Search

Francesca Alberton,1 Laura Galli,2 Riccardo Lolatto,2 Caterina Candela,1 Nicola Gianotti,2 Matteo Chiurlo,2 Martina Ranzenigo,2 Martina Strano,2 Alessia Uglietti,3 Antonella Castagna1,2 1Infectious Diseases Unit, Vita Salute San Raffaele University, Milan, Italy; 2Infectious Diseases Unit, San Raffaele Scientific Institute, Milan, Italy; 3Medical Affairs Department, Infectious Diseases and Vaccines & Rare Diseases, Johnson&Johnson, Milan, ItalyCorrespondence: Alessia Uglietti, Medical Affairs Department, Infectious Disease and Vaccines & Rare Diseases, Johnson&Johnson, viale Fulvio Testi 280/6, Milan, 20126, Italy, Tel +39-344 2665502, Email augliett@its.jnj.comObjective: To evaluate the virological outcome of darunavir–cobicistat (DRVc)‐based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination.Methods: This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc‐based regimen with HIV‐RNA > 50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV‐RNA < 50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA < 50 copies/mL, last available visit, or loss to follow‐up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS.Results: A total of 176 individuals were included, and 120 (68.2%) achieved < 50 HIV‐RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004– 1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant–bearing protease inhibitor–resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up.Conclusion: Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.Keywords: HIV infection, antiretroviral therapy, ART, darunavir–cobicistat, DRVc, virological failure, VF

Objective: To evaluate tooth displacement and periodontal stress generated by the dual action vertical intra-arch technique (DAVIT) for open-bite correction using three-dimensional finite element analysis., Methods: A three-dimensional model of the maxilla was created by modeling the cortical bone, cancellous bone, periodontal ligament, and teeth from the second molar to the central incisor of a hemiarch. All orthodontic devices were designed using specific software to reproduce their morpho-dimensional characteristics, and their physical properties were determined using Young's modulus and Poisson's coefficient of each material. A linear static simulation was performed to analyze the tooth displacements (mm) and maximum stresses (Mpa) induced in the periodontal ligament by the posterior intrusion and anterior extrusion forces generated by the DAVIT., Results: The first and second molars showed the greatest intrusion, whereas the canines and lateral incisors showed the greatest extrusion displacement. A neutral zone of displacement corresponding to the fulcrum of occlusal plane rotation was observed in the premolar region. Buccal tipping of the molars and lingual tipping of the anterior teeth occurred with intrusion and extrusion, respectively. Posterior intrusion generated compressive stress at the apex of the buccal roots and furcation of the molars, while anterior extrusion generated tensile stress at the apex and apical third of the palatal root surface of the incisors and canines., Conclusions: DAVIT mechanics produced a set of beneficial effects for open-bite correction, including molar intrusion, extrusion and palatal tipping of the anterior teeth, and occlusal plane rotation with posterior teeth uprighting.

Objectives: Aims of this study were to assess the characteristics of Mpox among people with HIV (PWH) and describe the change of some immune-virological parameters during Mpox virus infection., Design: Case series of PWH diagnosed with Mpox between May and July 2022 at the Infectious Diseases Unit of San Raffaele Scientific Institute, Milan, Italy., Methods: Real-time PCR was used to detect Mpox virus on oropharyngeal, cutaneous, genital and rectal swabs, plasma, seminal fluids, and urines. The values of the CD4 + lymphocytes and HIV-RNA were assessed both at Mpox diagnosis and after Mpox virological clearance and were compared to those prior to Mpox. The relationship between the symptoms clinical duration of Mpox and the CD4 + cell count at diagnosis was assessed with Spearman's correlation coefficient., Results: Overall, 28 PWH on antiretroviral therapy with Mpox were evaluated. HIV-RNA did not substantially change at Mpox infection with respect to previous virological profile ( P  = 0.721). However, at time of Mpox diagnosis, we observed a detectable HIV-RNA (196 copies/ml) in one individual previously undetectable (HIV-RNA < 20 copies/ml) and an increase to 1.220 copies/ml in a previously viremic subject (HIV-RNA = 263 copies/ml). No significant differences in CD4 + cell count were found before and at time of Mpox diagnosis ( P  = 0.151) and a higher CD4 + cell count at Mpox diagnosis was marginally related to a lower duration of Mpox symptoms ( r  = -0.341, P  = 0.068)., Conclusions: Among PWH, we advise monitoring HIV viral load at Mpox diagnosis and during follow-up, as well as providing counseling on the results, due to the important individual and community implications., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Pre-exposure prophylaxis (PrEP) is effective for HIV prevention and is mostly used by men who have sex with men (MSM). The aim of this study was to describe the characteristics of a cohort of PrEP users at first PrEP counselling visits (baseline, BL)., Design: Cross-sectional study of a cohort of MSM receiving PrEP (Centro San Luigi, CSL-PrEP Cohort)., Setting: Secondary-level sexually transmitted infections (STI) centre in Milan, Italy, from May 2017 to May 2022., Participants: Overall, 624 MSM PrEP users were included; most users were Caucasian (97%), attended university (64%), with a median BL age of 34.5 years., Results: Overall, 45% choose the daily-based PrEP regimen, 55% the event-based one. An increasing trend in PrEP counselling visits was observed (p=0.024). The majority had between 10 and 19 partners in the 3 months before BL and 41% were chemsex users. All had a HIV Incidence Risk Index for MSM (HIRI-MSM)>10, 54% between 20 and 29. Overall, 50% had ≥1 previous STI and 22% ≥1 BL STI. BL chlamydia (10%) was often more frequent than in the past (7%). The number of sexual partners was associated with BL chlamydia (p<0.001), gonorrhoea (p=0.002) and syphilis (p=<0.001), HIRI-MSM with chlamydia (p=0.001) and gonorrhoea (p=0.008), chemsex use with chlamydia (p=0.003) and gonorrhoea (p=0.030)., Conclusions: We observed an unbalanced access to PrEP in respect to all key populations which might benefit from PrEP, with a similar choice for event-based or daily-based regimens. High-risk behaviours and STIs were frequently observed. History of chlamydia was very frequently high in asymptomatic MSM at BL, compared with what observed before access to PrEP. High-risk behaviours and HIRI-MSM were associated with most of STIs., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Vaccines have historically played a pivotal role in reducing the burden of infectious diseases andnow play a crucial role in the setting of sexually transmitted infections (STIs). However, there remainseveral unmet goals: vaccines are available only for viral STIs, vaccination accessibility anduptake remain disproportionate worldwide, and no effective vaccine has been developed for HCV.Moreover, there are no vaccines against bacterial STIs: fewer investments in research have beenmade, because vaccines are not a top priority due to the availability of effective treatments. However,higher rates of resistance to all available antibiotics has led to a shift in research priorities. Severalpromising vaccine candidates have been identified or are being investigated in pre-clinical or clinicaltrials, although further understanding of the immunogenicity, effectiveness and delivery strategiesof already licensed vaccines is needed. This paper focuses on current research efforts to developvaccines against bacterial (e.g. gonorrhoea, chlamydia and syphilis) and viral (e.g. HCV) STIs. Wealso review current indications and evidence of effectiveness of already available vaccines (e.g. HAV,HBV and HPV) and discuss open issues.

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions, resulting in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. The management of a newborn with suspected 46,XY DSD remains challenging. Newborns with 46,XY DSD may present with several phenotypes ranging from babies with atypical genitalia or girls with inguinal herniae to boys with micropenis and cryptorchidism. A mismatch between prenatal karyotype and female phenotype is an increasing reason for presentation. Gender assignment should be avoided prior to expert evaluation and possibly until molecular diagnosis. The classic diagnostic approach is time and cost-consuming. Today, a different approach may be considered. The first line of investigations must exclude rare life-threatening diseases related to salt wasting crises. Then, the new genetic tests should be performed, yielding increased diagnostic performance. Focused imaging or endocrine studies should be performed on the basis of genetic results in order to reduce repeated and invasive investigations for a small baby. The challenge for health professionals will lie in integrating specific genetic information with better defined clinical and endocrine phenotypes and in terms of long-term evolution. Such advances will permit optimization of counseling of parents and sex assignment. In this regard, society has significantly changed its attitude to the acceptance and expansion beyond strict binary male and female sexes, at least in some countries or cultures. These management advances should result in better personalized care and better long-term quality of life of babies born with 46,XY DSD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bertelloni, Tyutyusheva, Valiani, D'Alberton, Baldinotti, Caligo, Baroncelli and Peroni.)

In the last decades many innovations have improved the hip replacement and the hip reconstruction surgery such as the introduction of the robotic-arm assisted surgery associated with the direct anterior approach (DAA). This surgical approach for total hip arthroplasty (THA) is growing in popularity and its effectiveness has been demonstrated to improve patients' outcomes, especially regarding more accurate implant placement, less post operative pain, faster recovery and lower of prosthesis dislocation risk. The robotic-arm assisted surgery is another really great innovation for the orthopedic surgeons. It allows to create a patient-specific THA pre-operative planning and to perform a much more accurate surgical procedure. This article outlines authors' surgical technique of performing accurate pre-operative planning and robotic-assisted THA using direct anterior approach based on the experience of 534 patients and to discuss details of this technique.

WS diagnosis is often delayed since misdiagnosed as autoimmune diabetes. The rarity of the condition and the absence of other diseases at diabetes diagnosis might make extremely challenging the recognition of WS. However the novel compound heterozygosity for the here reported mutations, seems to confer a mild phenotype among the spectrum of WS manifestations., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Progressive care improvement for differences of sex development (DSD), regarding diagnosis communication, psychological, medical and surgical management has been claimed., Aim of the Study: To assess clinical management, quality of life (QoL) and the general psychosocial adjustment of individuals with 46,XY DSD. Some differences related to age at diagnosis are investigated., Design: Cross-sectional study using standardized questionnaires., Population: Forty-three Caucasian females with 46,XY DSD (self declared diagnoses: complete androgen insensitivity syndrome, n = 34; complete gonadal dysgenesis, n = 1; 5α-reductase deficiency, n = 4; Leydig cell hypoplasia, n = 1; unknown diagnosis, n = 3; age years: 31.5 ± 9.6 [range 18-57 years])., Setting: University Hospitals., Methods: Subjects were required to fill in questionnaires (ABCL, WHOQOL, dedicated 17-item questionnaire). Academic and socioeconomic data were compared with those of the Italian population. QoL and psychological data were compared with those of a comparison group (46,XX healthy females: n = 43; age, years: 34.5 ± 9.7, range 22-51 years)., Results: Present sample of women living with 46,XY DSD were well adapted and were higher achievers than controls, both in educational and professional life. They showed good QoL, but they appeared less satisfied in psychological and social areas. They had borderline mean scores and statistically higher scores than the comparison group for depression, anxiety, internalizing and externalizing problems. Younger persons living with a 46,XY DSD showed better psychosocial adjustment than older ones. Younger women showed lower age at diagnosis communication. Psychological support was more often proposed at the time of diagnosis communication to younger individuals, and they undertook it more frequently than older ones., Conclusions: Italian people living with 46,XY DSD were well adapted and successful; they reported a good QoL but showed higher degree of psychological distress than the comparison group. Lower psychological distress in younger women could indicate some positive effects of changes in management., (© 2015 International Society for Sexual Medicine.)

Objective: To compare the psychological adjustment and behaviour of congenital hypothyroidism (CH) children and their parents with a control group., Study Design: A cross-sectional study was carried out with 84 CH subjects diagnosed by neonatal screening (range 2.7-18.6 years), subdivided into four age groups: group 1 (2-5 years); group 2 (6-10 years); group 3 (11-13 years); and group 4 (14-18 years) and was compared with an age-matched control group. Patients were assessed using two questionnaires: Child Behaviour Checklist for parents and Youth Self-Report for children over 11 years of age., Results: In groups 1, 3 and 4, total score (TS), internalising score (IS=problems within the self) and externalising score (ES=conflicts with other people) as reported by parents were not significantly different in CH patients and in controls. In group 2, parents of CH children showed values of TS (P<0.05), IS (P<0.05), ES (P<0.05) and scores on other scales significantly higher than controls. In self-reports of groups 3 and 4, the behavioural scales were not significantly different in CH patients and in controls., Conclusions: Paediatricians should be informed about the increased risk of the development of behavioural problems at primary school age in CH patients. At this age special attention should be paid to parental worries and anxiety. However, it can be reassuring for the patients and parents to know that the problems may be related to CH, and that they may spontaneously disappear.

Objective: To evaluate self and parent reports on quality of life (QoL) and psychological adjustment of youths with type 1 diabetes, in comparison to a general paediatric population, and identify relationships between disease duration, metabolic control and psychological parameters., Research Design and Methods: Participants included 70 youths with type 1 diabetes and their parents. They were compared with 70 non-diabetic subjects. Data were analyzed in the whole group and in subgroups aged 6-10, 11-13 and 14-18 yr. All cases performed pediatric QoL, Child Behaviour Checklist, filled in by parents, and Youth Self-Report, filled in by youths. Data were compared with haemoglobin A1c (HbA1c) values and disease duration., Results: Self-reports showed a psychological adjustment of youths with type 1 diabetes similar to that of controls. Parent reports showed that parents of children with type 1 diabetes were more worried than those of controls (p < 0.01). Adolescents showed a worse QoL and more frequent psychological disturbances. In this group, for youth and parent reports, HbA1c levels correlated positively with psychological problems (p < 0.05) and negatively with QoL (p < 0.05). Only for parent reports, in the whole group and in subgroups aged 6-10 and 11-13 yr, disease duration correlated positively with psychological adjustment (p < 0.05)., Conclusions: Before adolescence, youths with type 1 diabetes showed only slight problems in psychological adjustment and QoL, with an association with disease duration reported by parents. In adolescence, both youths and their parents reported more emotional and behavioural problems, independent of disease duration. Better metabolic control and psychological well-being seemed directly related.