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Background/Objectives : Out of 39.9 million adults living with HIV in 2022, 20 million were women. Despite bearing a significant burden, women remain underrepresented in clinical trials, including those for antiretroviral treatments (ART). This study evaluates the safety and efficacy of the bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) regimen in a real-life cohort of 99 women with HIV (females with HIV, FWH) over 48 and 96 weeks. Methods : A retrospective cohort study utilized data from the Sardinian HIV Network and Sicilian HIV Cohort (SHiNe-SHiC) research group. The study included FWH, who started B/F/TAF as a treatment switch. The primary objectives were achieving and maintaining an HIV RNA level of <50 copies/mL at 48 and 96 weeks. Secondary objectives included treatment safety, durability, and reasons for discontinuation. Data on demographics, viro-immunological markers, lipid profiles, and treatment interruptions were extracted for analysis. Results : Among the 99 FWH, the median age was 51.9 years, and the median duration of HIV was 15.1 years. At baseline, 80.8% had undetectable HIV-RNA, which increased to 93.8% at 96 weeks. There was a statistically significant increase in CD4 cells/mL (48w p < 0.001, 96w p < 0.001) and CD4/CD8 ratio (48w p < 0.009, 96w p < 0.048), and reductions in total cholesterol (48w p < 0.003, 96w p < 0.006) and LDL (48w p < 0.004, 96w p < 0.009) levels at 48 and 96 weeks. Nine treatment interruptions were noted, with one due to adverse events. The regimen was well-tolerated overall. Conclusions : B/F/TAF demonstrated high efficacy and safety in this real-world cohort of FWH, highlighting the critical need for gender-focused research in HIV treatment. Ensuring equitable access to effective treatment options for women is imperative for the global health community's efforts to eliminate HIV.

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity., (© 2024. The Author(s).)

Background: Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario., Methods: We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer-Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen., Results: 1145 patients [median (IQR) age 74 (62-83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0-23 points), medium (24-35), and high (≥ 36)., Conclusions: The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies., (© 2024. The Author(s).)

Clinical trials demonstrated the role of vaccines and antiviral treatments against SARS-CoV-2 in reducing the likelihood of disease progression and death. However, there are limited data available regarding the time to negativity of people who received these treatments. Further, several comorbidities and risk factors might affect the impact of vaccines and antiviral treatments. To this end, we aimed to evaluate and disentangle the impact of anti-SARS-CoV-2 treatments and that of underlying clinical factors associated with a shortened length of SARS-CoV-2 infection. Hence, we recorded the timeframe of positive nasopharyngeal swab in people infected while being hospitalized for reasons other than SARS-CoV-2 infection. All patients who died or were discharged with a positive swab were excluded from the study. A total of 175 patients were included in this study. Clinical conditions encompass malignancies, immunological disorders, cardiovascular, metabolic, neurodegenerative, and chronic kidney disease. Most of the participants (91.4%) were vaccinated before admission to the hospital, and 65.1% received antiviral treatment within three days after the symptom's onset. Unvaccinated patients had a longer median time to negativity than people who received at least two doses of vaccine (18 vs. 10 days). Concerning the clinical conditions of all patients, multivariate analysis highlighted a lower probability of 14-day conversion of antigenic test positivity in patients with hematological malignancy, including those vaccinated and those exposed to antiviral therapies. In conclusion, our data showed that prompt administration of antiviral treatments accelerates the clearance of SARS-CoV-2. Further, in the elderly patients under study, previous vaccination and antiviral treatment synergize to reduce time to negativity. This translates into a shorter hospitalization time and a lower risk of transmission through patients and connected healthcare workers in a hospital ward setting, with considerable improvement in cost-effective care management.

Background: Since the beginning of the SARS-CoV-2 pandemic, millions of people have been infected and died. Different therapeutic approaches have been recommended, but only a few have shown clinical advantages. Low-molecular-weight heparin (LMWH) has been recommended to prevent COVID-19-related thrombo-embolic events. We aimed to evaluate the impact of early treatment with LMWH on hospital admission and death in patients with SARS-CoV-2 infection., Methods: We conducted an observational monocentric retrospective study to evaluate the preventive role of LMWH on the mortality rate of COVID-19 patients. SARS-CoV-2 infected patients were recruited from the beginning of the Italian epidemic to March 31, 2021. We excluded patients with missing data and those chronically exposed to LMWH. Treatment prescription was based on international and national guidelines and modified depending on clinical presentation and drug-drug interactions., Results: Seven hundred thirty-four SARS-CoV-2 infected patients were recruited, with 357 (48.6%) males and a median (IQR) age of 77.9 (65-85.7) years. 77.5% of people developed SARS-CoV-2-related symptoms and 62.8% were admitted to the hospital, and 20.2% died. Four hundred ninety-two (67%) started LMWH. In particular, 296 (40.3%) were treated within five days since symptoms onset. At logistic regression, early LMWH therapy was associated with lower mortality. Furthermore, remdesivir treatment showed a lower risk of death. On the contrary, age, BMI>30 kg/m 2 , neurological diseases, fever or dyspnea were associated with an increased risk of death., Conclusions: Early treatment with LMWH was associated with lower mortality in our cohort. Further studies are needed to better assess the role of wider LMWH administration in terms of timing and regimen dose.

After 40 years of its appearance, human immunodeficiency virus (HIV) infection remains a leading public health challenge worldwide. Since the introduction of antiretroviral treatment (ART), HIV infection has become a chronic condition, and people living with HIV could have life expectancies close to those of the general population. People with HIV often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases. Nowadays, several vaccines are available against bacteria and viruses. However, national and international vaccination guidelines for people with HIV are heterogeneous, and not every vaccine is included. For these reasons, we aimed to perform a narrative review about the vaccinations available for adults living with HIV, reporting the most updated studies performed for each vaccine among this population. We performed a comprehensive literature search through electronic databases (Pubmed-MEDLINE and Embase) and search engines (Google Scholar). We included English peer-reviewed publications (articles and reviews) on HIV and vaccination. Despite widespread use and guideline recommendations, few vaccine trials have been conducted in people with HIV. In addition, not all vaccines are recommended for people with HIV, especially for those with low CD4 cells count. Clinicians should carefully collect the history of vaccinations and patients' acceptance and preferences and regularly check the presence of antibodies for vaccine-preventable pathogens.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoma belonging to the marginal zone lymphoproliferative disorders. Usually, SMZL occurs with indolent presentation and, when required, the standard of care is represented by rituximab-based regimens. No direct comparison of different rituximab-based combinations and polychemotherapy regimens has been conducted to date. In a monocentric cohort of 68 SMLZ patients, we showed that rituximab in monotherapy or in combination with bendamustine, compared with rituximab associated with the polychemotherapy cycle cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), resulted in a higher 5-year progression-free survival (91.3 ± 9% and 75 ± 15.7% vs. 30.8 ± 12.1%, p < 0.001). Platelets at diagnosis <100 ×109/L (p = 0.034, HR = 4.3) and transformation into diffuse large B-cell lymphoma (p = 0.031, HR = 4.3) were associated with a lower overall survival., (© 2020 S. Karger AG, Basel.)

To evaluate whether protein changes in extracellular matrix of dental biofilm are a unique property of sucrose, this in situ study was conducted using as active control glucose and fructose, the sucrose monosaccharide constituents. Proteins were analyzed by two-dimensional electrophoresis followed by LC-MS/MS after trypsin digestion. Absence or lower abundance of calcium-binding proteins and higher abundance of prolactin-induced proteins were found in biofilm formed in the presence of sucrose or its monosaccharide constituents compared with water, the negative control group. The data suggest that besides sucrose, other dietary carbohydrates may also provoke a change in the protein profile of extracellular matrix of dental biofilm formed., (Copyright © 2012 S. Karger AG, Basel.)

The objective of this study was to evaluate the efficacy of olanzapine (OLA) in heroin-dependent patients affected by comorbid schizophrenia spectrum disorders (SSD). Sixty-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for heroin dependence and the criteria for SSD (schizophrenia and schizotypal and schizoaffective-bipolar disorders) were treated in a 12-week prospective observational trial of substitution treatment in combination with OLA or typical antipsychotic haloperidol. Patients were included into 2 subgroups, in relationship with treatment, for the evaluation of the end points at week 12: group 1, SSD treated with OLA (35 patients); group 2, SSD treated with haloperidol (26 patients). Efficacy measures were retention in treatment, Symptoms Checklist-90 score changes, negative urinalyses results, and craving reduction. The rate of patients who remained in treatment at week 12 in group 1 SSD, treated with OLA, was significantly higher (32[91.4%]) than that of group 2 SSD (13 [50%]), treated with the typical antipsychotic (P < 0.001). The decrease in Symptoms Checklist-90 total scores from baseline, as expression of an improvement in comorbid psychopathology in the patients who completed the treatment, was significantly more consistent in group 1 than in group 2 patients (P < 0.01). Among the patients who remained in treatment, 64.4% achieved early full substance abuse remission, whereas 35.6% achieved partial substance abuse remission, with a significant difference between 1 (78.13%) and 2 (46.1%) treatment subgroups (P = 0.04). Although obtained by an observational-open clinical study with multiple limitations, our findings suggest that OLA may be able to increase retention and negative urinalyses rates during opioid agonist maintenance treatment in the patients with SSD and to improve psychopathology symptoms and tolerability in these dually diagnosed heroin addicts. Preliminary accurate diagnostic assessment and appropriate psychoactive medication in addicted patients affected by schizophrenia and schizotypal and schizoaffective-bipolar disorders seem to obtain less adverse effects and a more successful outcome of drug dependence treatment.

Objective measures of experimentally induced aggressiveness were evaluated in heroin-dependent patients (HDP), 15 receiving buprenorphine (BUP) and 15 receiving methadone (METH) treatment. HDP were randomly assigned to BUP and METH groups. Fifteen healthy subjects (CONT) were included in the study as controls. During a laboratory task, the Point Subtraction Aggression Paradigm, subjects earned monetary reinforcement and could respond by ostensibly subtracting money from a fictitious subject (the aggressive response). Money-earning (points maintained) responses did not differ in BUP patients and in controls. In contrast, point-maintained responses were significantly lower in the group of HDP treated with METH than in both the BUP and CONT groups. Aggressive responses were significantly higher in the HDP group than in the CONT group. No significant differences in aggressive responses were found between the BUP and METH groups. Baseline concentrations of plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) were higher in HDP than in CONT. During the experimental task, ACTH and CORT increased significantly less in METH patients than in BUP patients and CONT. Norepinephrine (NE) and epinephrine (EPI) levels increased significantly more in HDP than in CONT, without any difference between the METH and BUP patients. PSAP aggressive responses positively correlated with NE and EPI changes, as well as with Buss-Durkee Hostility Inventory (BDHI) scores in both METH and BUP patients and also in CONT subjects. No correlation was found between the extent of heroin exposure, drug doses and aggressiveness levels. BUP, similarly to METH, does not seem to affect outward-directed aggressiveness, as aggressive responses related more to monoamine levels and personality traits than to the action of opioid agonists. Money-earning responses seemed to be unimpaired in BUP patients.

Polymorphism of a variable number of tandem repeats (VNTR) in the 3' untranslated region of exon 15 of the SLC6A3 gene, coding for the dopamine transporter (DAT), was analysed to test whether length variation contributes to differences in the individual susceptibility to aggressive - criminal behaviour and liability to heroin dependence. The repeat number of the DAT polymorphism was assessed in 125 healthy subjects and 104 heroin-dependent subjects (including 52 addicted individuals with violent behaviour and criminal records). There was no significant difference in the frequencies of genotypes and alleles between heroin-dependent subjects and control subjects. On the contrary, there was a significant difference between offenders and non-offenders, p = 0.004 and p = 0.002, respectively, among heroin-dependent subjects. No association was found between DAT polymorphism and history of suicide. Buss - Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p < 0.001) and in antisocial - violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p < 0.005). The regression analysis of BDHI subscales, performed to provide an estimate of the magnitude of any potential effect on the risk of aggressiveness associated with the variants in DAT VNTR, showed that the presence of the 9 - 9 genotype significantly increases the risk of irritability and direct aggressiveness more than six and 10 times with respect to the 9 - 10 genotype. Our findings suggest that the 9-repeat allele of the DAT polymorphism confers increased susceptibility to antisocial - violent behaviour and aggressiveness, rather than drug dependence per se in heroin-dependent males.

Objective measures of experimentally induced aggressiveness were evaluated in 20 abstinent heroin-dependent subjects, in comparison with 20 normal healthy male subjects. All the subjects were preliminarily submitted to DSM-IV interviews, Buss-Durkee Hostility Inventory (BDHI) and Minnesota Multiphasic Personality Inventory (MMPI II). During a laboratory task, the Point Subtraction Aggression Paradigm (PSAP), subjects earned monetary reinforcers with repeated button presses and were provoked by the subtraction of money, which was attributed to a fictitious other participant. Subjects could respond by ostensibly subtracting money from the fictitious subject (the aggressive response). Money-earning responses were not different in drug-free heroin addicts and controls during the first two sessions and significantly lower during the third session in heroin-dependent subjects (t=2.99, P<.01). Aggressive responses were significantly higher (F=4.9, P<.01) in heroin addicted individuals, in comparison with controls. During the experimentally induced aggressiveness, plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) concentrations increased less significantly, and norepinephrine (NE) and epinephrine (EPI) levels, together with heart rate (HR), increased more significantly in abstinent heroin-dependent subjects than in healthy subjects. PSAP aggressive responses positively correlated with catecholamine changes, BDHI "direct" and "irritability" scores, MMPI "psychopathic deviate" scores in heroin-dependent subjects and controls, and with CORT responses only in healthy subjects. No correlation was found between heroin-exposure extent (substance abuse history duration) and aggressiveness levels. The present findings suggest that heroin-dependent patients have higher outward-directed aggressiveness than healthy subjects, in relation with monoamine hyperreactivity, after long-term opiate discontinuation. Aggressiveness in heroin addicts seems to be related more to the personality traits than to drug effects. The impairment of hypothalamus-pituitary-adrenal (HPA) axis in abstinent addicted individuals could be due to a long-lasting action exerted by opiates on proopiomelanocortin (POMC) or to a premorbid psychobiological condition, in association with increased sympathetic arousal.

Fifteen 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') users who did not have other drug dependencies or prolonged alcohol abuse and 15 control subjects were studied. All the subjects were exposed to the same psychosocial stressor (Stroop Color-Word Interference Task, public speaking and mental arithmetic in front of an audience) 3 weeks after MDMA discontinuation. Plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol were measured immediately before the tests began and at their end, 30 min later. Growth hormone (GH) responses to the dopaminergic agonist bromocriptine and psychometric measures (Tridimensional Personality Questionnaire, Minnesota Multiphasic Personality Inventory, Buss-Durkee Hostility Inventory) were also obtained 4 weeks after MDMA discontinuation for the same subjects. ACTH and cortisol basal levels were significantly higher in ecstasy users than in control subjects. In contrast, ACTH and cortisol responses to stress were significantly blunted in MDMA users. The sensitivity of dopamine D2 receptors, reflected by GH responses to bromocriptine challenge, was reduced in MDMA users compared with controls. The responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis (ACTH and cortisol delta peaks) correlated directly with GH areas under curves in response to bromocriptine, and inversely with psychometric measures of aggressiveness and novelty seeking. No correlation was found between hormonal measures and the extent of MDMA exposure. Reduced D2 receptor sensitivity, HPA basal hyperactivation and reduced responsiveness to stress may represent a complex neuroendocrine dysfunction associated with MDMA use. The present findings do not exclude the possibility that dopamine dysfunction partly predated MDMA exposure.

The present study investigated clinical, cardiovascular and neuroendocrine consequences of rapid opioid detoxification (ROD) in heroin-dependent individuals, affected, or not, by comorbid antisocial personality disorder (ASPD). Thirty-two patients underwent ROD and subsequent treatment with daily naltrexone: 3 days detoxification procedures were performed utilizing clonidine, baclofen, oxazepam and ketoprofene, without anaesthesia. Withdrawal symptoms, mood changes, cardiovascular indexes (heart rate, blood pressure), norepinephrine (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH) and cortisol (CORT) were evaluated during naloxone-naltrexone administration on the second day of detoxification treatment. The patients were divided into two groups following DSM-IV criteria for ASPD. Group A comprised 14 ASPD patients and group B comprised 18 patients without ASPD. Slight and transient withdrawal symptoms and mood changes were demonstrated on the second day in the whole sample of patients, in association with a significant, but moderate, elevation of heart rate, blood pressure, NE (two-fold), EPI (five-fold), ACTH (two-fold) and CORT (two-fold) plasma levels, in response to opioid receptor-antagonist administration. When evaluated separately in ASPD (group A) and non-ASPD patients (group B), significantly higher withdrawal symptoms and mood changes, heart rate, blood pressure, NE, ACTH and cortisol levels were observed in ASPD subjects. By contrast, no differences were found in EPI responses to naloxone-naltrexone administration between group A and B patients. The significant differences demonstrated in clinical and neuroendocrine responses to opioid receptor-antagonist administration, in relation to personality traits, could be due to reduced alpha-adrenergic receptor sensitivity, which was previously reported in ASPD, with a possible impairment of clonidine action. Our study suggests that a detailed diagnostic assessment before detoxification procedure may help to predict treatment outcome.

Twelve (+/-) 3,4-methylenedioxymethamphetamine (MDMA) users, who did not show other drug dependencies or prolonged alcohol abuse (group A), and 12 control subjects (group B) were included in the study. Prolactin (PRL) and growth hormone (GH) responses to the dopaminergic agonist bromocriptine (BROM) and psychometric measures were evaluated 3 weeks after MDMA discontinuation. PRL decreased both in A and B subjects after BROM suppression, without any significant difference between the two groups. PRL responses to BROM in MDMA users were in the normal range. In contrast, GH responses to BROM stimulation were found significantly reduced in ecstasy users, in comparison with control subjects (P < 0.001; F = 6.26). MDMA users showed higher scores on the Novelty Seeking (NS) scale at the Three dimensional Personality Questionnaire (TPQ), on direct aggressiveness subscale at Buss Durkee Hostility Inventory (BDHI), on subscale D (depression) at Minnesota Multiphasic Personality Inventory (MMPI 2) and on Hamilton Depression Rating Scale (HDRS) than control subjects. PRL areas under the curves (AUCs) showed a significant inverse correlation with NS scores both in A and B subjects. GH AUCs directly correlated with NS scores in healthy subjects, but not in MDMA users. No other psychometric measure correlated with hormonal responses. GH AUCs were inversely correlated with the measures of MDMA exposure (r = -0.48; P < 0.01). Lower GH response to BROM in A subjects (MDMA users) could reflect reduced D2 receptor sensitivity in the hypothalamus, possibly due to increased intrasynaptic dopamine concentration. Although the hypothesis of dopaminergic changes associated with a premorbid condition cannot be completely excluded, the inverse correlation between DA receptors sensitivity and the extent of ecstasy exposure may suggest a direct pharmacological action of MDMA on brain dopamine function in humans., (Copyright 2002 Elsevier Science B.V.)

Long lasting 5HT system impairment has been demonstrated in experimental animals exposed to ecstasy use; MDMA seems to be able to induce behavioral conditioning and reiterated use because of its dopaminergic action. Among behavioral aspects of ecstasy users mood disorders, irritability and difficult in relationships, interpersonal difficulties, high levels of impulsiveness and hostility, high sensation seeking, cognitive and attentive deficit have been reported. A derangement of serotonin system function was reported also in humans exposed to ecstasy, as confirmed by neuroendocrine challenges and brain imaging techniques. Recent researches suggest functional changes in dopaminergic system too. The persistence of behavioral and neuroendocrine changes many months after MDMA's discontinuation, indicate a lack of reversibility in the dysfunction induced by ecstasy, or the persistence of psychobiological traits that could preexist to MDMA exposure, possibly involved in substance abuse vulnerability.