should be attuned to conforming their procedures to the rapid advances in this field.

Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

Easy Anthropometric Measurements Are Representative of Baseline Values of Breast Q Values in Asymptomatic Women.

BACKGROUND: Measurements of breast morphology are a determinant of the assessment of any surgical procedure, either reconstructive or cosmetic. This study aims to investigate the association between easy anthropometric measurements and values of quality of life assessed in a sample of asymptomatic women. METHODOLOGY: Healthy asymptomatic women were admitted for this study. The following measurements were assessed: height, weight, nipple to sternal notch distance, areola to infra-mammary fold distance (right vs. left), right-left nipple distance. The Breast Q questionnaire (Italian translation V.1, pre-op breast conservation surgery) in the following domains: satisfaction with breasts; psycho-social satisfaction; physical satisfaction; sexual satisfaction, which was used to assess breast-related quality of life. RESULTS: One hundred and forty-five women responded to the breast Q questionnaire. The mean age of the sample was 44.3 years; the medium BMI was 24.1; Spearman correlation coefficients revealed that all the investigated values were negatively correlated to the "satisfaction with breasts" domain. Psychosexual satisfaction was associated with age; BMI; nipple to sternal notch distance. After normalization for age values, we observed that "satisfaction with breast" was, once again, highly correlated to BMI; nipple to sternal notch distance; areola to IMF distance. In all cases, the higher the values, the lower the scores. CONCLUSIONS: Distances between easy relevant anatomical landmarks are representative of patients' breast-related quality of life in a population of asymptomatic women. These findings allow us to identify an ideal anthropometric framework that can be used as a validated surgical endpoint for cosmetic and oncological procedures.

Examining the Antioxidant and Superoxide Radical Scavenging Activity of Anise, (Pimpinella anisum L. Seeds), Esculetin, and 4-Methyl-Esculetin Using X-ray Diffraction, Hydrodynamic Voltammetry and DFT Methods.

Pimpinella anisum L., or anise, is a plant that, besides its nutritional value, has been used in traditional medical practices and described in many cultures in the Mediterranean region. A possible reason for anise's therapeutic value is that it contains coumarins, which are known to have many biomedical and antioxidant properties. HPLC analysis in our laboratory of the anise extract shows the presence of the coumarin esculetin. We used a hydrodynamic voltammetry rotating ring-disk electrode (RRDE) method to measure the superoxide scavenging abilities of anise seeds and esculetin, which has marked scavenging activity. A related coumarin, 4-methyl-esculetin, also showed strong antioxidant activity as measured by RRDE. Moreover, this study includes the X-ray crystal structure of esculetin and 4-methyl-esculetin, which reveal the H-bond and the stacking intermolecular interactions of the two coumarins. Coordinates of esculetin crystal structure were used to perform a DFT study to arrive at the mechanism of superoxide scavenging. Besides performing a H(hydroxyl) abstraction in esculetin position 6 by superoxide, the scavenging also includes the presence of a second superoxide radical in a π-π approach. Both rings of esculetin were explored for this attack, but only the pyrone ring was effective. As a result, one product of esculetin scavenging is H2O2 formation, while the second superoxide remains π-π trapped within the pyrone ring to form an esculetin-η-O2 complex. Comparison with other coumarins shows that subtle structural differences in the coumarin framework can imply marked differences in scavenging. For instance, when the catechol moiety of esculetin (position 6,7) is shifted to position 7,8 in 4-methyl-7,8-dihydroxy coumarin, that coumarin shows a superoxide dismutase action, which, beside H2O2 formation, includes the formation and elimination of a molecule of O2. This is in contrast with the products formed through esculetin superoxide scavenging, where a second added superoxide remains trapped, and forms an esculetin-η-O2 complex.