Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure.

BACKGROUND AIMS: Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis characterized by multiple organ failure and high short-term mortality. The pathophysiology of ACLF involves elevated systemic inflammation leading to organ failure, along with immune dysfunction that heightens susceptibility to bacterial infections. However, it is unclear how these aspects are associated with recovery and non-recovery in ACLF. APPROACH RESULTS: Here we mapped the single-cell transcriptome of circulating immune cells from ACLF-, acute decompensated (AD) cirrhosis patients and healthy individuals. We further interrogate how these findings as well as immunometabolic- and functional profiles associate with ACLF recovery (ACLF-R) or non-recovery (ACLF-NR). Our analysis unveiled two distinct states of classical monocytes (cMon). Hereto, ACLF-R cMons were characterized by transcripts associated with immune- and stress tolerance, including anti-inflammatory genes such as RETN and LGALS1 . Additional metabolomic- and functional validation experiments implicated an elevated oxidative phosphorylation metabolic program as well as an impaired ACLF-R cMon functionality. Interestingly, we observed a common stress-induced tolerant state, oxidative phosphorylation program and blunted activation among lymphoid populations in ACLF-R patients. Conversely, ACLF-NR cMon featured elevated expression of inflammatory- and stress response genes such as VIM , LGALS2 , and TREM1 along with blunted metabolic activity and increased functionality. CONCLUSIONS: This study identifies distinct immuno-metabolic cellular states that contribute to disease outcome in ACLF patients. Our findings provide valuable insights into the pathogenesis of ACLF, shedding light on factors driving either recovery or non-recovery phenotypes which may be harnessed as potential therapeutic targets in the future.

Rapid and sustained improvements in itch and quality of life with upadacitinib plus topical corticosteroids in adults and adolescents with atopic dermatitis: 52-week outcomes from the phase 3 AD Up study.

Purpose: Atopic dermatitis (AD) adversely impacts quality of life (QoL). We evaluated the effect of upadacitinib, an oral selective Janus kinase inhibitor approved for moderate-to-severe AD, plus topical corticosteroids (+TCS) on patient-reported outcomes (PROs) over 52 weeks.Materials and methods: In the phase 3 AD Up study (NCT03568318), adults and adolescents with moderate-to-severe AD were randomized 1:1:1 to once-daily upadacitinib 15 mg, 30 mg, or placebo + TCS. Itch, skin pain/symptoms, sleep, QoL, daily activities, emotional state, mental health, and patient impressions of disease severity/improvement/treatment satisfaction were assessed.Results: This analysis included 901 patients. Within 1-2 weeks, PRO improvements were greater with both upadacitinib doses than with placebo (p <.05). Improvements increased through weeks 4-8; rates were generally maintained through week 52. At week 52, the proportion of patients with clinically meaningful improvements in itch (Worst Pruritus Numerical Rating Scale improvement ≥4), skin pain (AD Symptom Scale Skin Pain improvement ≥4), sleep (AD Impact Scale [ADerm-IS] Sleep improvement ≥12), daily activities (ADerm-IS Daily Activities improvement ≥14), and emotional state (ADerm-IS Emotional State improvement ≥11) ranged from 62.1%-77.7% with upadacitinib 15 mg + TCS and 71.3%-83.6% with upadacitinib 30 mg + TCS.Conclusions: Upadacitinib + TCS results in rapid, sustained improvements in burdensome AD symptoms and QoL.

Radiologic Lag and Brain MRI Lesion Dynamics During Attacks in MOG Antibody-Associated Disease.

BACKGROUND AND OBJECTIVES: Knowledge of the evolution of CNS demyelinating lesions within attacks could assist diagnosis. We evaluated intra-attack lesion dynamics in patients with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) vs multiple sclerosis (MS) and aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD). METHODS: This retrospective observational multicenter study included consecutive patients from Mayo Clinic (USA) and Great Ormond Street Hospital for Children (UK). Inclusion criteria were as follows: (1) MOGAD, MS, or AQP4+NMOSD diagnosis; (2) availability of ≥2 brain MRIs (within 30 days of attack onset); and (3) brain involvement (i.e., ≥1 T2 lesion) on ≥1 brain MRI. The initial and subsequent brain MRIs within a single attack were evaluated for the following: new T2 lesions(s); resolved T2 lesion(s); both; or no change. This was compared between MOGAD, MS, and AQP4+NMOSD attacks. We used the Mann-Whitney U test and χ2/Fisher exact test for statistical analysis. RESULTS: Our cohort included 55 patients with MOGAD (median age, 14 years; interquartile range [IQR] 5-34; female sex, 29 [53%]) for a total of 58 attacks. The comparison groups included 38 patients with MS, and 19 with AQP4+NMOSD. In MOGAD, the initial brain MRI (median of 5 days from onset [IQR 3-9]) was normal in 6/58 (10%) attacks despite cerebral symptoms (i.e., radiologic lag). The commonest reason for repeat MRI was clinical worsening or no improvement (33/56 [59%] attacks with details available). When compared with the first MRI, the second intra-attack MRI (median of 8 days from initial scan [IQR 5-13]) showed the following: new T2 lesion(s) 27/58 (47%); stability 24/58 (41%); resolution of T2 lesion(s) 4/58 (7%); or both new and resolved T2 lesions 3/58 (5%). Findings were similar between children and adults. Steroid treatment was associated with resolution of ≥1 T2 lesion (6/28 [21%] vs 1/30 [3%], p = 0.048) and reduced the likelihood of new T2 lesions (9/28 vs 18/30, p = 0.03). Intra-attack MRI changes favored MOGAD (34/58 [59%]) over MS (10/38 [26%], p = 0.002) and AQP4+NMOSD (4/19 [21%], p = 0.007). Resolution of ≥1 T2 lesions was exclusive to MOGAD (7/58 [12%]). DISCUSSION: Radiologic lag is common within MOGAD attacks. Dynamic imaging with frequent appearance and occasional disappearance of lesions within a single attack suggest MOGAD diagnosis over MS and AQP4+NMOSD. These findings have implications for clinical practice, clinical trial attack adjudication, and understanding of MOGAD pathogenesis.

Sleep Behaviors and the Shape of Subcortical Brain Structures in Children with Overweight/Obesity: A Cross-Sectional Study.

OBJECTIVES: To examine the relationship between sleep and subcortical brain structures using a shape analysis approach. METHODS: A total of 98 children with overweight/obesity (10.0 ± 1.1 y, 59 boys) were included in the cross-sectional analyses. Sleep behaviors (i.e., wake time, sleep onset time, total time in bed, total sleep time, sleep efficiency, and wakening after sleep onset) were estimated with wrist-worn accelerometers. The shape of the subcortical brain structures was acquired by magnetic resonance imaging. A partial correlation permutation approach was used to examine the relationship between sleep behaviors and brain shapes. RESULTS: Among all the sleep variables studied, only total time in bed was significantly related to pallidum and putamen structure, such that those children who spent more time in bed had greater expansions in the right and left pallidum (211-751 voxels, all p's <0.04) and right putamen (1783 voxels, p = 0.03). CONCLUSIONS: These findings suggest that more time in bed was related to expansions on two subcortical brain regions in children with overweight/obesity.

Diagnostic Utility of MOG Antibody Testing in Cerebrospinal Fluid.

OBJECTIVE: The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing. METHODS: We retrospectively identified patients for CSF MOG-IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG-IgG for testing including: controls, 282; serum MOG-IgG positive MOG antibody-associated disease (MOGAD), 74; serum MOG-IgG negative high-risk phenotypes, 73; serum false positive MOG-IgG with alternative diagnoses, 18. A live cell-based assay assessed CSF MOG-IgG positivity (IgG-binding-index [IBI], ≥2.5) using multiple anti-human secondary antibodies and end-titers were calculated if sufficient sample volume. Correlation of CSF MOG-IgG IBI and titer was assessed. RESULTS: The pan-IgG Fc-specific secondary was optimal, yielding CSF MOG-IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG-IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG-IgG positive MOGAD patients; and 9/73 (12%) serum MOG-IgG negative patients with high-risk phenotypes. Serum negative but CSF positive MOG-IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG-IgG low-positives revealed CSF MOG-IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG-IgG (3/15[20%]) (p = 0.01). CSF MOG-IgG IBI and CSF MOG-IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001). INTERPRETATION: CSF MOG-IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG-IgG, and those with low positive serum MOG-IgG results and diagnostic uncertainty. These findings support a role for CSF MOG-IgG testing in the appropriate clinical setting. ANN NEUROL 2024.

Exploring the Nutritional and Bioactive Potential of Olive Leaf Residues: A Focus on Minerals and Polyphenols in the Context of Spain's Olive Oil Production.

Lyophilized plant-origin extracts are rich in highly potent antioxidant polyphenols. In order to incorporate them into food products, it is necessary to protect these phytochemicals from atmospheric factors such as heat, light, moisture, or pH, and to enhance their bioavailability due to their low solubility. To address these challenges, recent studies have focused on the development of encapsulation techniques for antioxidant compounds within polymeric structures. In this study, lyophilized olive leaf extracts were microencapsulated with the aim of overcoming the aforementioned challenges. The method used for the preparation of the studied microparticles involves external ionic gelation carried out within a water-oil (W/O) emulsion at room temperature. HPLC analysis demonstrates a high content of polyphenols, with 90% of the bioactive compounds encapsulated. Meanwhile, quantification by inductively coupled plasma optical emission spectroscopy (ICP-OES) reveals that the dried leaves, lyophilized extract, and microencapsulated form contain satisfactory levels of macro- and micro-minerals (calcium, potassium, sodium). The microencapsulation technique could be a novel strategy to harness the polyphenols and minerals of olive leaves, thus enriching food products and leveraging the antioxidant properties of the polyphenolic compounds found in the lyophilized extract.

Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies.

OBJECTIVE: To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults. DESIGN: Overview of systematic reviews. DATA SOURCE: Five bibliographic databases were searched from January 2002 to March 2024. RESULTS: From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose-response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%-17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose-response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations. CONCLUSION: We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.

DRI Triton SS-OCT applied to detect choroidal nodules in paediatric patients affected by NF1.

Purpose: To examine whether image processing of non-mydriatic DRI Triton SS-OCT (Topcon Corporation, Tokyo, Japan) using the red free filter could assess the presence of choroidal nodules and thus include their detection as a diagnostic criterion in neurofibromatosis type 1 (NF1). Material and methods: We included 417 eyes from 210 patients, 377 - from 190 patients diagnosed with NF1 according to the criteria established by the National Institutes of Health Consensus Development Conference (NIH) and 40 from 20 healthy patients as a control group. The mean age was 9.4 years (range 2 years-18 years). All patients had their visual acuity measured by a test according to age, were examined for the presence of lisch nodules and an Optical Coherence Tomography (OCT) of the macular area was performed. All the OCT images were analysed to check if visible nodules could be identified. Results: Ages 14 (95% CI=(9.7,18.3)) and 12 years (95% CI=(9.1,14)) are the cut-off points that best separate those with choroidal nodules with Triton OCT and lisch with slit lamp, respectively, from those without. lisch nodules were detected in 50% of cases of NF1 patients. The presence of choroidal nodules did not present a statistically significant correlation with the occurrence of optic pathway glioma (p = 0.96) nor with the patient's visual worsening (p = 0.072). A statistically significant correlation was observed between the presence of choroidal nodules and the presence of lisch nodules (p < 0.05). Conclusion: The Topcon Triton OCT red free tool would not be a good tool to detect choroidal nodules in patients with NF1 because of its low sensitivity. If the presence of choroidal nodules were to be included in the diagnostic criteria for NF1, it would be convenient to use a device with red and infrared radiations.

Choosing T-cell sources determines CAR-T cell activity in neuroblastoma.

Introduction: The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2. Methods: We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines. Results: The IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h. Conclusion: CB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.

Gut microbiota and its relationship with early vascular ageing in a Spanish population (MIVAS study).

BACKGROUND: Gut microbiota and its by-products are increasingly recognized as having a decisive role in cardiovascular diseases. The aim is to study the relationship between gut microbiota and early vascular ageing (EVA). METHODS: A cross-sectional study was developed in Salamanca (Spain) in which 180 subjects aged 45-74 years were recruited. EVA was defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), cardio-ankle vascular index (CAVI) or brachial-ankle pulse wave velocity (ba-PWV) above the 90th percentile of the reference population. All other cases were considered normal vascular ageing (NVA). MEASUREMENTS: cf-PWV was measured by SphygmoCor® System; CAVI and ba-PWV were determined by Vasera 2000® device. Gut microbiome composition in faecal samples was determined by 16S rRNA Illumina sequencing. RESULTS: Mean age was 64.4 ± 6.9 in EVA group and 60.4 ± 7.6 years in NVA (p < .01). Women in EVA group were 41% and 53% in NVA. There were no differences in the overall composition of gut microbiota between the two groups when evaluating Firmicutes/Bacteriodetes ratio, alfa diversity (Shannon Index) and beta diversity (Bray-Curtis). Bilophila, Faecalibacterium sp.UBA1819 and Phocea, are increased in EVA group. While Cedecea, Lactococcus, Pseudomonas, Succiniclasticum and Dielma exist in lower abundance. In logistic regression analysis, Bilophila (OR: 1.71, 95% CI: 1.12-2.6, p = .013) remained significant. CONCLUSIONS: In the studied Spanish population, early vascular ageing is positively associated with gut microbiota abundance of the genus Bilophila. No relationship was found between phyla abundance and measures of diversity.

"I'm Not Only a Body": Change in Thoughts about the Body after Mirror Exposure Treatment in Women with Obesity-An Exploratory Study.

Nowadays, obesity (OB) is one of the most important health problems in population-wide health. In addition to its physical consequences, it is a risk factor for the development of psychological problems, including body dissatisfaction (BD). This is why the treatment of BD is essential for its prevention. However, this has mostly been studied from a quantitative perspective, without focusing on the discomfort experienced by the person and the accompanying thoughts and emotions. In this study, 26 women with obesity (BMI > 30 kg/m2) participated, of whom 16 had high BD and 10 had low BD, as measured by the BSQ questionnaire. The women with high BD underwent six sessions of exposure to their own body in front of a mirror, recording the discomfort experienced with this vision during the session. In addition, all participants recorded positive and negative thoughts towards their body before and after these sessions. After the exposure treatment sessions, a reduction in symptomatology (BD, discomfort when visualizing one's own body) was observed, as well as a change in the thoughts expressed by the participants, both in quantity (fewer negative thoughts) and in quality (a more positive self-perception and/or in more respectful terms used towards themselves). In conclusion, such treatments prove to be effective in reducing subjective discomfort and body-related thoughts in women with obesity.

Sex Differences in Effects of Exercise on Physical Function in Aging: A Systematic Review with Meta-Analysis.

PURPOSE: Our objective was to synthesize and determine whether there are sex differences in physical function following exercise interventions in older adults. MATERIALS AND METHODS: A systematic search was conducted in four databases from inception to July 8th, 2023 searching for prospective trials that conducted exercise interventions in older adults and results for physical function were reported by sex. Pooled standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were estimated using a randomeffects method. The Sidik-Jonkman estimator was used to calculate the variance of heterogeneity (I²). RESULTS: A total of 19 studies involving 20,133 older adults (mean age ≥60 years, 33.7% female) were included. After exercise interventions, males reported significantly greater pre-post changes compared to females for upper body strength (SMD=-0.40, 95% CI: -0.71 to -0.09; I²=75.6%; n=8), lower body strength (SMD=-0.32, 95% CI: -0.55 to -0.10; I²=52.0%; n=11), and cardiorespiratory fitness (SMD=-0.29, 95% CI: -0.48 to -0.10; I²=89.1%; n=12). Conversely, the pooled SMDs showed a significant effect favoring females for motor fitness (SMD=0.21, 95% CI: 0.03 to 0.39; I²=0%; n=7). Limited and inconsistent results were observed for flexibility. CONCLUSIONS: Our study suggests the existence of sex-related differences on physical function after an exercise intervention in the older population.

Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Relationship between addictions and obesity, physical activity and vascular aging in young adults (EVA-Adic study): a research protocol of a cross-sectional study.

Background: Behavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years. Methods: This cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18-34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18-34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230® impedance meter. For physical activity and sedentary time, we will use the Actigraph® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury. Discussion: Addictions are on the rise in today's society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05819840].

The synkinetic mentalis muscle and its negative effect on the smile: pathomechanism and treatment with mentalis targeted selective neurectomies.

BACKGROUND: The treatment of post-paretic facial synkinesis is based on a combination of nonsurgical and surgical strategies. Even if improvements towards the restoration of a natural smile have been obtained with selective neurectomies (SN) and depressor anguli oris (DAO) myectomy, the lower lip frequently remains asymmetric and cranially displaced. The aim of this study was to evaluate the effect of the mentalis muscle on the position and symmetry of the lower lip in patients with synkinesis and to assess the added benefit of neurectomies of nerves innervating the mentalis muscle in improving the lower lip configuration and mandibular teeth show. METHODS: A retrospective cohort study on all patients affected by post-paretic synkinesis at our Institution was performed. A Non-mentalis Neurectomy Group including twelve patients treated with SN without targeting the branches to mentalis muscle was compared to a Mentalis Neurectomy Group, including sixteen patients who underwent additional specific mentalis branches neurectomies. All patients underwent DAO myectomy. Analyses of standardized images were performed with ImageJ software. RESULTS: Post-operative comparisons between the two groups showed superior and significant improvements in the Mentalis Neurectomy Group across all measures, including lower and upper border deviation (p=0.035 and p=.004, respectively), inclination of the lower lip (p=.019), and lower quadrant dental show (p=.004). CONCLUSIONS: The addition of targeted selective neurectomies to the branches innervating mentalis muscle significantly improved dental show and caudal position and symmetry of the lower lip during open mouth smile.

Post-Paretic Synkinesis: Objective & Subjective Comparisons of Depressor Anguli Oris (DAO) Myectomies vs DAO & Buccinator Myectomies.

BACKGROUND: Muscles affected by post-paretic synkinesis have imbalanced tonicity that limit peri-oral mimetic movement and inhibit the ability to smile. The depressor anguli oris (DAO) muscle has been a common myectomy target for the treatment of peri-oral synkinesis. While addition of buccinator myectomies to DAO myectomies has risen, no studies have analyzed the effects of buccinator myectomies. The goal of this study was to evaluate and compare the effects of a DAO myectomy with and without concomitant buccinator myectomy through objective facial metrics and subjective patient reported outcomes. METHODS: This study is a retrospective review of patients with post-paretic synkinesis who underwent DAO myectomy (DAO myectomy group) or DAO myectomy with buccinator myectomy (DAO+Buccinator myectomies group). Outcomes included post-operative differences in objective smile measures (smile angle, excursion, and dental show) using validated software, and patient reported outcomes using the Facial Disability Index (FDI) questionnaire and a myectomy-specific questionnaire. RESULTS: After chart review, 18 patients were included in the DAO myectomy group and 19 in the DAO+Buccinator myectomies group. There were no significant post-operative differences between the groups in 1. smile excursion, angle, or dental show at resting, closed smile, or open smile (p>.05), 2. FDI physical and social scores, p=.198 and p=.932, respectively, or 3. myectomy-specific questionnaire responses (p>.05). CONCLUSION: The addition of a buccinator myectomy to a DAO myectomy does not provide significant clinical benefit when compared with an isolated DAO myectomy, based on objective measures and subjective patient reported outcomes.

Evaluation of the efficacy of probiotics as treatment in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a gastrointestinal functional disorder mainly characterised by abdominal pain, bloating and altered bowel habits. Dysbiosis might seem to be involved in the pathogenesis of the disease. Probiotics represent a potential treatment, since these could favour the functional microbiota and improve symptoms. The aim was to review the effectiveness of the use of probiotics in IBS symptomatology, analysing the influence of duration and dose. 18 articles were included. At the individual level, Lactobacillus, Bifidobacterium and Bacillus could be useful in the treatment of symptoms. Bifidobacterium bifidum reported the best results (1 × 109 CFU/day for 4 weeks). The most effective combination was 2 Lactobacillus strains, one of Bifidobacterium and one of Streptococcus (4 × 109 CFU/day for 4 weeks). Future clinical trials should confirm these results and analyse the difference between individual and combined treatments.

Effect of Lower Extremity Nerve Decompression in Patients with Painful Diabetic Peripheral Neuropathy: The DNND Randomized, Observation Group- and Placebo Surgery-controlled Clinical Trial.

OBJECTIVE: Evaluate the effect of nerve decompression on pain in patients with lower extremity painful Diabetic Peripheral Neuropathy (DPN). SUMMARY BACKGROUND DATA: Currently, no treatment provides lasting relief for patients with DPN. Benefits of nerve decompression remain inconclusive. METHODS: This double-blinded, observation- and same-patient sham surgery-controlled randomized trial enrolled patients aged 18-80 years with lower extremity painful DPN who failed one-year of medical treatment. Patients were randomized to nerve decompression- or observation-group (2:1). Decompression-group patients were further randomized and blinded to nerve decompression in either right or left leg and sham surgery in the opposite leg. Pain (11-point Likert score) was compared between decompression and observation groups and between decompressed versus sham legs at 12 and 56 months. RESULTS: Of 2987 screened patients, 78 were randomized. At 12 months, compared with controls (n=37), both right-decompression-group (n=22) and left-decompression-group (n=18) reported lower pain (mean difference for both, -4.46; [95% CI, -6.34 to -2.58 and -6.48 to -2.45 respectively]; P<0.0001). Decompressed and sham legs equally improved. At 56 months, compared with controls (n=14), pain was lower in both the right-decompression-group (n=20) (mean difference, -7.65; [95% CI, -9.87 to -5.44]; P<0.0001) and left-decompression-group (n=16) (mean difference, -7.26; [95% CI, -9.60 to -4.91]; P<0.0001). Mean pain score was lower in decompressed versus sham legs (mean difference, 1.57 [95% CI, 0.46 to 2.67]; P=0.0002). CONCLUSION: Although nerve decompression was associated with reduced pain, the benefit of surgical decompression needs further investigation since a placebo effect may be responsible for part or all of these effects.

Polyetheretherketone Implant Cranioplasty for Large Cranial Defects: A Seven-Year Follow-Up.

BACKGROUND: Goals of a cranioplasty include protection of the brain, restoration of normal appearance, and neurological function improvement. Although choice of materials for cranial remodeling has changed through the years, computer-designed polyetheretherketone (PEEK) implant has gained traction as a preferred material used for cranioplasty. However, long-term outcomes and complications of PEEK implants remain limited. The goal of this study was to report long-term clinical outcomes after PEEK implant cranioplasty. METHODS: A retrospective chart review was performed on patients undergoing PEEK cranioplasty between January 2007 and February 2023. Preoperative, intraoperative, and postoperative data were collected and analyzed. RESULTS: Twenty-two patients were included in this study. Mean postoperative follow-up time was 83.45 months (range: 35.47-173.87). Before PEEK implant cranioplasty, patients with multiple cranial procedures had undergone a mean of 2.95 procedures. PEEK implant cranioplasty indications were prior implant infection (14) and secondary reconstruction of cranial defect (8). The mean implant size was 180.43 cm2 (range: 68.00-333.06). Four patients received a 2-piece implant. Postoperative complications included: perioperative subgaleal self-resolving fluid collection in 1 patient, hematoma in another, and 3 infections resulting in explantations with successful reinsertion in 2 patients. Four of 5 patients with preoperative history of seizures reported improved seizures and all 4 patients with preoperative syndrome of the trephined reported improved symptoms and neurological function. CONCLUSION: At a mean follow-up of 7 years, most PEEK implants continued to provide protection to the brain and consistent symptom relief in patients suffering from prior postcraniectomy/craniotomy sequelae of seizures and syndrome of the trephined.

Plant metabolic response to stress in an arid ecosystem is mediated by the presence of neighbors.

Plant neighbors in arid environments can ameliorate abiotic stress by reducing insolation, but they also attract herbivores and pathogens, especially when neighbors are close relatives that share similar antagonists. Plants' metabolic profiles provide a chemical fingerprint of the physiological processes behind plant responses to different environmental stresses. For example, abscisic acid and proline, mainly involved in stomatal closure and osmotic adjustment, can induce plant responses to abiotic stress, while jasmonic acid and salicylic acid primarily regulate plant defense to herbivory or pathogens. Neighbor plants can generate contrasting ecological contexts, modulating plant responses to abiotic and biotic stresses. We hypothesize that plant metabolic profile is modulated by its neighbors in a vegetation patch, expecting a higher investment in metabolites related to biotic-stress tolerance (i.e., herbivory or pathogens) when growing associated with other plants, especially to phylogenetically close relatives, compared to plants growing alone. We show that plants from five species growing with neighbors invest more in biotic-stress tolerance while their conspecifics, growing alone, invest more in abiotic-stress tolerance. This tendency in plants' metabolic profiles was not affected by the phylogenetic diversity of their neighborhood. Linking physiological snapshots with community processes can contribute to elucidating metabolic profiles derived from plant-plant interactions.