Different effects of the companion antiretroviral drugs on dolutegravir trough concentrations.

BACKGROUND: Dolutegravir is widely used in different dual and triple antiretroviral regimens. Here, we sought to investigate the effect of the companion antiretroviral drug(s) on dolutegravir plasma trough concentrations in persons with HIV, with a focus on dual regimens. METHODS: Dolutegravir concentrations collected from October 2015 to March 2023 ( n  = 900) were stratified according to the main antiretroviral classes (NRTIs, NNRTIs, protease inhibitors) and according to single drugs. Dolutegravir concentrations measured in persons with HIV concomitantly treated with lamivudine were considered as the reference group. RESULTS: Dolutegravir trough concentrations were significantly higher in persons with HIV given protease inhibitors compared with the reference [1886 (1036-2940) versus 1575 (1026-2226) ng/ml; P  = 0.004]. The highest dolutegravir concentrations were measured in persons with HIV concomitantly treated with unboosted atazanavir [2908 (2130-4135) ng/ml]. Conversely, co-administration of darunavir/ritonavir resulted in significantly lower dolutegravir exposure [909 (496-1397) ng/ml; P  = 0.002 versus reference]. Among NNRTIs, the higher dolutegravir concentrations were measured in presence of rilpivirine [2252 (1489-2686); P  < 0.001 versus reference]. CONCLUSION: Dolutegravir trough concentrations are differently affected by individual antiretroviral drugs, with some drug combinations (i.e. dolutegravir/darunavir/cobicistat, or dolutegravir/rilpivirine) providing significantly higher than expected dolutegravir exposure. Such combinations might be advantageous when there are concerns about dolutegravir plasma exposure or resistance.

Vascular anatomy of the breast and its implications in the breast-sharing reconstruction technique.

The most frequently described breast-sharing procedure consists in a pedicled technique where the transferred lower breast pole is based on the lower perforators of the internal mammary (IM) artery. The current article investigates the vascular supply of the breast and its surgical implications in breast-sharing reconstruction. Contrast-enhanced magnetic resonance images of 55 patients (110 breasts) were retrospectively examined. A total of 473 branches of the IM, lateral thoracic (LT) and anterior intercostal (AI) arteries with a diameter greater than 0.5 mm were traced throughout their course in the breast. Distinct connections between the vessels were equally recorded. Although any vessel could vascularise any quadrant in the individual patient, blood supply to the lower quadrants came fundamentally from the AI arteries (76.2% of all the perforators). Lower IM branches (4th-5th) were seen to reach both lower quadrants in only 6.4% of the breasts, whereas LT branches did in 15.5%. In 86.4% of the breasts, at least a distinct AI perforator was seen to perfuse both lower quadrants. Well-defined connections between the IM and the LT arteries were observed in 41.8% of the breasts, always at or above the nipple-areola level. Other connections were far less common. Our study strongly indicates that the breast-sharing technique based on 4th-5th contralateral branches of the IM or LT arteries is unreliable in most patients. Given the unpredictable vascularization pattern in the lower breast pole, a preoperative imaging study is mandatory when the use of the contralateral breast is considered. Due to its accuracy, availability, and anatomical reliability, contrast-enhanced magnetic resonance is the best technique in the preoperative evaluation of the breast-sharing reconstruction.

Trigeminal trophic syndrome: An unusual nasal ulceration. A case report and review of the literature.

Trigeminal trophic syndrome is a rare condition characterized by self-inflicted persistent facial ulceration. It is believed to be consequent to central or peripheral insult to trigeminal nerve, which may have taken place even years before the ulcer development. The aggression to the nerve pathway causes dysesthesias in the trigeminal dermatomes that induce a self-mutilating behavior, with repetitive pinching or scratching in order to mitigate the altered sensation. Due to associated skin anesthesia, the patient does not interrupt manipulation of the affected area despite severe skin necrosis. Ulceration typically occurs in the ala nasi and may resemble other more common cutaneous diseases, such as tumors or infections. Given that this condition is not included in our daily clinical practice, the risk is that of a diagnostic delay with devastating functional and esthetic facial consequences. We present the case of a patient with a history of meningioma resection who developed this syndrome and we have reviewed the published literature to provide an update on the etiopathogenesis, diagnosis and treatment of this rare condition.

Reconstrucción del defecto de exenteración pélvico/perineal extendida con colgajo libre compuesto dorsal ancho-escapular-paraescapular y malla. La lógica en la elección / Reconstruction of extended pelvic/perineal exenteration defect with a composite latissimus dorsi-scapular-parascapular free flap and a mesh. The rationale behind the technique

Presentamos los fundamentos funcionales y reconstructivos en un caso de exenteración pélvica extendida. El propósito es analizar el defecto quirúrgico y los requerimientos reconstructivos, aspectos no suficientemente descritos en la literatura. Se trata de un varón de 62 años, con carcinoma epidermoide perineal de origen uretral (82x117x108 mm) que invadía vejiga, pelvis y fosa pararrectal. El defecto escisional fue reconstruido con un colgajo compuesto dorsal ancho-escapular-paraescapular y una malla bicapa (polipropileno y politetrafluoroetileno extendido). Describimos una reconstrucción multiplanar orientada a 3 requerimientos funcionales definidos: 1.- soporte visceral para evitar la herniación perineal; 2.- colapso del espacio muerto para minimizar el riesgo de infección; y 3.- cobertura cutánea estable en una región exigente. Sin complicaciones postoperatorias en el corto o largo plazo, el paciente puede deambular adecuadamente y se encuentra libre de enfermedad 1 año después de la intervención. Hasta donde hemos podido conocer, este caso presenta por primera vez el uso del colgajo compuesto descrito en la reconstrucción del defecto de exenteración pélvica

The article reports the functional, reconstructive rationale behind a case of extended pelvic exenteration. Our aim is to analyze the surgical defect and consequent reconstructive requirements, aspects which have not been adequately addressed in the literature. A case is presented of a 62-year-old man presenting with an 82x117x108 mm perineal squamous cell carcinoma of urethral origin invading bladder, pelvic bone and pararectal fossa. The resection defect was reconstructed with a composite latissimus dorsi-scapular-parascapular flap and a bilayer mesh (polypropylene and extended polytetrafluoroethylene). A multiplanar reconstruction is shown that addresses 3 distinct functional requirements: 1.- visceral support to prevent perineal herniation; 2.- collapse of dead space to minimize the risk of infection; and 3.- a stable skin cover for a demanding area. With no postoperative short or long-term complications, the patient is ambulating and free of disease at one-year follow-up. To the best of the authors' knowledge, this is the first report of the described composite flap in the reconstruction of the pelvic exenteration defect

Wearable Sensor-Based Biofeedback Training for Balance and Gait in Parkinson Disease: A Pilot Randomized Controlled Trial.

OBJECTIVES: To analyze the feasibility and efficacy of a novel system (Gamepad [GAMing Experience in PArkinson's Disease]) for biofeedback rehabilitation of balance and gait in Parkinson disease (PD). DESIGN: Randomized controlled trial. SETTING: Clinical rehabilitation gym. PARTICIPANTS: Subjects with PD (N=42) were randomized into experimental and physiotherapy without biofeedback groups. INTERVENTIONS: Both groups underwent 20 sessions of training for balance and gait. The experimental group performed tailored functional tasks using Gamepad. The system, based on wearable inertial sensors, provided users with real-time visual and acoustic feedback about their movement during the exercises. The physiotherapy group underwent individually structured physiotherapy without feedback. MAIN OUTCOME MEASURES: Assessments were performed by a blinded examiner preintervention, postintervention, and at 1-month follow-up. Primary outcomes were the Berg Balance Scale (BBS) and 10-m walk test (10MWT). Secondary outcomes included instrumental stabilometric indexes and the Tele-healthcare Satisfaction Questionnaire. RESULTS: Gamepad was well accepted by participants. Statistically significant between-group differences in BBS scores suggested better balance performances of the experimental group compared with the physiotherapy without biofeedback group both posttraining (experimental group-physiotherapy without biofeedback group: mean, 2.3±3.4 points; P=.047) and at follow-up (experimental group-physiotherapy without biofeedback group: mean, 2.7±3.3 points; P=.018). Posttraining stabilometric indexes showed that mediolateral body sway during upright stance was significantly reduced in the experimental group compared with the physiotherapy without biofeedback group (experimental group-physiotherapy without biofeedback group: -1.6±1.5mm; P=.003). No significant between-group differences were found in the other outcomes. CONCLUSIONS: Gamepad-based training was feasible and superior to physiotherapy without feedback in improving BBS performance and retaining it for 1 month. After training, 10MWT data were comparable between groups. Further development of the system is warranted to allow the autonomous use of Gamepad outside clinical settings, to enhance gait improvements, and to increase transfer of training effects to real-life contexts.