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Background: Cytomegalovirus (CMV) infection is the most common and serious congenital infection, with universal screening in pregnancy, standardized therapy, and a vaccine still lacking. Study design: In the 1990s, we noted that intravenous ganciclovir did not cure some children with severe sequelae due to congenital cytomegalovirus (CMV) infection. Therefore, we performed an open randomized trial using intravenous foscarnet as an alternative to intravenous ganciclovir in 24 infants (12 in each therapy group), all with severe neurological manifestations due to congenital CMV infection. Nine and five infants, belonging to the foscarnet or ganciclovir group, respectively, had abnormal hearing. One infant in each group also had chorioretinitis. Concomitantly, 12 CMV-infected infants with similar manifestations, who did not receive any therapy, were used as controls. The results of short-term (2 years) and long-term (7–29 years, mean 22.2) follow-up are reported herein. Short-term results: Neurological outcomes were normal in five of the twelve children who were treated with foscarnet, compared to nine of the twelve children given ganciclovir. None of the untreated children were healthy. There was a statistically significant difference (p = 0.023) between the treated and untreated children. Hearing was normal in four of the twelve children treated with foscarnet, seven of the twelve children treated with ganciclovir, and two untreated children. Long-term-results: Two children in both therapy groups died before the age of 17 years, and six untreated children died between 7 and 26 years of age. Neurological outcomes were normal in three of the ten children treated with foscarnet, in two of the ten treated with ganciclovir, and in none of the untreated children. Hearing was normal in two children treated with foscarnet, in six children treated with ganciclovir, and in one untreated child. Conclusions: Intravenous ganciclovir and foscarnet were found to be safe at long-term follow-up and appeared to be capable of mitigating the neurological and auditory consequences of congenital CMV disease at the short-term follow-up. However, there was progressive worsening of the symptomatology in all three groups, with a statistically significant increase in the number of deaths (p = 0.035) among 4 of the 24 children in the therapy groups and 6 of the 12 untreated children.

Capnocytophaga canis is an uncommon cause of septic shock. Only three cases have been previously reported in the literature. In this article, we describe the case of a 70-year-old male admitted to the intensive care unit for septic shock of unknown origin. On day 2, one anaerobic bottle out of the two sets taken at admission turned positive with Gram-negative bacilli. The pathogen was identified by 16S rRNA gene as C. canis. The strain was characterized and compared with other clinical isolates of Capnocytophaga spp.

Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant's median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.

Background: Dolutegravir-containing maintenance therapy is a promising simplification strategy for virologically suppressed HIV-infected individuals. However, most of the available data to inform this strategy come from small, uncontrolled studies. We estimated the proportion of HIV-infected patients experiencing virological failure (VF) and developing drug resistance on dolutegravir (DTG)-based maintenance therapy. Methods: We searched Medline, Embase, Cochrane Central, Web of Science, and conference abstracts for studies assessing VF on DTG-based maintenance therapy. Studies including ≥5 adults with an undetectable viral load on antiretroviral therapy (ART) who switched to a DTG-based mono- or dual therapy were included. Pooled proportions of VF were estimated using random-intercept logistic meta-regression and acquired drug resistance mutations described for each strategy. Results: Of 1719 studies considered, 21 met our selection criteria, including seven interventional and 14 observational studies. Eight studies including 251 patients assessed VF on DTG monotherapy and fourteen studies including 1670 participants VF on dual therapy. The participant's median age ranged from 43 to 63 years, their median nadir CD4 count from 90 to 399 cells/µl, and 27.6% were female. The proportion of participants experiencing VF on DTG-monotherapy was 3.6% (95% confidence interval [CI] 1.9-6.7) at 24 weeks and 8.9% (95% CI 4.7-16.2) at 48 weeks. Resistance mutations developed in seven (3.6%) participants on DTG-monotherapy. Among patients on dual therapy, ten (0.7%, 95% CI 0.4-1.3) experienced VF by 48 weeks and none developed resistance to DTG. In adjusted analyses, VF at 24 weeks was less likely on dual therapy than on monotherapy (adjusted odds ratio: 0.10, 95% CI 0.03-0.30). Conclusions: Whereas VF is relatively common on DTG maintenance monotherapy, DTG-based dual therapy appears to be a promising simplification strategy for individuals with a suppressed HIV viral load on triple-ART.

Dolutegravir (DTG)-based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL'HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART. SIMPL'HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel-Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than -12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference -1.2%; 95% CI -7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI -5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference -1.1%; 95% CI -9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study's main limitations included a rather small proportion of women included, the open label design, and its short duration. In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals. ClinicalTrials.gov NCT03160105.

Several narrow or broadband spectral indices can be calculated at varying spatial and spectral resolution, which can then be correlated with the physiological and nutritional status of the leaves. In a three-year trial carried out on fruiting, potted cv. Barbera grapevines subjected to full (N+) or no (N0) nitrogen supply, seasonal evolution of different leaf spectral indices were correlated with non-destructive chlorophyll readings (Minolta SPAD meter), leaf gas exchange, and vine performance. Throughout the entire trial, N starvation resulted in greater-than-proportional limitation of vine yield as compared to vegetative growth (55% compared to 26% less than values measured on N+). Indices calculated within the red-edge spectral domain had highest sensitivity to relative change between N+ and N0, also indicating that the promptest response was recorded at the median shoot zone level. Twelve broadband indices were linearly correlated with leaf blade N concentration at veraison, indicating that N values ≤ 1.8% of dry matter identify a limiting N status. Any of these indices collected at the leaf level can be reliably used as a non-destructive predictor of N availability, albeit due to significant between-year variation in their absolute values at a given N level, readings should always include a well-supplied N treatment.

Stereotactic radiosurgery (SRS) for multiple brain metastases can be delivered with a single isocenter and non-coplanar arcs, achieving highly conformal dose distributions at the cost of extreme modulation of treatment machine parameters. As a result, SRS plans are at a higher risk of patient-specific quality assurance (PSQA) failure compared to standard treatments. This study aimed to develop a machine-learning (ML) model to predict the PSQA outcome (gamma passing rate, GPR) of SRS plans. Five hundred and ninety-two consecutive patients treated between 2020 and 2024 were selected. GPR analyses were performed using a 3%/1 mm criterion and a 95% action limit for each arc. Fifteen plan complexity metrics were used as input features to predict the GPR of an arc. A stratified and a time-series approach were employed to split the data into training (1555 arcs), validation (389 arcs), and test (486 arcs) sets. The ML model achieved a mean absolute error of 2.6% on the test set, with a 0.83% median residual value (measured/predicted). Lower values of the measured GPR tended to be overestimated. Sensitivity and specificity were 93% and 56%, respectively. ML models for virtual QA of SRS can be integrated into clinical practice, facilitating more efficient PSQA approaches.

The aim of the “Smuovi La Salute” (“Shake Your Health”) project was to implement an integrated and comprehensive model to prevent and treat overweight and obesity in low socioeconomic status (SES) and minority groups living in three different districts in the north of Italy. An app and a cookbook promoting transcultural nutrition and a healthy lifestyle were developed, and no-cost physical activities were organized. Healthy lifestyle teaching was implemented in 30 primary school classrooms. Learning was assessed through pre- and post-intervention questionnaires. At the Obesity Pediatric Clinic, overweight and obese children of migrant background or low SES were trained on transcultural nutrition and invited to participate in the project. Primary school students increased their knowledge about healthy nutrition and the importance of physical activity (p-value < 0.001). At the Obesity Pediatric Clinic, after 6 months, pre–post-intervention variation in their consumption of vegetables and fruit was +14% (p < 0.0001) and no variation in physical activity habits occurred (p = 0.34). In this group, the BMI z-score was not significantly decreased (−0.17 ± 0.63, p= 0.15). This study demonstrates the feasibility and efficacy of telematic tools and targeted community approaches in improving students’ knowledge with regard to healthy lifestyle, particularly in schools in suburbs with a high density of migrants and SES families. Comprehensive and integrated approaches provided to the obese patients remain mostly ineffective.

Patients with a prolonged disorder of consciousness (DoC) may present with severe spasticity and diffuse pain, which might impair motor output, thus preventing any possible behavioral responsiveness. A 26-year-old man affected by frontoparietal hemorrhage was operated by hematoma evacuation and decompressive craniectomy; coma persisted for 1 month; cranioplasty and ventriculo-peritoneal shunting was performed after 4 months. At admission in rehabilitation, he was diagnosed as vegetative state/unresponsive wakefulness syndrome (VS/UWS). The implantation of intrathecal baclofen (ITB) pump (Medtronic SynchroMed™ II), 14 months after, (60 μg/daily), dramatically improved behavioral responsiveness according to Coma Recovery Scale-Revised (CRS-R) from 6 to 12 (1 month after ITB). Nociception Coma Scale-Revised (NCS-R) also changed from 4 to 8 at the same time points. This case report may be an example of covert cognition that should have been diagnosed as a functional locked-in syndrome or motor-cognitive dissociation, rather than as VS/UWS.

Background: Severe acquired brain injury (sABI) encompasses a range of neurological impairments. Visual dysfunction, particularly homonymous visual field defects (HVFDs) and homonymous hemianopia (HH), commonly afflicts sABI survivors, affecting their cognitive and motor rehabilitation. This study presents the FunctionaL Assessment Scale of Hemianopia (FLASH), developed to analyze the most common postural behaviors exhibited by sABI patients with hemianopia during activities of daily living. A comparison to traditional static automated perimetry for diagnosing visual field deficits (VFDs) to determine the sensitivity and specificity of the FLASH was used. Additionally, this study also aimed to assess its reliability. Methods: Fifty-six patients (25 F, 31 M, mean age 60.59 ± 14.53) with strokes in the sub-acute phase (<6 months from the onset) were assessed with both FLASH and a Humphrey Field Analyzer. Results: After removing two items found to be less reliable than others, FLASH showed high sensitivity (81%) and specificity (77%) when compared to static automated perimetry. Inter-rater reliability was also high, with an intra-class correlation coefficient of 0.954, as well as the internal consistency computed by Cronbach’s alpha, equal to 0.874. Conclusion: FLASH could offer a valuable and cost-effective screening tool for VFD in sABI patients during neurorehabilitation, with potential implications for healthcare cost reduction.