Physical Activity in young female outpatients with BORderline personality Disorder (PABORD): a study protocol for a randomized controlled trial (RCT).

BACKGROUND: Current treatments for mental disorders, like pharmacotherapy or psychological approaches, do not lead to full remission in all individuals. Physical activity (PA) is effective at improving psycho-physical health in major depressive and anxiety disorders. However, the efficacy of PA as an adjunctive treatment for borderline personality disorder (BPD) has not been studied. To date, there are no approved pharmacological treatments for this severe condition and limited accessibility to effective psychotherapeutic interventions. This study tests the efficacy of a structured PA programme as an additional treatment for BPD outpatients. METHODS: The PABORD is a randomised controlled trial for female outpatients (18-40 years) with a BPD diagnosis. The intervention group (n = 32) will participate in a 12-week structured PA programme supervised by a sport medicine physician and preceded by three psychoeducation sessions on healthy eating habits. The control group (n = 32) will receive a 12-week psychoeducation programme on PA, diet, and health risks of a sedentary lifestyle for a total of 8 sessions. The study aims to determine if the PA intervention is superior to the control in reducing BPD symptoms. Secondary aims include improving PA levels and physical and psychological health. Assessments will be conducted at baseline, post-intervention, and 3 months post-intervention. DISCUSSION: The structured PA programme is expected to outperform the control group in terms of health and PA outcomes at the end of the intervention. Repeated assessments will also help to identify psychosocial factors that influence PA maintenance. Findings will support the potential widespread implementation of PA programmes for BPD treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT06461104. Registered on 6 June 2024 {2a}.

Circulating Serum Micro-RNA as Non-Invasive Diagnostic Biomarkers of Endometriosis.

BACKGROUND/OBJECTIVES: Endometriosis (END) is a painful gynecological condition. Clinical examination, imaging, and laparoscopy can provide a definitive diagnosis of END. Nonetheless, non-invasive biomarkers could help enhance and streamline the diagnostic process. Micro-RNAs (miRNAs), a family of small non-coding RNAs, could serve as useful non-invasive biomarkers for END. The aim of this study was to perform serum miRNA profiling in a retrospective cohort of women to identify miRNAs that are differentially expressed in END compared to control patients. METHODS: RNA was isolated from serum samples of 67 END patients and 60 control women. The expression profile of a 754-miRNA panel was studied with RT-qPCR performed on a QuantStudio 12K Flex with the TaqMan OpenArray miRNA panel. A Censored Regression Model was used for miRNA differential expression analysis. Several gene-enrichment algorithms were employed to identify pathways related to the target genes of differentially expressed miRNAs. RESULTS: One hundred and thirty miRNAs were detected in at least 75% of samples from either the END or the control group. Sixteen miRNAs were significantly modulated between the END and control groups. Enrichment analysis identified targets significantly overrepresented in numerous pathways involved in biological processes related to END, including inflammation, angiogenesis, cellular invasion, cell-cycle/cell proliferation, and estrogen and progesterone hormonal signaling. CONCLUSIONS: Our study indicates that differentially expressed miRNAs between END patients and controls can be identified through liquid biopsy. Our findings also suggest a potential role for serum miRNAs in the pathophysiology of END, warranting further investigations for their use as non-invasive biomarkers.

Burnout, working alliance, and ward atmosphere: A multisite study of mental health professionals and patients with schizophrenia.

This study examined the association between burnout, psychological distress, ward atmosphere, and working alliance (WA) among mental health workers treating patients with schizophrenia spectrum disorder (SSD). Data were collected from 345 patients with SSD and 151 mental health workers across 98 residential facilities (RFs) as part of the DiAPAson project from October 2020 to October 2021. Participants were excluded from the study if they exhibited patient-operator matching errors, dropped out, or had many missing Maslach Burnout Inventory (MBI) scores. The final sample included 282 patients and 155 healthcare workers. Burnout was assessed using the MBI. Psychological distress was evaluated with the 12-item version of the General Health Questionnaire. WA and ward atmosphere were evaluated with the WA Inventory and the Ward Atmosphere Scale, respectively, in both staff and patients. Sociodemographic and clinical data was also collected and analysed. Burnout was associated with a less supportive ward atmosphere, a weaker WA, and higher staff distress. Severe psychiatric symptoms evaluated with Brief Psychiatric Rating Scale in patients were also linked to staff burnout levels. Discrepancies in the perceptions of the ward atmosphere and the WA were observed between staff and patients, with patients reporting better perceptions in both domains. Our findings highlight the complex dynamics of well-being within psychiatric care settings, emphasizing the importance of role clarity, professional autonomy, and a positive ward atmosphere in mitigating burnout. Interventions focused on such factors may help support mental health professionals involved in SSD patient care. ISRCTN registry ID ISRCTN21141466.

Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial.

BACKGROUND: Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population. METHODS: This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and <75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m2 from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26). FINDINGS: Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed. INTERPRETATION: Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation. FUNDING: AbbVie and Johnson & Johnson.

Association of Weight Status and Waist Circumference with Physical Activity in people with Schizophrenia Spectrum Disorders and healthy controls.

BACKGROUND: Individuals with Schizophrenia Spectrum Disorders (SSD) often suffer from obesity and do limited Physical Activity (PA). PA has many beneficial effects on a variety of somatic and mental variables and it should be strengthened among people with mental disorders. The relationship between Body Mass Index (BMI), Waist Circumference (WC), and PA in this population is poorly understood, with a lack of precise PA assessment. This study investigates the association between BMI, WC, weight, and PA in individuals with SSD and controls using accelerometers. METHODS: One hundred twenty-six patients with SSD (residents and outpatients) and 110 sex- and age-matched controls were enrolled. Clinical, sociodemographic, and quality-of-life data were collected. PA was measured with a tri-axial ActiGraph GT9X and quantified by Vector Magnitude (VM). Relationships between PA and BMI, WC, and weight changes were analysed using linear regression models. RESULTS: Patients were more likely to be unmarried, unemployed, and less educated compared to controls (p < 0.001). Residents had more medical comorbidities (p = 0.001), while outpatients had higher BMI, weight, and WC (p < 0.001). Residents reported more severe psychopathology, lower functioning, and greater use of psychopharmacological medications (p < 0.001). Higher PA levels were not significantly associated with lower BMI, WC, or weight. Although not statistically significant, increased PA showed a trend towards lower obesity risk. CONCLUSIONS: Sociodemographic, medical, and clinical characteristics of individuals with SSD define vulnerability factors that can inform tailored interventions to improve PA.

Natural history of cerebral visual impairment in children with cerebral palsy.

AIM: To longitudinally evaluate the natural history of cerebral visual impairment (CVI) in children with cerebral palsy (CP) and identify which early visual signs or symptoms are associated with cognitive visual disorders (CVDs) at school age. METHOD: Fifty-one individuals with CP and CVI underwent an ophthalmological, oculomotor, and basic visual function evaluation at three time points: T0 (6-35 months old); T1 (3-5 years old); and T2 (≥6 years old). We also performed a cognitive visual evaluation at T2. Logistic regression fitted using a generalized estimation equation (binary) and cumulative link models (ordinal) were used to model the outcomes of interest. RESULTS: Ophthalmological deficits were stable over time, except for ocular fundus abnormalities (T1-T0, p = 0.01; T2-T1, p = 0.02; T2-T0, p < 0.01) and strabismus, whose frequency increased with age (T2-T0, p= 0.02 with T2-T0, p = 0.05). Conversely, fixation (T1-T0, T2-T0, p < 0.01), smooth pursuit (T2-T1, T2-T0, p < 0.01), saccades (T1-T0, T2-T1, T2-T0, p < 0.01), as well as visual acuity, contrast sensitivity, and visual field (T1-T0, T2-T0, p < 0.01) all improved over time. Early oculomotor dysfunction was associated with CVD at T2. INTERPRETATION: Although a diagnosis of CVI was confirmed in all children at each time point, several visual signs and symptoms improved over time; in some cases, they reached complete recovery at T1 and T2. These results emphasize the 'permanent' but 'not unchanging' nature of the CVI associated with CP during development.

Is precision medicine the solution to improve organ preservation in laryngeal/hypopharyngeal cancer? A position paper by the Preserve Research Group.

In locally advanced (LA) laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC), larynx preservation (LP) strategies aim at the cure of the disease while preserving a functional larynx, thus avoiding total laryngectomy and the associated impact on the quality of life. In the last decades, apart from transoral and open-neck organ preservation approaches, several non-surgical regimens have been investigated: radiotherapy alone, alternate, concurrent or sequential chemoradiation, and bioradiotherapy. Despite major progress, the identification of reliable and effective predictors for treatment response remains a clinical challenge. This review examines the current state of LP in LA-LHSCC and the need for predictive factors, highlighting the importance of the PRESERVE trial in addressing this gap. The PRESERVE trial represents a pivotal initiative aimed at finding the optimal therapy for laryngeal preservation specific to each patient through a retrospective analysis of data from previous LP trials and prospectively validating findings. The goal of the PRESERVE trial is to develop a comprehensive predictive classifier that integrates clinical, molecular, and multi-omics data, thereby enhancing the precision and efficacy of patient selection for LP protocols.

Guided versus freehand single implant placement: A 3-year parallel randomized clinical trial.

OBJECTIVES: The present parallel randomized clinical trial aimed to assess, after a 3-year follow-up period, whether the choice of surgical technique-either manual or guided-and of the operator - non-expert operator or skilled - can affect the stability of peri­implant marginal bone levels in implants placed 1 mm sub-crestal. MATERIALS AND METHODS: Patients received platform-switched implants (Anyridge, MegaGen Implant Co., Gyeongbuk, South Korea) featuring a 5-degree internal conical connection and supporting single screw-retained fixed crowns. The implants were randomly assigned to be placed through a digitally static guided surgery procedure (Test group - GS) or a freehand surgical technique (Control Group - FH). A non-expert operator (fewer than 20 implants placed in his professional activity) was selected to perform procedures for the GS Group, while a skilled operator (with over 1000 implants placed in his professional activity) was chosen for the FH Group. Marginal bone level (MBL) was measured at prosthesis installation (t0) and at 1 (t1), 2 (t2) and 3 years (t3) of follow-up. Changes in MBL from t0 to t3 were analyzed through periapical radiographs. Moreover, MBL changes at all time points were correlated to different supra-crestal soft tissue heights (STH): less than 3 and ≥ 3 mm, respectively. RESULTS: 60 implants in 18 patients were examined, with 30 implants allocated to the GS group and 30 to the FH group. The difference in MBL change between the two groups was 0.11 ± 0.22 mm, which was not statistically significant (p = 0.61). At the time of prosthetic loading, the mean MBL for implants with STH less than 3 mm was 0.33 mm higher than implants with STH ≥ 3 mm, though this difference was not statistically significant (P = 0.065). CONCLUSIONS: Digitally static guided implant placement, performed by a non-expert operator, does not limit marginal bone remodeling, when compared to a freehand procedure performed by an experienced operator. CLINICAL SIGNIFICANCE: After correct and careful planning, early marginal bone levels (MBL) around conical connection, platform-switched implants placed sub-crestally may be stable in time. Digital planning and surgery have the potential to assist non-expert clinicians in achieving implant placements with comparable outcomes to those performed by experts.

Effects of Limbs' Spasticity on Spinopelvic Alignment in Post-Stroke Patients: A Cross-Sectional Study.

Objectives: This study aimed to determine the impacts of upper and lower limb (UL and LL) spasticity and impairment on spinal alignment in chronic post-stroke patients. Methods: A total of 45 consecutive chronic post-stroke patients, 18 women and 27 men, from 18 to 70 years old who presented post-stroke hemiparesis were recruited in this cross-sectional study. The clinical assessment included the Modified Ashworth Scale (UL-MAS and LL-MAS spasticity), Upper Limb Motricity Index (UL-MI), FAST-UL, and Five Times Sit-to-Stand Test (5T-STS); the Associated Reaction Rating Scale was used to measure associated reactions in the hemiparetic UL, the plumb line distance from the spinous process of C7 on the sagittal (PL-C7s) and frontal plane (Pl-C7f), the kyphosis apex (PL-AK), and the spinous process of L3 (PL-L3). Angular measures of spinal alignment were measured by a Bunnell scoliometer™ (angle of trunk rotation-ATR) and a gravity-dependent inclinometer (inclination at C7-T1 and T12-L1). Results: In chronic post-stroke patients, there was found to be an association between the 5T-STS and PL-C7f (ß = 0.41, p = 0.05) and the angle of inclination at T12-L1 (ß = 0.44, p = 0.01). The FAST-UL correlated with PL-C7f (ß = -0.41, p = 0.05), while the UL-MI correlated with this last parameter (ß = -0.36, p = 0.04) and the ATR (ß = -0.31, p = 0.05). The UL-MAS showed correlation with the ATR (ß = 0.38, p = 0.01). Conclusions: The results lead to the possibility that, in chronic post-stroke patients, spinal misalignment on the frontal and sagittal plane is associated both with strength impairment and UL spasticity. The improvement or restoration of spinopelvic parameters can take advantage of therapeutic interventions targeted at motor improvement and spasticity reduction of the hemiparetic side.

Gender-Specific Differences in Spinal Alignment and Muscle Power in Patients with Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is an advancing neurodegenerative disorder characterized by spinal anomalies and muscular weakness, which may restrict daily functional capacities. A gender-focused examination of these effects could provide valuable insights into customized rehabilitation strategies for both sexes. PURPOSE: This study investigates the influence of spinal alignment on lower-limb function during the sit-to-stand (STS) movement in patients with Parkinson's disease compared to healthy individuals. METHODS: A cross-sectional study was conducted with 43 consecutive patients with PD (25 males and 18 females; average age 73.7 ± 7.1 years) and 42 healthy controls (22 males and 20 females; average age 69.8 ± 6.0 years). Assessments included the International Physical Activity Questionnaire (IPAQ), Hoehn and Yahr staging, and measurements of vertical deviations from several spinal landmarks. Lower-limb muscle power during the STS task was evaluated using the Muscle Quality Index (MQI). RESULTS: Both absolute (Watts) and relative (Watts/Kg) muscle power in the lower limbs were notably decreased in the PD group compared to the control group. Within the PD cohort, muscle power showed a negative relationship with age and a positive association with the degree of lumbar lordosis (PL-L3). Importantly, gender-specific analysis revealed that male patients with PD had significantly higher lower-limb muscle power compared to female patients with PD, highlighting the need for gender-tailored therapeutic approaches. CONCLUSIONS: The findings suggest that preserving lumbar lordosis is crucial for maintaining effective lower-limb muscle biomechanics in individuals with Parkinson's disease.

A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy.

BACKGROUND: Metal exposures can adversely impact olfactory function. Few studies have examined this association in children. Further, metal exposure occurs as a mixture, yet previous studies of metal-associated olfactory dysfunction only examined individual metals. Preventing olfactory dysfunctions can improve quality of life and prevent neurodegenerative diseases with long-term health implications. OBJECTIVE: We aimed to test the association between exposure to a mixture of 12 metals measured in environmental sources and olfactory function among children and adolescents residing in the industrialized province of Brescia, Italy. METHODS: We enrolled 130 children between 6 and 13 years old (51.5% females) and used the "Sniffin' Sticks" test to measure olfactory performance in identifying smells. We used a portable X-ray fluorescence instrument to determine concentrations of metals (arsenic (As), calcium, cadmium (Cd), chromium, copper, iron, manganese, lead (Pb), antimony, titanium, vanadium and zinc) in outdoor and indoor deposited dust and soil samples collected from participants' households. We used an extension of weighted quantile sum (WQS) regression to test the association between exposure to metal mixtures in multiple environmental media and olfactory function adjusting for age, sex, socio-economic status, intelligence quotient and parents' smoking status. RESULTS: A higher multi-source mixture was significantly associated with a reduced Sniffin' Sticks identification score (ß = -0.228; 95% CI -0.433, -0.020). Indoor dust concentrations of Pb, Cd and As provided the strongest contributions to this association (13.8%, 13.3% and 10.1%, respectively). The metal mixture in indoor dust contributed more (for 8 metals out of 12) to the association between metals and olfactory function compared to soil or outdoor dust. IMPACT STATEMENT: Among a mixture of 12 metals measured in three different environmental sources (soil, outdoor and indoor dust), we identified Pb, Cd and As measured in indoor dust as the main contributors to reduced olfactory function in children and adolescents residing in an industrialized area. Exposure to indoor pollution can be effectively reduced through individual and public health interventions allowing to prevent the deterioration of olfactory functions. Moreover, the identification of the factors that can deteriorate olfactory functions can be a helpful instrument to improve quality of life and prevent neurodegenerative diseases as long-term health implications.

Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol.

BACKGROUND: BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. METHODS: The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. DISCUSSION: BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. TRIAL REGISTRATION: ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.

Metabolic Syndrome in people treated with Antipsychotics (RISKMet): A multimethod study protocol investigating genetic, behavioural, and environmental risk factors.

INTRODUCTION: The RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design. METHOD: The RISKMet project investigates MetS in individuals treated with SGAs, focusing on both adult and paediatric populations. The study utilizes a case-control design to examine potential risk factors for MetS, categorizing participants as MetS+ considered as "Cases" and MetS- considered as "Controls" matched by sex and age. The evaluation of factors such as MetS, lifestyle habits, and environmental influences is conducted at two time points, T0 and T3, after 3 months. Subsequently, the project aims to assess body parameters, including physical examinations, and blood, and stool sample collection, to evaluate metabolic markers and the impact of SGAs. The analysis includes pharmacological treatment data and genetic variability. Behavioural markers related to lifestyle, eating behaviour, PA, and mood are assessed at both T0 and T3 using interviews, accelerometers, and a mobile app. The study aims to improve mental and physical well-being in SGA-treated individuals, establish a biobank for MetS research, build an evidence base for physical health programs, and develop preventive strategies for SGA-related comorbidities. CONCLUSIONS: This project innovates MetS monitoring in psychiatry by using intensive digital phenotyping, identifying biochemical markers, assessing familial risks, and including genetically similar healthy controls. STUDY REGISTRATION NUMBER: ISRCTN18419418 at www.isrctn.com.

The effect of weight gain and metabolic dysfunction-associated steatotic liver disease on liver fibrosis progression and regression in people with HIV.

OBJECTIVE: People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics. DESIGN: Multicenter cohort study. METHODS: Fibrosis progression was defined as development of significant fibrosis [liver stiffness measurement (LSM) ≥8 kPa], or transition to cirrhosis (LSM ≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM less than 8 kPa, or to LSM less than 13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multistate Markov model was used to describe transitions across fibrosis states. RESULTS: Among 1183 PWH included from three centers (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4 and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9-3.5), the incidence rate of fibrosis progression and regression was 2.8 [95% confidence interval (CI) 2.3-3.4] and 2.2 (95% CI 1.9-2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression [odds ratio (OR) 3.11, 95% CI 1.59-6.08], whereas weight gain (OR 0.30, 95% CI 0.10-0.84) and male sex (OR 0.32, 95% CI 0.14-0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain [adjusted hazard ratio (aHR) 3.12, 95% CI 1.41-6.90] and MASLD (aHR 2.72, 95% CI 1.05-7.02). CONCLUSION: Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy.

Xanthan-based chlorhexidine gel effects in non-surgical periodontal therapy? A meta-analysis.

OBJECTIVE: To carry out a systematic review and meta-analysis of randomized controlled clinical trials (RCTs) and controlled clinical trials (CCTs) comparing scaling and root planing (SRP) or placebo with subgingival application of xanthan-based CHX (chlorhexidine) gel as adjunct to SRP. MATERIALS AND METHODS: The literature search was carried out in PubMed/MEDLINE, EMBASE, and SCOPUS; primary outcomes were probing pocket depth (PPD) reduction and gain in clinical attachment level (CAL). RESULTS: Overall, 15 studies were included. Three studies were judged to be at moderate risk of bias while the remaining 12 were rated at high risk of bias. A significant improvement in PPD reduction (standardized mean difference, SMD, 0.87, 95% CI, 0.41-1.34) and CAL gain (SMD = 0.84, 95% CI, 0.36-1.33) emerged for the SRP + CXH gel compared to the SRP alone group, in the presence of significant high heterogeneity among the studies. CONCLUSIONS: Our systematic review and meta-analysis showed that xanthan-based chlorhexidine gel as adjunct to non-surgical periodontal therapy gives benefit in terms of PPD reduction and CAL gain as compared to non-surgical periodontal therapy only. Since there was high heterogeneity among studies and the quality of the evidence is low, further studies characterized by a better methodology, adequate sample size and longer follow-up are warranted in the next future. REGISTRATION: The protocol of this scoping review was registered in the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/PROSPERO) with ID: CRD42023391589.

The CDK Inhibitor Dinaciclib Improves Cisplatin Response in Nonseminomatous Testicular Cancer: A Preclinical Study.

BACKGROUND: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). METHODS: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. RESULTS: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. CONCLUSIONS: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.

Topical Antiseptics in Minimizing Ocular Surface Bacterial Load Before Ophthalmic Surgery: A Randomized Controlled Trial.

PURPOSE: To investigate the reduction of the ocular surface bacterial load induced by 2 commercially available ophthalmic antiseptic formulations, povidone-iodine (PVI) 0.6% and chlorhexidine (CLX) 0.02%, before ocular surgery. DESIGN: Randomized controlled trial. METHODS: Seventy adult patients undergoing intraocular surgery (phacoemulsification) were randomized to receive in the index eye PVI (group A) 4 times a day for 3 days or CLX (group B) 4 times a day for 3 days before surgery. The untreated eye was used as control. A conjunctival swab was taken in both eyes before (T0) and after (T1) therapy. Microbial DNA was quantified with real-time polymerase chain reaction (PCR) analysis. The Mick algorithm was used to compare the abundance of each genus/genera against the distribution of abundances from the reference. At T1, patients filled a questionnaire to evaluate therapy-induced symptoms. Primary outcome was the reduction of bacterial DNA at T1 (microbial load), vs control arm, expressed as mean number of real-time PCR cycle times (CTs). Secondary outcomes were taxonomic composition, differential abundance, and therapy-induced ocular symptoms. RESULTS: The T0-T1 difference in CT was significant in group B, but not in group A (mean [95% CI], 0.99 [0.33] vs 0.26 [0.15], P < .001, and 0.65 [0.3] vs 0.45 [0.41], P = .09, respectively). The taxonomic composition, alpha, and beta diversity remained consistent at all time points in both groups. The rate of patients reporting therapy-induced ocular symptoms and the mean discomfort grade were greater in group A than in group B (97% vs 26% and 4.97±2.48 vs 0.66±1.53, respectively). CONCLUSIONS: Compared with PVI 0.6%, CLX 0.02% induced a greater reduction of ocular surface bacterial load, with no significant alterations of the taxonomic composition. Moreover, CLX was better tolerated than PVI.

Stability of circulating miRNA in saliva: The influence of sample associated pre-analytical variables.

BACKGROUND AND AIMS: Increasing evidence supports the practicability of salivary cell-free (cf) miRNA as liquid biopsy markers in cancers. Its successful translation in the clinical setting requires reproducible approaches for saliva manipulation, in order to control for pre-analytical variables influencing miRNA stability. This study aims to define the optimal conditions to maintain the integrity of saliva during collection, transport and processing with respect to cf-miRNA quantification. MATERIALS AND METHODS: Saliva was collected from 20 healthy subjects and 8 oral cancer patients. Two sampling methods were tested and different storage temperatures and times were evaluated. Salivary expression level of target miRNAs was quantified by qPCR. Comparison between group mean values at specific conditions were performed using paired t-tests. Agreement between measurements was evaluated using a Bland-Altman plot. RESULTS: Different collection methods revealed comparable levels of salivary miR-484 and miR-106b-5p in both subject cohorts. MiRNAs were stable for up to 48 h at 4 °C in saliva supernatant, showing significant alteration after 96 h. Mid-term storage of supernatant at -20 °C decreased miRNA stability significantly compared to standard -80 °C. CONCLUSIONS: Cf-miRNA in saliva were slightly altered by collection methods and storage conditions, both in healthy and in pathological contexts, and remained stable for a period of time compatible with main clinical routine needs.

Electrophysiological neuromuscular alterations and severe fatigue predict long-term muscle weakness in survivors of COVID-19 acute respiratory distress syndrome.

Introduction: Long-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits. Methods: Muscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control. Results: MVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT. Discussion: Electrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.