Pharmacological management of secondary chronic spinal cord injury: a systematic review.

INTRODUCTION: Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. SOURCE OF DATA: Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. AREAS OF AGREEMENT: Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. AREAS OF CONTROVERSY: The management of secondary chronic SCI is challenging, with unpredictable outcomes. GROWING POINTS: Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. AREAS TIMELY FOR DEVELOPING RESEARCH: Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.

The patients' perspective: cut off points for satisfaction in pharmacological therapy and surgical outcomes.

Background: This article presents the results of a pilot study investigating patients' satisfaction thresholds for pharmacological outcomes versus surgical outcomes. Materials and methods.: A total of 150 participants were presented with two hypothetical scenarios depicting either pharmacological therapy or surgical interventions. Each scenario described a potential outcome, from a 10% clinical improvement (value 10) to a 100% clinical improvement (value 100) and asked participants to indicate the satisfactory level they would find acceptable. Conclusions: The results revealed distinct patterns in satisfaction thresholds between the two treatment modalities. Between the 150 participants, 52,7% were male and 47,3% female. We also identified a total of 28,8% whom were healthcare workers. Overall, the results for the pharmacological therapy outcomes observed a mean of 60,88 with a standard deviation of 22,77, a median of 60 and a mode of 70; while for the surgical outcomes the mean was 67,81 with a standard deviation of 23,03, the median 85 and the mode 80. We also observed that for the pharmacological therapy outcomes healthcare workers had a lower satisfactory cut off compared to non-healthcare workers. Another interesting finding was that for pharmacological therapy outcomes individuals under 50 y/o had a higher satisfactory cut off compared to individuals over 50 y/o, while for the surgical outcomes we got opposite results. Overall, the findings of this pilot study, even if limited, demonstrated higher minimum satisfaction expectations for surgical outcomes compared to pharmacological therapy outcomes. Specifically, participants tended to require more favorable results and outcomes from surgical interventions to meet their minimum satisfaction criteria.

DGAT1 and DGAT2 Inhibitors for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Management: Benefits for Their Single or Combined Application.

Inhibiting diacylglycerol acetyltransferase (DGAT1, DGAT2) enzymes (iDGAT1, iDGAT2), involved in triglyceride (TG) synthesis, improves hepatic steatosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients. However, their potential synergism in disease onset (SLD) and progression (metabolic dysfunction-associated steatohepatitis, fibrosis) has been poorly explored. We investigated iDGAT1 and iDGAT2 efficacy, alone or combined (iDGAT1/2) on fat accumulation and hepatocellular injury in hepatocytes (HepG2) and on fibrogenic processes in hepatic stellate cells (LX2). We further tested whether the addition of MitoQ antioxidant to iDGAT1/2 would enhance their effects. SLD and MASH conditions were reproduced in vitro by supplementing Dulbecco's Modified Eagle's Medium (DMEM) with palmitic/oleic acids (PAOA) alone (SLD-medium), or plus Lipopolisaccaride (LPS), fructose, and glucose (MASH-medium). In SLD-medium, iDGAT1 and iDGAT2 individually, and even more in combination, reduced TG synthesis in HepG2 cells. Markers of hepatocellular damage were slightly decreased after single iDGAT exposure. Conversely, iDGAT1/2 counteracted ER/oxidative stress and inflammation and enhanced mitochondrial Tricarboxylic acid cycle (TCA) and respiration. In HepG2 cells under a MASH-like condition, only iDGAT1/2 effectively ameliorated TG content and oxidative and inflammatory mediators, further improving bioenergetic balance. LX2 cells, challenged with SLD/MASH media, showed less proliferation and slower migration rates in response to iDGAT1/2 drugs. MitoQ combined with iDGAT1/2 improved cell viability and dampened free fatty acid release by stimulating ß-oxidation. Dual DGAT inhibition combined with antioxidants open new perspectives for MASLD management.

[Psychiatric symptoms of Huntington's disease]. / Psychiatrische Symptome der Huntington-Krankheit.

Huntington's disease (HD) is an autosomal dominant inherited disease, which leads to motor, cognitive and psychiatric symptoms. The diagnosis can be confirmed by genetic testing for extended CAG repeats in the Huntingtin gene. Mental and behavioral symptoms are common in HD and can appear several years before the onset of motor symptoms. The psychiatric symptoms include apathy, depression, anxiety, obsessive-compulsive symptoms and, in some cases, psychoses and aggression. These are currently restricted to symptomatic treatment as disease-modifying treatment approaches are still under investigation. The current clinical practice is based on expert opinions as well as experience with the treatment of similar symptoms in other neurological and mental health diseases. This article provides an overview of the complex psychiatric manifestations of HD, the diagnostic options and the established pharmacological and nonpharmacological treatment approaches.

Prolactinoma: Navigating the Dual Challenge of Side Effects and Treatment Strategies - A Comprehensive Review.

This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma's clinical complexities and therapeutic nuances to guide optimal patient care strategies.

Psychotherapeutic interventions for depressive symptoms in older adults in a community setting: a systematic review protocol.

Depression is a prevalent illness among the elderly, so psychotherapeutic interventions are needed to promote health and quality of life. This literature review aims to identify trials of any psychotherapeutic interventions aimed at reducing depressive symptoms in older adults. A systematic literature review with a meta-analysis will be carried out. The following databases will be searched: CINAHL Plus with Full Text, MedicLatina, MEDLINE with Full Text, and Psychology and Behavioral Sciences Collection. To minimize bias, four reviewers will independently assess the inclusion of studies. The fifth reviewer will be responsible for disaggregating inclusion and exclusion between two authors. The results of the analysis will be grouped in a table with the characteristics of the included studies, including author, year, sample, objectives, methods, assessment instruments, psychotherapeutic interventions, results, follow-up and a data compilation scheme. This scientific article is a systematic review protocol for which the data has already been extracted and is being analyzed. Examples of possible strategies to include cognitive restructuring and mental health programs for older adults in community settings. With this clear and direct identification of psychotherapeutic interventions, it will be clearer for mental health professionals to be able to intervene effectively to promote the mental health and well-being of older adults. PROSPERO registration number: CRD42023449190.

Comparative effectiveness of non- pharmacological treatments in patients with persistent postural-perceptual dizziness: a systematic review and effect sizes analyses.

Introduction: The patho-psychological mechanisms of persistent postural-perceptual dizziness (PPPD) appear to be very complex, and a multimodal, multidisciplinary approach is suggested for treating patients with PPPD. The aim of this review was to provide a comprehensive overview of non-pharmacological treatments and their comparative effectiveness in patients with PPPD. Methods: Scopus, Web of Science, PsycINFO, Medline, Embase, CINAHL, Cochrane Library and ClinicalTrials.gov were searched in April 2022 with a search update in August 2023. Only randomized controlled trials (RCTs) were included. There was no restrictions regarding publication date. Two reviewers independently identified eligible trials, extracted data, double-checked all extracted information from the included articles and assessed the risk of bias using the Cochrane risk of bias tool. A qualitative synthesis was performed, considering methodological heterogeneity between trials. Finally, an effect size analysis was performed for each treatment comparison. The standardized mean differences (SMD) and their corresponding 95% confidence intervals (95%CI) were calculated for each trial using Review Manager 5.4. Results: Thirteen RCTs (618 patients with moderate or mild dizziness) out of 1,362 references describing seven different non-pharmacological comparisons were selected. Nine trials included patients with PPPD, and four trials included patients with functional dizziness. The trials used different interventions that were classified as: (1) psychotherapeutic interventions (cognitive behavioral therapy, patient education), (2) physiotherapeutic interventions/training (vestibular rehabilitation, optokinetic stimulation), (3) stimulation procedures (vagus nerve stimulation, transcranial direct current stimulation) and (4) device application (visual desensitization using personalized glasses). However, most of the trials investigated the effects of single interventions, rather than multimodal interdisciplinary treatment of patients with PPPD. The SMD for dizziness handicap and severity was between 0.04 and 0.52 in most trials. In one trial using visual desensitization, the SMD was 1.09 (strong effect on the severity of dizziness) and 1.05 (strong effect on dizziness handicap). Discussion: Several individual interventions have shown benefits in the treatment of patients with PPPD with small to moderate effects. However, the multimodal treatment or a combination of vestibular rehabilitation with visual desensitization, cognitive behavioral therapy including patient education, and medication support should be further investigated. Future trials should include a large sample size with severe dizziness, and provide a longer follow-up period. Clinical trial registration: PROSPERO CRD42022320344.

Clinical Intervention Strategies and Family Dynamics in Adolescent Eating Disorders: A Scoping Review for Enhancing Early Detection and Outcomes.

Background: This systematic review investigated the impact of familial factors on individuals aged 10-17 who have clinical signs or symptoms of eating disorders. Simultaneously, it scrutinized the involvement of the family in therapy, as well as other forms of intervention. Methods: The PsycINFO, PubMed, and Scopus databases were used to search for research material comprehensively. After applying specific criteria, 46 articles were deemed suitable and included in the systematic review. The study comprised a cohort of 4794 adolescents who received a diagnosis of either Anorexia Nervosa (AN), Bulimia Nervosa (BN), or Binge-Eating Disorder (BED). In addition, controls were utilized for 1187 adolescents, 1563 parents, 1809 siblings, and 11 other relatives. Results: The connection between family factors and eating disorders is primarily determined by the families' level of functioning, satisfaction with the family dynamic, parents' attitudes toward their children, and the role of food within the family system. Family Therapy was the most used psychotherapeutic approach in the treatment of AN. The incidence of reports in BN closely paralleled that of Cognitive-Behavioral Therapy (CBT) models. Articles about (Enhanced) CBT were exclusively associated with BED. Conclusions: Family-based approaches are crucial in comprehending, preventing, and addressing eating disorders in adolescents. Incorporating the study of family dynamics and actively engaging families in the treatment process can significantly enhance recovery rates and decrease the occurrence of relapses.

HPV Infections-Classification, Pathogenesis, and Potential New Therapies.

To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.

Advances in GPCR-targeted drug development in dermatology.

Achieving the efficacy and specificity of G-protein-coupled receptor (GPCR) targeting-drugs in the skin remains challenging. Understanding the molecular mechanism underlying GPCR dysfunction is crucial for developing targeted therapies. Recent advances in genetic, signal transduction, and structural studies have significantly improved our understanding of cutaneous GPCR functions in both normal and pathological states. In this review, we summarize recent discoveries of pathogenic GPCRs in dermal injuries, chronic inflammatory dermatoses, cutaneous malignancies, as well as the development of potent potential drugs. We also discuss targeting of cutaneous GPCR complexes via the transient receptor potential (TRP) channel and structure elucidation, which provide new opportunities for therapeutic targeting of GPCRs involved in skin disorders. These insights are expected to lead to more effective and specific treatments for various skin conditions.

Application of virtual reality to enhance therapeutic Tai Chi for depression in elderly people.

The battle against depression in the elderly is crucial due to its significant impact on their quality of life, physical and cognitive health, increased risk of social isolation and suicide, as well as the associated higher healthcare costs. This research investigates the effects of traditional and augmented reality Tai Chi, using the virtual environment "Managed Tai Chi," on depression in elderly individuals. The study involved 300 participants aged over 60 from the Beijing Medical Center, with an experimental period lasting six months and sessions held once a week. The Geriatric Depression Scale (GDS) was utilized as a diagnostic tool at the pre-test and post-test stages. The findings revealed that the VR group exhibited a more substantial reduction in depression compared to the traditional and control groups (p ≤ 0.05), indicating the enhanced efficacy of Tai Chi with VR augmentation in treating depression in the elderly.

Surgical and pharmacological treatment of childhood obesity.

The increase in obesity prevalence has been slowing down in numerous countries recently. WHO Europe has organized surveillance of childhood obesity (Childhood Obesity Surveillance Initiative, COSI) since 2008, which observed the prevalence of overweight and obesity of 6-9-year-old children is followed during this study and proved this result. The study Children's Health 2016 showed that after a period of the global increase of obesity until 2011, there was in the Czech Republic a period of certain stabilization, in which there weren´t major changes in weight. Unfortunately, the covid pandemic changed this trend and the current data from 2021 showed in the Czech Republic a serious increase in childhood obesity. For these children will be necessary to use a new type of treatment of obesity as a surgical and pharmacological specific treatment.

Lipid nanoparticle: advanced drug delivery systems for promotion of angiogenesis in diabetic wounds.

Diabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing.

The Management of Knee Osteoarthritis in the Real World: An Italian National Survey.

Background: Knee osteoarthritis is a degenerative and inflammatory disease causing pain and worsening patients' quality of life. Various conservative treatment options exist, but a gap between scientific evidence and clinical practice is still present. The aim of this prospective multicenter observational study is to describe the real outpatient territorial management of patients with knee osteoarthritis and to analyze the correlation between the anthropometric and clinical characteristics of the population of patients suffering from symptomatic knee osteoarthritis who were screened in the national survey. Methods: The educational national project was divided into three modules: the first and the last through webinars; and the second held in daily practice. The participants had to register structured observations, which were then stored in a national database and analyzed in order to identify correlations. The subgroups were stratified by body composition, radiological severity of knee osteoarthritis, pain, and functional ability. Results: The project has been joined by 155 physicians, and 2.656 observations about real-world outpatients being treated for knee osteoarthritis in Italy were collected. Data relating to real-world pharmacological and rehabilitation therapies in correlation with body composition, the radiological severity of knee osteoarthritis, pain, and functional ability were reported. Conclusions: Currently, there are no standardized protocols using effective combinations of therapeutic exercises, physical agents, and medications to control the progression of knee osteoarthritis. This real-word national survey proved to be useful for describing the current state of the art of therapeutic management of knee osteoarthritis and for emphasizing the need to fill the gap between scientific evidence and clinical practice.

[Neuromodulatory pharmacotherapy individualization in prolonged and chronic consciousness disorders after severe traumatic brain injury]. / K probleme individualizatsii neiromodulyatornoi farmakoterapii pri prolongirovannykh i khronicheskikh narusheniyakh soznaniya vsledstvie tyazheloi cherepno-mozgovoi travmy.

One of the most probable causes of effective therapy for post-comatose disorders of consciousness is the lack of individualization of drug prescriptions. In this observational study, we analyzed 48 courses of neuromodulatory therapy in 28 patients with prolonged and chronic disorders of consciousness following severe traumatic brain injury. Comparison of 24 effective and 24 ineffective courses demonstrated higher effectiveness of pharmacotherapy through its individualization, i.e. the choice of a drug whose neuromodulatory spectrum would correspond to neurological syndromes of neurotransmitter dysfunction. In this approach, 74% of therapy courses were effective while opposite management resulted only 34% of effective courses.

Oral ß-RA induces metabolic rewiring leading to the rescue of diet-induced obesity.

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as ß-resorcylic acid (ß-RA). Here, we show that oral supplementation with ß-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of ß-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of ß-RA. Consequently, ß-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of ß-RA supports its translational potential. Thus, ß-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study.

AIMS: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. METHODS AND RESULTS: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient's ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. CONCLUSION: In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool.

4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease.

Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.

Obesity in Prediabetic Patients: Management of Metabolic Complications and Strategies for Prevention of Overt Diabetes.

Obesity and prediabetes affect a substantial part of the general population, but are largely underdiagnosed, underestimated, and undertreated. Prediabetes differs from diabetes only in the degree of hyperglycaemia consequent to the progressive decline in residual beta-cell function. Both prediabetes and diabetes occur as a consequence of insulin resistance that starts several years before the clinical onset of overt diabetes. Macrovascular complications in patients with diabetes are mainly caused by insulin resistance. This is why in prediabetes, the overall cardiovascular risk is, by all means, similar to that in patients with diabetes. It is important, therefore, to identify prediabetes and treat patients not only to prevent or delay the onset of diabetes, but to reduce the cardiovascular risk associated with prediabetes. This review provides an overview of the pathophysiology of prediabetes in patients with obesity and the progression toward overt diabetes. We have reviewed nutritional and pharmacological approaches to the management of obesity and reduced glucose tolerance, and the treatment of the major comorbidities in these patients, including hypertension, dyslipidaemia, and Metabolic dysfunction-associated Steatotic Liver Disease (MASLD), has also been reviewed. In patients with obesity and prediabetes, the nutritional approach is similar to that adopted for patients with obesity and diabetes; treatments of dyslipidaemia and hypertension also have the same targets compared to patients with diabetes. MASLD is a critical issue in these patients; in the prediabetic state, MASLD rarely progresses into fibrosis. This highlights the importance of the early recognition of this pathological condition before patients become diabetic when the risk of fibrosis is much higher. It is necessary to raise awareness of the clinical relevance of this pathological condition in order to prompt early intervention before complications occur. The single most important therapeutic goal is weight loss, which must be early and persistent.