Clinical Evidence Research Articles

A systematic review of techniques and clinical evidence to adopt virtual reality in post-stroke upper limb rehabilitation

AbstractRecognizing the limitations of traditional therapy can be tedious and demotivating, we explore VR’s dynamic and immersive environment to potentially improve patient engagement and motivation. This approach promises accelerated recovery by integrating real-time feedback and progress monitoring. This study aims to compare various VR training techniques employed for upper limb rehabilitation in stroke survivors. We have followed the PRISMA guidelines for systematic reviews. Articles were filtered with title words such as “virtual reality rehabilitation”, “rehabilitation”, “upper limb”, “lower limb”, “interactive gaming system”, and “VR based games” were searched in databases (LILACS, PUBMED, IEEE, WoS, and Scopus). Articles published between 2005 and 2021 were analyzed. There were 820 articles found, but only the most relevant 96 papers were analyzed. Most of the studies were randomised controlled trials (RCTs) that were submitted in 2014 or beyond. The sample size ranged from 5 to 96 persons with chronic stroke, or adults and seniors. There were no samples analyzed for those under the age of 18. Nintendo Wii® and Microsoft’s Kinect were the most popular video gaming systems. In most of the publications, the intervention took place 2–3 sessions per week, for about 2–12 weeks, with each session lasting 30 to 60 min. The most assessed outcomes were body steadiness, upper extremity motor capabilities, daily tasks, and quality of life. The Fugl–Meyer Assessment was one the commonly used tool for measuring outcomes. After VR therapy, the research found that quality of life, dynamic steadiness, and upper extremity movement function improved. To achieve dynamic equilibrium, VR proved more beneficial than traditional treatments. The most important outcomes, the researchers focused, were day-to-day activity and physical movements of the patients. Some studies investigated the early consequences of VR on daily activities and social involvement.

Microglial and Macrophage Plasticity and Regional Cerebral Blood Flow in the Prenatal Brain and Gut Under Vagus Nerve Stimulation.

An intricate relationship exists between the vagus nerve and systemic immune cell regulation, specifically during fetal development. Little is known about the connection between the vagus nerve and the brain's regional circulatory control. In this chapter, we present a methodology for studying the impact of vagus nerve signaling on these connections in the developing fetus using the sheep model for human fetal physiology. First, we present the protocol to study the connection between the vagus nerve physiology and the regional cerebral blood flow (rCBF). Next, we detail the protocol for measuring how vagal signaling alters microglial cell plasticity in gut and brain. In previous work, our team showed that vagotomy results in amplified redistribution of rCBF toward subcortical structures in the fetal brain. Conversely, efferent VNS reduces rCBF to cortical structures while afferent VNS diminishes the rise of rCBF to subcortical structures (independent of cortical rCBF) when compared to controls in the fetal brain. Additionally, our team showed that Iba-1 expression, a marker for microglial cellular signaling activation, rises in a dose-dependent relationship with systemic inflammatory activation in the setting of vagotomy. The findings support existing preclinical and clinical evidence in adult human physiology that vagotomy is neuroprotective for neurodegenerative diseases such as Parkinson's likely via a glial cell-mediated mechanism. Vagus nerve stimulation (VNS) has also been shown to alter rCBF patterns in adults with treatment-resistant depression, underscoring the importance of further investigation of the relationship between the vagus nerve and rCBF as early as in utero. Together, the body of evidence emphasizes that the vagal pathway is an important player in the programming of microglial cell phenotypes within the developing brain. Further study is needed to better understand the significance of these relationships for the development and treatment of early susceptibility to neuroinflammatory and neurodegenerative disorders in later life. Therefore, we present a methodology for assessing rCBF and morphometric features of microglial and macrophage cell activation to allow future teams to expand on the existing body of work and further examine these relationships at a cellular and systems' levels.

Advanced Deep-Plane Rhytidectomy: Advantages for Neck Treatment and Volumization of the Midface.

The aged neck is the most common motivator for patients seeking facial rejuvenation. Unlike the deflated midface, surgical treatment is still the gold standard for optimal outcomes. It is our view that the majority etiology of both the aged neck and deflated midface is gravity's effects on the superficial soft tissue envelope, leading to soft tissue redundancy. It is also our view that the deep-plane rhytidectomy is supported by anatomy, embryology, and clinical evidence as the best methodology to treat soft tissue redundancy without producing the aesthetic and longevity issues associated with superficial musculoaponeurotic system techniques. As one of the early pioneers in deep-plane rhytidectomy, the lead author will define contemporary advances in deep-plane technique such as dissection entry point, flap design, and flap fixation concepts that allow aggressive approach to treating both the aged neck and deflated midface.

Factors Influencing the Success of Non Vascularized Iliac Bone Graft for Mandibular Reconstruction: A Retrospective Study of 26 Cases

Objective: This study aimed to identify the prognostic factors influencing the success of nonvascularized iliac bone grafts for mandibular reconstruction. Methods: This was a retrospective cohort study conducted at a single center, involving 26 patients who underwent segmental mandibulectomy followed by nonvascularized iliac bone grafts between 2012 and 2022 at the Oral and Maxillofacial Surgery Unit, Buddhachinaraj Phitsanulok Hospital. Data were collected by reviewing electronic medical records and radiographic images. Patients who had received vascularized bone grafts or had a history of head and neck irradiation therapy were excluded from the study. The patients were classified into two groups: successful and failed. Success was defined as clinical and radiographic evidence of bone continuity, a graft resorption rate not exceeding 30% of the initial height, and no evidence of chronic infection for at least 6 months. Results: Successful bone grafting was achieved in 19 patients (73.1%). Multivariable risk difference regression analysis identified that the factors influencing graft incorporation were jaw immobilization using reconstruction plates with maxillomandibular fixation for at least 21 days (RD 63.0; 95% CI 33.1, 93.0; p<0.001) and long segmental block graft design (51.3%; 95% CI 16.9, 85.7; p<0.003). A clinically significant factor, although statistically insignificant, was the duration of plate stabilization, which should ideally range from 172 to 232 days prior to plate removal. The sample size constituted a limitation of this study. Conclusions: Nonvascularized bone grafting remains a viable option for reconstructing mandibular segmental defects. The factors influencing graft stability can help improve clinical outcomes.

Locally advanced/metastatic non-small-cell lung cancer in Lebanon: focus on ALK tyrosine kinase inhibitors.

Treatment of non-small-cell lung cancers (NSCLC) has evolved over the last decade. According to studies, the use of targeted therapies has significantly increased the life expectancy of patients. Moreover, ALK-tyrosine kinase inhibitors (ALK-TKIs) have improved clinical outcomes. In Lebanon, translating recommendations into clinical practice remains challenging. A Lebanese expert panel of oncologists was convened to describe the management paradigm and the clinical evidence supporting the optimal use of next-generation TKIs in patients with ALK-rearranged NSCLC and to provide an expert overview of local challenges and recommendations for optimizing the management of advanced NSCLC in Lebanese patients. The experts agreed that these recommendations should be part of a healthcare strategy to be implemented at the national level.

Treatment discontinuation in adults with atypical hemolytic uremic syndrome (aHUS): a qualitative study of international experts' perspectives with associated cost-consequence analysis.

Atypical hemolytic uremic syndrome (aHUS) is a rare, life-threatening thrombotic microangiopathy (TMA) related to congenital mutations impeding control of the alternative pathway of complement. Following approval of the complement C5 inhibitor eculizumab by the European Medicines Agency and the US Food and Drug Administration, initial guidelines suggested lifelong therapy. Yet, growing evidence indicates that discontinuation of eculizumab, or its long-acting form ravulizumab, is possible for many patients. This mixed-methods study sought to explore international experts' perspectives and experiences related to treatment duration in adult patients with aHUS, while also estimating the financial and potential health consequences of early discontinuation. Between January and December 2023, we conducted 10 qualitative interviews with experts in the treatment of aHUS, based upon which we constructed a quantitative decision tree, designed to estimate time on treatment and treatment- and disease-related adverse events. Thematic analysis of the interview data identified four main themes: (1) Concerns and prior experience; (2) High-risk vs. low-risk groups; (3) Patient preference and adherence; and (4) Funding for monitoring and re-treatment. Although most interviewees were in favour of considering treatment discontinuation for many patients (citing the high cost, burden, and potential side effects of lifelong treatment as key reasons), a prior negative experience of discontinuation seemed to make others more reluctant to stop. Deciding which patients required lifelong treatment and which not involved consideration of a wide range of factors, including patient- and system-related factors. Cost-consequence analysis demonstrated the financial savings associated with early treatment discontinuation at the expense of increased risk of recurrent TMA events. Close monitoring for these events had the potential to minimise any long-term injury, primarily renal, with an estimated one event per 100 patient years. For patients at high risk of TMA and with poor adherence to monitoring, rates of renal injury rose to three events per 100 patient years. aHUS treatment protocols are changing globally in response to new clinical evidence. Against this backdrop, our mixed-methods study provides compelling evidence on the complexity of factors influencing treatment discontinuation decisions in aHUS, as well as the financial and health consequences of early discontinuation.

Health Literacy and Attitudes Towards Childhood Epilepsy

ABSTRACT Purpose The purpose of this study was to investigate the public attitudes toward childhood epilepsy and the effects of health literacy and some sociodemographic variables on these attitudes. Design It is a descriptive and cross-sectional study. Methods The study was carried out with 311 individuals. Data were collected through face-to-face interviews with individuals using the Sociodemographic Characteristics Information Form, The Childhood Epilepsy Attitude Scale (CEAS), and the Health Literacy Scale (HLS). The data were evaluated using percentage and number, student t-test, One Way Anova, and hierarchical linear regression analysis. Findings The mean CEAS score of the participants was 43.61 ± 7.86 and the mean HLS score was 100.19 ± 17.90. According to the CEAS subscale/total score averages, no statistically significant difference was found between the variables of gender, family type, having children, family history of epilepsy, and history of epilepsy in one’s close circle (p > .05). Conclusions It was concluded that participants’ attitudes toward childhood epilepsy were positive, and that this attitude was affected by variables such as educational status, witnessing individuals having epileptic seizures, and health literacy. Clinical Evidence It is recommended that health professionals organize training programs to increase public understanding of childhood epilepsy and improve individual attitudes toward the condition. Community health nurses can play an important role in raising awareness about childhood epilepsy. Community healthcare centers may be advised to include the issue of childhood epilepsy in their awareness programs.

Acupuncture for patients with Alzheimer's disease: An evidence map of randomized controlled trials, systematic reviews, and meta-analysis.

Background: Acupuncture is an effective complementary treatment for Alzheimer's disease (AD). This review aims to summarize the available evidence provided by randomized controlled trials (RCTs) and systematic reviews (SRs) or meta-analyses (MAs) on the effect of acupuncture on AD. Objective: To systematically summarize and combine clinical research evidence on AD distribution. Methods: We conducted a comprehensive search of various databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data, Chinese BioMedical Literature Database (CBM) and Chonqing VIP (CQVIP), from their inception to September 2023. Relevant literature about acupuncture for AD was included, and the characteristics of the evidence map were presented through charts and textual analyses. Results: In total, 117 RCTs and 17 SRs or MAs were included. The results were divided into three categories: basic characteristics of the included literature, clinical characteristics and quality assessment of the included RCTs, and clinical characteristics and quality assessment of the included SRs and MAs. Conclusions: Acupuncture as a therapeutic measure for AD has some advantages in improving cognition and quality of life; thus, it is imperative to conduct multi-center, large-scale RCTs to enhance the evidence supporting the use of acupuncture in AD. This is the first evidence map exploring acupuncture treatment for AD, providing insights into the current clinical research landscape on acupuncture treatment for AD. Furthermore, the findings of this study highlight research gaps in this field and serve as a valuable reference for guiding the planning and selection of topics for future research.

Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy.

Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.

Safety and Efficacy of opioid-sparing Anesthesia Compared with Traditional opioid-anesthesia

Objectives: The rationale of adoption opioid sparing anesthesia (OSA) is to achieve perioperative analgesia with a minimal amount of opioid combined to non-opioid adjuvants during and after surgery, namely multimodal anesthesia. The OSA approach was originally developed to overcome the known complications of opioid-based anesthesia (OA) and the present scoping review (ScR) aims at providing the clinical evidence of safety and efficacy of OSA with respect to OA. Methods: This ScR is mainly focused on studies presenting evidence on the safety and efficacy of OSA versus OA. PubMed, EMBASE databases were utilized to find relevant studies. Search strategy included the following keywords: “opioid sparing anesthesia complications, opioid sparing anesthesia efficacy, opioid sparing anesthesia safety”. The findings from the 25 included studies were categorized into the following subsections: article characteristics, goals of the studies, OSA protocols, and surgical settings analyzed. Results: In the 25 reviewed studies, evidence related to the impact of OSA versus OA was considered. Intraoperative safety and efficacy endpoints include hemodynamic stability and anesthetic/analgesic requirements. Postoperative endpoints include early cognitive dysfunction, opioid-induced bowel disorder, the physical status of mothers and newborns after labor and emergency cesarean, systemic immune and inflammation modifications, postoperative recovery, in-hospital and long-term opioid requirement, early postoperative pain, chronic postsurgical pain. The studies reported a lower intraoperative mean arterial pressure and heart rate fluctuations when α2 agonists are adopted, while no differences were recorded for other complication rates. Analysis of OSA approaches for the postoperative conditions includes α2 agonists, NMDA receptor blocking agents, gabapentinoids, nefopam hydrocloride and locoregional anesthesia techniques with a positive impact on most of the endpoints considered. Discussion: The clinical implementation of OSA encompasses the perioperative use of non-opioid drugs and locoregional anesthesia techniques. The reviewed studies reported OSA as a feasible approach to reduce opioid-related complications with no impact on patient’s safety.

Distribution and Morphologic Characteristics of Choroidal Vortex Veins in Pachychoroid Disease.

This study aimed to elucidate the distribution and morphological features of choroidal vortex veins in pachychoroid disease (PCD). Retrospective observational study. Patients with PCD included from January 2022 to June 2023. We conducted a retrospective cross-sectional analysis using wide-field indocyanine green angiography (WF-ICGA) to assess choroidal vortex veins in PCD patients, categorizing them based on location (equatorial/posterior) and morphology (absent, incomplete, complete, complete with ampulla). The incidence of different location and morphology of vortex veins in PCD. A total of 190 eyes from 99 PCD patients were examined. Notably, only 8.9% (17/190) of eyes had posterior vortex veins. We identified 1620 vortex veins, predominantly equatorial (99%, 1603/1620). Morphologically, the most common type was incomplete (61.9%), followed by complete (19.5%), absent (11.1%), and complete with ampulla (7.5%). The distribution of these veins varied, with the inferotemporal quadrant showing the highest prevalence at 26.9%, followed by the superonasal (26.1%), superotemporal (24.3%), and inferonasal (22.7%) quadrants. The median number of vortex veins per eye was 8, with a range from 5 to 15. This study highlights that posterior vortex veins are less frequent in PCD eyes, with incomplete veins being the most prevalent. These findings provide important clinical evidence for understanding the distribution and morphologic characteristics of choroidal vortex veins in PCD, contributing to our knowledge of the pathophysiological mechanisms underlying this condition.

Dance for Wellness: Indigenous adolescents’ Perspectives on Mental Health, Wellness, and Dance

ABSTRACT Purpose Indigenous adolescents living on reservations in Canada experience mental health disparities, and there is an urgent need to address this as mental illness and suicide increase. Therefore, a dance program was initiated to attempt to improve mental health and wellness for Indigenous adolescents The reaearch purpose was to gain insight into theexperiences of mental health and wellness in Indigenous adolescents and identify if and how a four-week dance program affected their mental health and wellness. Design A trauma-informed, qualitative, single-case study design was used. Method Semi-structured interviews and symbol-based data were used to interview eight adolescents aged 11 – 16 years living in a Denesuliné community from February to June 2022. Findings Three multidimensional themes emerged: It Helped My Mental Health and Everything (Dance Helps Me Escape, Dance Makes Me Feel Good, and Dance Is Just Really Fun); A Little Bubble Around Me When I Dance (I Can Be More Confident and I Can Be Myself), and We Won’t Judge You Here (Creation of Friendship, He Said I Was Really Good, and Improved School Attendance). Conclusions The dance program impacted the participants’ mental health and wellness by providing positive activities to engage the adolescents. Clinical Evidence Community health nurses (CHNs) assist in promoting health and wellness in Indigenous adolescents living on reservation and can use these findings to advocate for funding for the development of dance-based mental health and wellness programs.

Expert consensus for pertussis in children: new concepts in diagnosis and treatment.

Pertussis resurgence has been reported worldwide in the past two decades. Pertussis is still endemic and difficult to control though with universal vaccination in children. The resurgence may be related to multiple variables, such as increased disease awareness and laboratory tests, waning of immunity following vaccination, and/or genetic mutations of Bordetella pertussis. For better pertussis prevention, diagnosis, and management, we called up an expert panel to develop this expert consensus to provide new concepts in diagnosis and treatment for clinical practice. The expert groups collected clinical evidence, summarized their clinical experiences, evaluated preliminary recommendations or guidelines, and then organized open-ended discussions to form the recommendations. This consensus was developed by reviewing the literature and studies in databases, including PubMed, Cochrane, EMBASE, the China Biomedical Database, and the Chinese Journal Full-text Database up to May 2024. The search terms included "pertussis" or "whooping cough", "children", "diagnosis", and "treatment". The burden of pertussis has also changed from infants to schoolchildren and adults, and these age groups have consequently become the main source of infection for vulnerable population including infants and newborns. In China, a high prevalence of erythromycin-resistant Bordetella pertussis (ERBP) has been reported in the past decade. ERBP may lead to failed clinical empirical treatment with macrolides, which poses a great challenge for pertussis management and control. For better management of pertussis, a flow diagram for diagnosis and treatment of pertussis was presented in this consensus. This consensus also described the diagnostic criteria for pertussis, high-risk cases, and severe pertussis. Macrolides can still be used to treat confirmed erythromycin-sensitive B. pertussis (ESBP) infections, whereas oral trimethoprim-sulfamethoxazole therapy is the initial treatment option for children older than twomonths. For infants younger than twomonths, severe patients, or those exhibiting a high degree of sulfonamide allergy, intravenous administration of piperacillin or cefoperazone-sulbactam is advised. This expert consensus provides a comprehensive guidance and a reference for the diagnosis and treatment of pertussis in children.

Clinical efficacy of Chinese herbal medicine formula for Graves' hyperthyroidism: A multicentre, randomized, double-blind, placebo-controlled clinical trial.

According to the theory of traditional Chinese medicine,Graves' disease (GD) is called 'Ying Bing', which is a kind of goiter. Haizao Yuhu decoction, originated from the medical book of the Ming Dynasty 'Waikezhengzong', is a classic Chinese herbal formula for the treatment of 'Ying Bing' for more than 400 years. Pingkang granules, modified from the Chinese herbal formula Haizao Yuhu decoction specialized in GD, has shown effectiveness in several single-centre studies. However, high-quality clinical evidence for the management of GD using Pingkang granules remains insufficient. To obtain high-quality medical evidence for the treatment of GD with Pingkang granules through randomized controlled clinical trial. A multicentre, randomized, double-blinded, placebo-controlled clinical trial was designed. A total of 186 patients with Graves' hyperthyroidism from five medical centers were randomly assigned to receive methimazole [MMI] and Pingkang granules placebo (group A), MMI and Pingkang granules (group B), or MMI placebo and Pingkang granules (group C) in a 1:1:1 ratio for 12 weeks. The primary clinical outcomes were serum free triiodothyronine (FT3) and free thyroxine (FT4) levels from baseline until the end of the research. Secondary clinical outcomes included serum thyrotrophin receptor antibody (TRAb) levels at 4- and 12-weeks post-intervention, thyroid volume, peak systolic velocity of the superior thyroid artery (STA-PSV), 39-item version of Thyroid-Related Patient-Reported Outcome (ThyPRO39) scores, and safety assessment included blood routine, liver and kidney function tests from baseline to the endpoint. 150 patients were included in the full analysis set for efficacy analysis, including 48, 50, and 52 in groups A, B, and C, respectively. At the endpoint, three regimens significantly reduced serum FT3 levels (group A, p=0.0027; group B, p<0.0001; group C, p=0.0028) and FT4 levels (group A, p<0.0001; group B, p<0.0001; group C, p<0.0001), and the combination of MMI and Pingkang granules markedly reduced serum TRAb levels (p=0.0014). The thyroid volume in group A was significantly larger than that at baseline at week 12 (p=0.0370), and there were no statistically significant differences in the thyroid volume among groups at week 4 (p=0.7485) and 12 (p=0.1333). STA-PSV values in group B were significantly higher than those in group A at week 4 (p=0.0409). The STA-PSV levels in groups A (p<0.0001) and C (p=0.0025) were significantly lower than those at baseline at week 4, and STA-PSV levels in all groups were significantly lower than those at baseline at week 12 (group A, p=0.0095; group B, p=0.0138; group C, p=0.0423). Pingkang granule monotherapy significantly ameliorated symptoms related to hyperthyroidism (p<0.0001), eye (p=0.0490), tiredness (p<0.0001), cognition (p<0.0001), depression (p=0.0478), and susceptibility (p=0.0052). No severe adverse events were reported in either group or three regimens showed similar safety. Pingkang granules significantly reduced serum FT3, FT4 and STA-PSV levels, improved ThyPRO39 scores, and lowered serum TRAb levels when combined with MMI in patients with Grave's hyperthyroidism.

RECENT DEVELOPMENTS IN ENDOVASCULAR THERAPY FOR CHRONIC SUBDURAL HEMATOMAS USING LIQUID EMBOLIC AGENTS

Chronic subdural hematomas (cSDH) remain a significant challenge in neurosurgery, particularly among the elderly. Recent advancements in endovascular therapy, specifically the use of non-adhesive embolic agents, have shown promise in improving outcomes for these patients. This presentation will delve into the latest developments and clinical evidence surrounding this innovative approach. The discussion will include findings from recent randomized trials that have evaluated the efficacy and safety of embolisation with non-adhesive agents, both as a standalone treatment and in conjunction with traditional surgical methods. Technical outcomes from these studies will be analyzed, highlighting key differences in patient recovery, complication rates, and long-term results between the combined and isolated approaches. One of the focal points of the presentation will be the technical nuances of performing embolisation, emphasizing the procedural intricacies and the choice of embolic materials. Comparative data will be presented to illustrate the benefits of non-adhesive agents over other embolisation methods, particularly in terms of reducing re-bleeding rates and minimizing invasive interventions. Additionally, we will explore future implications of widespread adoption of this technique, including its potential to alter standard care practices and improve patient prognoses. Projections will be made regarding the impact on healthcare resources, patient quality of life, and overall survival rates. The presentation aims to provide a comprehensive overview of the current state and future potential of endovascular therapy for cSDH, offering valuable insights for neurosurgeons and interventional radiologists seeking to enhance their therapeutic arsenal.

Treatment of Acanthamoeba keratitis with high dose PHMB (0.08%) monotherapy in clinical practice: A case series.

Acanthamoeba keratitis (AK) is a rare sight-threatening infectious disease with no approved pharmacological treatments. Topical polihexanide 0.8 mg/ml (PHMB 0.08%) completed a pivotal clinical trial showing a medical cure rate of 84.9%. The purpose of this study is to evaluate the efficacy and safety of PHMB 0.08%, given as monotherapy, in clinical practice. consecutive cases of AK were included. Diagnosis was confirmed by in vivo confocal microscopy or PCR. Patients were treated with PHMB 0.08% as part of a name-based compassionate use program. Treatment delivery frequency and termination were as advised in the pivotal clinical trial. Medical cure was defined as clinical evidence of healed epithelium and absence of corneal inflammation lasting 3 months after discontinuing all treatments. twelve eyes of 11 contact lens wearers with AK of variable severity were evaluated. Eleven of 12 (91.7%) eyes achieved a medical cure with no surgery. One eye had a corneal perforation and required emergency therapeutic keratoplasty. The median time of treatment with PHMB 0.08% was 100 days (range 35-222). Seven eyes (58.3%) reached a final visual acuity of 20/50 Snellen or better. Two subject reported worsening of conjunctival hyperaemia during the intensive phase of the treatment. No other adverse drug reactions were observed. topical treatment with PHMB 0.08% monotherapy successfully cured AK in 11 of 12 eyes when used in real-world clinical practice, thereby confirming that results observed in the clinical trial could be obtained in this setting.

The Impact of Sira Vedha (Phlebotomy) at the Right Elbow Joint in the Treatment of Non-Alcoholic Fatty Liver Disease - A Research Report

ABSTRACT Non-alcoholic fatty liver disease (NAFLD) affects 9%–53% of the Indian population. No Indian studies have examined Sira Vedha (phlebotomy) for NAFLD, although it has been studied for other conditions. Sushruta recommended Sira Vedha at the right elbow joint for liver diseases, but clinical evidence for its efficacy in NAFLD is lacking. This clinical trial aimed to generate evidence for Sira Vedha in NAFLD patients. One hundred eleven patients with Grade I/II NAFLD were randomly assigned to either a control group (diet and exercise) or an intervention group (Sira Vedha, diet, and exercise). Blood samples were collected for lipid profile and liver function tests before and after treatment. Results showed significant improvements in SGOT, SGPT, cholesterol, HDL, and triglyceride levels in the intervention group compared to the control group, supporting the efficacy of Sira Vedha in NAFLD treatment. This study highlights the need for clinical evidence to confirm traditional Ayurvedic practices.

Navigating SARS-CoV-2-related immunopathology in Crohn's disease: from molecular mechanisms to therapeutic challenges.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only posed major health and economic burdens to international societies but also threatens patients with comorbidities and underlying autoimmune disorders, including Crohn's disease (CD) patients. As the vaccinated population is gradually relieved from the stress of the latest omicron variant of SARS-CoV-2 due to competent immune responses, the anxiety of CD patients, especially those on immunosuppressive treatment, has not subsided. Whether the use of immunosuppressants for remission of CD outweighs the potential risk of severe coronavirus disease 2019 (COVID-19) has long been discussed. Thus, for the best benefit of CD patients, our primary goal in this study was to navigate the clinical management of CD during the COVID pandemic. Herein, we summarized COVID-19 outcomes of CD patients treated with immunosuppressive agents from multiple cohort studies and also investigated possible mechanisms of how SARS-CoV-2 impacts the host immunity with special consideration of CD patients. We first looked into the SARS-CoV-2-related immunopathology, including lymphocytopenia, T-cell exhaustion, cytokine storms, and their possible molecular interactions, and then focused on mechanistic actions of gastrointestinal systems, including interruption of tryptophan absorption, development of dysbiosis, and consequent local and systemic inflammation. Given challenges in managing CD, we summarized up-to-date clinical and molecular evidence to help physicians adjust therapeutic strategies to achieve the best clinical outcomes for CD patients.

PCSK9 in metabolism and diseases.

PCSK9 is a serine protease that regulates plasma levels of low-density lipoprotein (LDL) and cholesterol by mediating the endolysosomal degradation of LDL receptor (LDLR) in the liver. When PCSK9 functions unchecked, it leads to increased degradation of LDLR, resulting in elevated circulatory levels of LDL and cholesterol. This dysregulation contributes to lipid and cholesterol metabolism abnormalities, foam cell formation, and the development of various diseases, including cardiovascular disease (CVD), viral infections, cancer, and sepsis. Emerging clinical and experimental evidence highlights an imperative role for PCSK9 in metabolic anomalies such as hypercholesterolemia and hyperlipidemia, as well as inflammation, and disturbances in mitochondrial homeostasis. Moreover, metabolic hormones - including insulin, glucagon, adipokines, natriuretic peptides, and sex steroids - regulate the expression and circulatory levels of PCSK9, thus influencing cardiovascular and metabolic functions. In this comprehensive review, we aim to elucidate the regulatory role of PCSK9 in lipid and cholesterol metabolism, pathophysiology of diseases such as CVD, infections, cancer, and sepsis, as well as its pharmaceutical and non-pharmaceutical targeting for therapeutic management of these conditions.

Abstract B018: Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer

Abstract Purpose: Squamous cell carcinoma of the anus (SCCA) is primarily driven by human papillomavirus (HPV) infection. Up to 30% of patients experience recurrence, necessitating improved surveillance strategies. Liquid biopsies have shown promise as a tool in oncology. This study investigates the clinical performance of circulating tumor tissue modified viral (TTMV)- HPV DNA in the post-treatment surveillance of SCCA. Patients and methods: This central IRB-approved retrospective cohort study included 117 patients diagnosed with HPV-driven SCCA from seven U.S. centers who had ≥1 TTMV-HPV DNA tests (NavDx®, Naveris, Inc., Waltham, MA) performed between March 2020 and June 2024. TTMV-HPV DNA for HPV subtypes 16, 18, 31, 33, and 35 were analyzed using droplet digital PCR. The diagnostic accuracy of TTMV-HPV DNA was evaluated by comparing test results with clinical evidence of SCCA recurrence determined through anoscopy, radiology, and/or tissue biopsy. Recurrence is defined as either a positive biopsy or subsequent salvage therapy. Results: Patients were primarily female (73%) with a median age 63 years. Median follow-up after initial treatment was 19 months. Forty-seven patients (40%) had pretreatment TTMV-HPV DNA testing, with a baseline detectability of 85.1% (40/47, 95% CI: 74.9–95.3). Of these, 24 were re-tested within 3 months post-treatment and 18 had undetectable TTMV-HPV DNA (75%). Those patients whose scores became undetectable had significantly longer recurrence-free survival than those whose scores remained detectable (log-rank test, p=0.01). One hundred and four patients (89%) underwent post-treatment testing, of which 91 provided relevant data for the analysis. Of these 91 patients, 27 (29.7%) experienced recurrence. Post-treatment testing demonstrated a per- patient sensitivity of 85.7% (24/28, 95% CI: 72.8-98.7). Of four patients with a false negative test, only one had biopsy-confirmed recurrence, whereas the remaining recurrences were not biopsied prior to starting salvage treatment. The positive predictive value of a single positive test was 97.6% (40/41; 95% CI: 92.8–100.0). One patient remains in active follow-up. Of the true positive post-treatment tests, 58% (14/24) predicted recurrence before clinical detection, with a median lead time of 59 days (range: 10–536). There were 141 negative post-treatment tests across 66 patients. This yielded a per-test specificity and negative predictive value of 99.3% (136/137, 95% CI: 97.8-100.0) and 97.2% (136/140, 95% CI: 94.9-99.9), respectively. Indeterminate TTMV-HPV DNA tests were rare (5/268,1.9%). However, clinically indeterminate findings (CIFs) were common, with 141 post-treatment CIFs identified across 52/117 patients (44.4%). TTMV-HPV DNA testing was able to correctly predict recurrence status in 94.3% of CIF cases. Conclusion: TTMV-HPV DNA testing is a sensitive and specific surveillance method for detecting early recurrence of HPV-driven SCCA. Citation Format: Shane Lloyd, Rafi Kabarriti, James Jabalee, Tyler Slater, Corbin Jacobs, Sean Inocencio, Michael Rutenberg, Chance Matthiesen, Kasha Neff, Gene-Fu F Liu, Tiffany M Juarez, Catherine DV Fitz, Stanley Liauw. Plasma-based circulating tumor tissue modified viral (TTMV)-HPV DNA for detection of recurrent HPV-driven anal cancer [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr B018.