Treatment Modalities Research Articles

Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

BACKGROUND The number of patients undergoing solid organ transplantation has increased annually. However, infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of immunosuppressants. Carrimycin is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene (ist) from streptomyces thermotoleran. Carrimycin has good antibacterial and antiviral effects. However, no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia (SP) after solid organ transplantation. AIM To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical treatment. METHODS In March 2022, ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March 2022. When the condition was critical and difficult to control with other drugs, carrimycin was administered. These ten patients' clinical features and treatment protocols were retrospectively analyzed, and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were evaluated. RESULTS All ten patients were included in the analysis. Regarding etiological agent detection, there were three cases of fungal pneumonia, two cases of bacterial pneumonia, two cases of Pneumocystis pneumonia, and three cases of mixed infections. After treatment with carrimycin, the disease in seven patients significantly improved, the course of the disease was significantly shortened, fever was quickly controlled, chest computed tomography was significantly improved, and oxygenation was significantly improved. Finally, the patients were discharged after curing. One patient died of acute respiratory distress syndrome, and two patients discontinued treatment. CONCLUSION Carrimycin is a safe and effective treatment modality for SP following solid organ transplantation. Carrimycin may have antibacterial and antiviral effects in patients with SP following solid organ transplantation.

Combined Biologic and Surgical Interventions for Hidradenitis Suppurativa: A Systematic Review

Introduction. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent painful or suppurative lesions due to follicular occlusion. Biologics and other treatment modalities such as surgical excision are commonly used in the treatment of severe HS. However, despite the frequent use of biologics and surgical interventions in the treatment of patients with HS, an assessment of their combined effects is lacking. This systematic review aims to qualitatively analyze the efficacy of combined biologic and surgical treatment for HS. Methods. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. The databases PubMed (MEDLINE), Embase, Cochrane (CENTRAL), ClinicalTrials.gov, MedRxiv.org, and the International Clinical Trial Registry were searched from inception until May 1, 2023. Results. A total of 1,145 studies were screened, with eight studies included for data extraction. Patients receiving combined biologic and surgical treatment showed greater improvement in the severity measurements of HS, including HS Impact Assessment, HS Physician Global Assessment, HS Sartorius Score, International Hidradenitis Suppurative Severity Score, HS recurrence rate, and Dermatology Life Quality Index. However, three studies reported a prolongation of wound healing with combined biologic and surgical treatment. Conclusion. Our systematic review highlights the additive effects of using biologics and surgery together to treat HS compared to either treatment alone. However, when both treatment modalities are used simultaneously, the potential risk of prolonged wound healing must be considered. Due to the limited number and heterogeneity of the included studies, more clinical trials are needed to establish diagnostic conclusions.

Central sleep apnea in chronic heart failure with hypoxemia - treatment efficacy and hemodynamic effects of three different treatment modalities: a case report

BackgroundThe optimal treatment for central sleep apnea (CSA) depends on the underlying pathophysiology and should consider the potential for hemodynamic impairment when using positive airway pressure devices. While the long-term effects on overall cardiovascular outcome have been investigated for different device settings, the immediate hemodynamic consequences are not well understood. This is mainly due to a lack of hemodynamic monitoring during routine polysomnographic assessment. The application of most monitoring devices is either restricted by their invasiveness, e.g. in thermodilution, or cannot be used continuously like in echocardiography. Impedance cardiography (ICG), however, enables physicians to implement a continuous non-invasive monitoring of different hemodynamic parameters which can be useful in various clinical scenarios. In sleep medicine, the hemodynamic effect of initiating positive airway pressure treatment in patients with pre-existing heart failure should be of special concern.Case presentationIn this case report, we compare the efficacy of three different treatment modalities in a patient with CSA related to chronic heart failure considering the resolution of respiratory events on polysomnography (PSG). In addition, we outline the hemodynamic effects of each treatment device using ICG for non-invasive hemodynamic monitoring. Regarding the reduction of respiratory central events, long-term oxygen treatment (LTOT) and adaptive servoventilation (ASV) proved to be more efficient compared with automatic positive airway pressure (APAP). Hemodynamically, substantial differences of the cardiac performance were observed between the treatment devices. This especially applied to ASV which led to a pronounced drop in cardiac output.ConclusionOur case report indicates that treatment of CSA may induce significant changes of hemodynamic parameters which would remain undetected during routine polysomnographic assessment. We conclude that non-invasive hemodynamic monitoring may be considered when positive airway pressure treatment is initiated in patients at risk of hemodynamic impairment.

An Early Cost-Utility Model of mRNA-Based Therapies for the Treatment of Methylmalonic and Propionic Acidemia in the United Kingdom.

Novel messenger RNA (mRNA)-based therapies, currently in development, are emerging as a promising potential treatment modality for a broad range of life-threatening and life-limiting inherited liver diseases, including methylmalonic acidemia (MMA) and propionic acidemia (PA). However, owing in part to their complexity, they are likely to come at considerable financial cost to healthcare systems. The objective of this research was to synthesize available evidence on the costs and clinical consequences associated with MMA and PA for the purpose of exploratory economic evaluation of novel mRNA-based therapies using an early cost-utility model from the United Kingdom payer perspective. A Markov model was constructed to simulate the costs and outcomes associated with novel mRNA therapies, compared with a combination of dietary management and organ transplantation (standard of care) among hypothetical cohorts of new-born patients with MMA and PA. Key model drivers were identified, and a price threshold analysis was performed to estimate value-based price ranges for future mRNA therapies given willingness-to-pay thresholds for orphan diseases. mRNA therapy was associated with an additional 5.7 and 1.3 quality-adjusted life-years (QALYs) gained per patient lifetime among patients with MMA and PA, respectively. Key drivers of cost-effectiveness were relative improvement in utility among patients who receive mRNA-based therapy and transplantation, and the cost of mRNA therapy. Assuming a willingness to pay range of £100,000-£300,000 per QALY gained, the model demonstrated mRNA therapy to be cost-effective in MMA and PA at an annual treatment cost of £70,452-£94,575 and £31,313-£36,695, respectively. Despite the lack of a strong evidence base in MMA and PA, this model provides a useful tool to estimate the cost-effectiveness, and inform value-based pricing, of new mRNA-based therapies. Our analyses also identified areas for research that will have the greatest value in reducing uncertainty in future health economic evaluations of such treatments.

Pharmacologic Treatment of Chronic Constipation.

Chronic constipation is a common disease that can impair the quality of life, with a prevalence of 14% globally and 16.5% in South Korea. Straining, hard stools, the sensation of incomplete evacuation, the sensation of anorectal blockage, and manual maneuvers to facilitate defecation are the related symptoms of chronic constipation. On the other hand, medications commonly referred to as laxatives are the essentials of treatment for constipation compared to non-pharmacological treatment, such as lifestyle modifications, biofeedback, or surgery. Unfortunately, there is still an unmet need to determine if pharmacological treatment for constipation is being administered appropriately. Therefore, there are many disadvantages as to whether the indications and side effects of laxatives are adequately considered and prescribed as the primary treatment modality for constipation in a real clinical situation in Korea. Laxatives are generally recommended as the next step for patients in whom organic causes have been excluded and have not responded to initial non-pharmacologic therapies such as dietary fiber intake and exercise. Laxatives can be classified as bulk-forming laxatives, osmotic laxatives, stimulant laxatives, and other novel laxatives. On the other hand, there are distinct mechanisms underlying constipation, and appropriate administration is the most decisive. Therefore, the present investigators prepared this review to discuss appropriate pharmacological strategies for chronic constipation in Korea. Moreover, this paper also includes suggestions for appropriate pharmacological treatment options for special patient populations.

Ramaswamy Viswanathan, M.D., Dr.Med.Sc., takes office as APA president

Ramaswamy Viswanathan, M.D., Dr.Med.Sc., a longtime advocate for mental health, a medical educator and clinician‐researcher, began his term as president of the American Psychiatric Association (APA) at the conclusion of the organization's 2024 Annual Meeting in New York City. Viswanathan currently serves as interim chair of psychiatry at the State University of New York Downstate Health Sciences University, where he also directs the Consultation‐Liaison Psychiatry Service and its Fellowship Program. He is board‐certified in psychiatry, internal medicine, consultation‐liaison psychiatry, addiction psychiatry, geriatric psychiatry, and forensic psychiatry. One of his research priorities for 2024–25 is to focus on lifestyle interventions for positive mental and physical health through a holistic approach to wellness including exercise, nutrition, sleep, social connectedness, stress reduction and avoidance of risky behaviors. They will be promoted in conjunction with other treatment modalities such as psychotherapy, pharmacotherapy and neural stimulation.

P.063 Refractory pediatric CIDP converting to full recovery with rituximab

Background: Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) is a rare, acquired polyneuropathy, especially in children, affecting the peripheral nervous system. It most commonly presents in a symmetric, proximal and distal, sensorimotor fashion. Immunosuppression and immunomanipulation are treatment modalities. We present a case of a 14 year old male with severe progressive CIDP who became refractory to steroid and IVIg but responded to Rituximab. Methods: Case presentation: A 14-year-old male with a history of asymmetric quadriparesis was diagnosed with CIDP. He had an initial partial response to IVIG and prednisone but then rapidly became refractory to even weekly IVIG and prednisone. Rituximab was therefore started. Results: Within 12 weeks his strength improved from quadriplegia to walker-assisted gait. By 22 weeks he achieved independent ambulation. His JAMAR hand grip increased from 0 to 28 kg. His worst recordable median conduction velocity (CV) improved from a nadir (MRC 0/5) of 14% of normal to 52% at full recovery (MRC 5/5). Conclusions: This case highlights several important clinical points. Dramatic improvement is possible in cases of quadriplegic CIDP. Strength recovery is not linearly related to CV recovery. There appears to be a role for polytherapy.

Comparative effectiveness of different management strategies for left atrial appendage thrombus in patients on optimal NOAC therapy

Abstract Background Left atrial appendage (LAA) thrombus is the primary cause of stroke and systemic embolism in atrial fibrillation (AF). Novel oral anticoagulants (NOACs) effectively reduce the prevalence of LAA thrombosis and stroke risk. Nonetheless, there is no clear advice for patients with a NOAC-resistant thrombus, necessitating individualized decision-making without strong support of the current guidelines. Aims To analyze patients diagnosed with an LAA thrombus despite adequate NOAC therapy and to compare the efficacy of various therapeutic strategies in achieving thrombus resolution. Methods We retrospectively analyzed patients scheduled for cardioversion or catheter ablation of AF between 2014 and 2023 who were diagnosed with LAA thrombus despite being on optimal NOAC therapy. These patients underwent follow-up transesophageal echocardiography (TEE) or cardiac CT angiography. Changes in treatment modalities were divided into four groups: transition to an alternative NOAC, switch to a vitamin K antagonist (VKA), the addition of an antiplatelet agent, or the deliberate maintenance of the current treatment. Results We analyzed the data of 90 patients comprising 103 cycles of treatment. The patients were either on rivaroxaban (41%), apixaban (32%), dabigatran (15%) or on edoxaban (12%) at the time of the initial TEE. A change to a different NOAC was observed in 37% of cases, transition to a VKA in 22%, supplementation with antiplatelet therapy in 16%, while deliberate absence of treatment modification in 25% of cases. Subsequent follow-up TEE (or CT angiography in a minority of cases) was performed at a median of 68 [43 – 94] days from the baseline evaluation. Successful thrombus resolution was achieved in 72% of cases. Evaluation of therapeutic strategies revealed that any modification of treatment was three times more effective than deliberate no change in treatment; thrombus resolution was observed in 60 (81%) vs. 17 (59%) cases (OR 3.03 [1.18 - 7.75], p = 0.021). Nevertheless, no particular strategy demonstrated superior efficacy over others. Conclusions Resolution of LAA thrombus in patients already on adequate NOAC treatment may require a revision of the prior anticoagulation strategy; however, none of the commonly employed strategies appears to exhibit distinct superiority over the rest.

Probiotics in Dermatology: An Evidence-based Approach

Abstract Probiotics are viable microorganisms that confer health benefits when administered to the host in adequate amounts. Over the past decade, there has been a growing demand for the use of oral and topical probiotics in several inflammatory conditions such as atopic dermatitis, psoriasis, acne vulgaris, etc., although their role in a few areas still remains controversial. The objective of this article is to shed light on understanding the origin and implications of microbiota in the pathophysiology of these dermatological conditions and the effect of probiotic usage. We have conducted a comprehensive search of the literature across multiple databases (PubMed, EMBASE, MEDLINE, and Google Scholar) on the role of probiotics in dermatological disorders. Commensal microbes of the skin and gastrointestinal tract play an important role in both health and disease. Increased use of probiotics has asserted a good safety profile, especially in this era of antibiotic resistance. With the advent of new products in the market, the indications, mechanism of action, efficacy, and safety profile of these agents need to be validated. Further studies are required. Oral and topical probiotics may be tried as a treatment or prevention modality in cutaneous inflammatory disorders, thus facilitating decreased requirement for topical or systemic steroids and antimicrobial agents. Tempering microbiota with probiotics is a safe and well-tolerated approach in this era of antimicrobial resistance.

Demographics, clinical features and genetics of inherited arrhythmias in Oman

Abstract Background Inherited arrhythmia syndromes (IAS) are a group of rare disorders that result from genetic mutations in several genes encoding ion channels causing disruption in its structure and function and predispose affected individuals to various symptoms including sudden cardiac death (SCD). They include congenital long QT syndrome, Brugada syndrome (BrS), progressive cardiac conduction disease, short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). There have been few reports of long QT syndrome from the Arabian Gulf region but this is the first comprehensive review of multiple inherited arrhythmia syndromes in the region. Objectives Our objective are to describe the demographics of children and adults with inherited arrhythmia syndromes, report the presenting clinical features, genetic mutations and management strategies. Also, to report some unique and rare genetic findings in our population. Methods This is a descriptive retrospective study that included children and adults with inherited arrhythmia syndromes diagnosed and treated at a national heart center over 16 years, between 2006 to 2022. Data collected included patient demographics, geographical distribution, clinical features, genetic reports and management strategies. Result One hundred and six patients were included in the analysis. Sixty-six (62.3%) were males, and 68 (64.2%) were adults and 38 (35.8%) were children. Three inherited arrhythmia syndromes were found in our population that included Long QT, Brugada and catecholaminergic polymorphic ventricular tachycardia (CPVT), which accounted for 58 (54.7%), 39 (36.8%) and 9 (8.5%), respectively. Seventy-six (71.7%) of the patients were reported to be from consanguineous families. Most children, 31 (91.4%) had long QT, whereas most adults, 39(54.9%) had Brugada. The clinical features varied based on the type of arrhythmia. There were 28(26.4%) asymptomatic individuals who were diagnosed incidentally. Syncope was the most common presenting symptom in patients with Long QT, 24(41.4%) and Brugada syndrome, 20(51.3%). Palpitations, 4(44.4%) and bradycardia, 4(44.4%) were the predominant presenting features in patients with CPVT. The treatment modalities included beta blockers and antiarrhythmics, implantable cardioversion defibrillators(ICDs), pacemakers, and left sympathetic ganglionectomy(LSGs). We identified 36 individuals with pathogenic or likely pathogenic variants and 12 VOUS(variants of uncertain significance) in different genes of IAS. Conclusion This is the first comprehensive study on the inherited arrhythmia syndromes in Oman and the Arabian Peninsula. We provided insights about demographics, clinical, genetic profile and the treatment strategies of the most common IAS in the region. Tis study hat will help in early detection of the different types of arrhythmias and early intervention to prevent sudden cardiac death in patients and their relatives.

Therapeutic options for different metastatic sites arising from renal cell carcinoma: A review.

Renal cell carcinoma (RCC) stands among the top 10 malignant neoplasms with the highest fatality rates. It exhibits pronounced heterogeneity and robust metastatic behavior. Patients with RCC may present with solitary or multiple metastatic lesions at various anatomical sites, and their prognoses are contingent upon the site of metastasis. When deliberating the optimal therapeutic approach for a patient, thorough evaluation of significant risk factors such as the feasibility of complete resection, the presence of oligometastases, and the patient's functional and physical condition is imperative. Recognizing the nuanced differences in RCC metastasis to distinct organs proves advantageous in contemplating potential treatment modalities aimed at optimizing survival outcomes. Moreover, discerning the metastatic site holds promise for enhancing risk stratification in individuals with metastatic RCC. This review summarizes the recent data pertaining to the current status of different RCC metastatic sites and elucidates their role in informing clinical management strategies across diverse metastatic locales of RCC.

Clinical efficacy of titanium prepared platelet rich fibrin in periodontal regeneration: A systematic review and meta-analysis

Background Periodontal regeneration therapies frequently involve autologous platelet concentrates (APCs). They can be used in sinus lift surgeries and socket preservation, among other clinical settings. Platelet rich fibrin (PRF) membrane has been used to treat gingival recession in individuals or groups of individuals using a coronally progressed or lateral pedicle flap. In the treatment of mixed periodontic endodontic lesion/furcation defect, PRF functions as a healing and interpositional biomaterial, filling a cystic cavity. PRF is known to help the bone regeneration process. In the last few years, efforts have been made to enhance the PRFs characteristics and quality. One of them is titanium platelet rich fibrin (T-PRF). Third-generation platelet concentrate no longer contains silica, and its preparation in glass vacuum containers, that no longer creates any known concerns. The effectiveness PRF’s has been evaluated in connective tissue and bone repair. The aim of this study is to compare T-PRF to other platelet concentrates and different treatment modalities for periodontal regenerative procedures. Methods A protocol of this systematic review have been registered in prospero (CRD42022293545). The online database searched were PUBMED, COCHRANE for published articles up to November 2022 without language restrictions. Studies in trial registers, handsearching, bibliographic references of relevant articles were also checked. Data collection and analysis was done by individual authors. Independent eligibility assessments were conducted by four review authors. Then, using the standard Cochrane methodology, four review authors extracted the data and evaluated the risk of bias for individual studies. We developed “Summary of findings” tables and used GRADE to evaluate the evidence. Results Three studies were included for meta-analysis. Results of meta-analysis supported that T-PRF is effective for correction of both hard and soft tissue defects. Conclusions The overall qualitative and quantitative analysis suggest that T-PRF has superior structural properties and thicker fibrin network for ensuring predictable success periodontal regenerative procedures.

Current and Future Trends of Colorectal Cancer Treatment: Exploring Advances in Immunotherapy

Cancer of the colon and rectum (CRC) has been identified among the three most prevalent types of cancer and cancer-related deaths for both sexes. Even though significant progress in surgical and chemotherapeutic techniques has markedly improved disease-free and overall survival rates in contrast to those three decades ago, recent years have seen a stagnation in these improvements. This underscores the need for new therapies aiming to augment patient outcomes. A number of emerging strategies, such as immune checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), have exhibited promising outcomes not only in preclinical but also in clinical settings. Additionally, a thorough appreciation of the underlying biology has expanded the scope of research into potential therapeutic interventions. For instance, the pivotal role of altered telomere length in early CRC carcinogenesis, leading to chromosomal instability and telomere dysfunction, presents a promising avenue for future treatments. Thus, this review explores the advancements in CRC immunotherapy and telomere-targeted therapies, examining potential synergies and how these novel treatment modalities intersect to potentially enhance each other’s efficacy, paving the way for promising future therapeutic advancements.

Surgical treatment of peri-implantitis

As utilisation of dental implants continues to rise, so does the incidence of biological complications. When peri-implantitis has already caused extensive bone resorption, the dentist faces the dilemma of which therapy is the most appropriate to maintain the implant. Since non-surgical approaches of peri-implantitis have shown limited effectiveness, the present paper describes different surgical treatment modalities, underlining their indications and limitations. The primary goal in the management of peri-implantitis is to decontaminate the surface of the infected implant and to eliminate deep peri-implant pockets. For this purpose, access flap debridement, with or without resective procedures, has shown to be effective in a large number of cases. These surgical treatments, however, may be linked to post-operative recession of the mucosal margin. In addition to disease resolution, reconstructive approaches also seek to regenerate the bone defect and to achieve re-osseointegration.

The initiation of a migraine associated with a specific gene responsible for regulating immune function: Hypothesis

Migraine, recognized as a pervasive global health concern, is ranked the third leading cause of disability. It continues to pose significant challenges attributable to the lack of a definitive etiology and absence of universally efficacious treatment modalities. Despite extensive research and diverse treatment approaches, such as the use of CGRP antagonists, the outcomes have not consistently met expectations. Given this context, our hypothesis introduces a novel viewpoint by suggesting potential associations between migraine and deviations in immunological irregularities, specifically emphasizing the role of FOXP3. The theory posits that mutations in FOXP3 may play a central role in the migraine puzzle, implicating Treg cells and cytokines in the pathophysiology. Supporting evidence includes observed changes in T cell subsets and cytokines in patients with migraine, highlighting the intricate interplay between genetics and immune functions. To substantiate this, the author suggests employing assays targeting immune cells, autoantibodies, and specific genetic variations, and investigating B-cell activating factors and inflammatory markers during different migraine phases. This proposed connection aligns with the observed associations between autoimmune conditions and migraine, indicating shared genetic factors. Understanding the intricate relationship between genetics and immune function in migraine could offer insights into the origin of the condition and guide personalized treatment strategies, potentially marking a paradigm shift in migraine management.

Genotype, phenotype and outcomes of patients with hypertrophic cardiomyopathy referred for ablation of ventricular tachycardia

Abstract Background Sustained monomorphic ventricular tachycardia (SMVT) is the most common ventricular arrhythmia (VA) subtype in patients with hypertrophic cardiomyopathy (HCM) who have received an implantable cardioverter defibrillator (ICD). However, data on catheter ablation (CA) are limited and available series typically report results of non-genotyped patients with relatively mild hypertrophy and/or apical aneurysms. Purpose This study describes genotype, phenotype and outcome of consecutive HCM patients referred for CA ablation of refractory SMVT. Methods and results Nine out of 787 patients referred for catheter ablation of SMVT between 01/2016 – 10/2023 had a HCM phenotype, 8/9 with dominant septal hypertrophy, none with LV outflow tract obstruction, and only 1/9 with an apical aneurysm. The median maximal wall thickness was 25 mm (IQR 20,2 – 26,9 mm) and the median left ventricular ejection fraction 34 % (IQR 26-42%). Six patients had a class IV/V variant in the myosine binding protein C (MYBPC3) gene, in 3 no disease-causing variant was identified. All patients with MYBPC3 mutation presented with an electrical storm/incessant VT refractory to antiarrhythmic drugs (AAD), including amiodarone (6/6) and amiodarone + class I AAD (3/6). In an attempt to control VT, 4/6 patients with a MYBPC3 variant required ≥2 ablation including bail out strategies (transcoronary alcohol-ablation, bipolar ablation, half-saline), surgical substrate resection and intraoperative cryoablation (3/6) and radiotherapy (2/6). After a median follow-up of 25 months (IQR 2-75) after the last intervention, all patients with MYBPC3-variants had VT recurrence, 3/6 died and 1/6 underwent heart transplantation. In contrast, patients without class IV/V variants, did not require bail-out strategies; VT recurred in one (single episode) and one patient died, 24 months after CA. The time course of the disease, management and outcome for patients with and without disease causing mutation is illustrated, with the first ablation as center line (figure). Conclusions Only 1 % of patients referred for CA of SMVT to a high-volume center had a HCM phenotype. A MYBPC3 variant was identified in 67%, and, in contrast to prior reports, 89% had severe hypertrophy. VT free survival appears to be particularly poor in MYBPC3 variant carriers despite availability of all treatment modalities. In these patients, early screening for advanced heart failure management including heart transplantation is important.

Procedural heart rate variability and its effect on short-term symptoms after cardioneuromodulation procedure

Abstract Background Syncope is a miscellaneous clinical condition that affects a large portion of the population every year all over the world and responsible for a considerable amount of hospital and particularly emergency department admissions (1) The use of a right-sided approach in catheter ablation of ganglion plexi (GP) has been applied to reduce syncope episodes caused by vasovagal syncope (VVS) and decrease the overall burden of syncope (2). Purpose Our aim is to show that right-sided GP ablation which is known as cardioneuromodulation (CNM) is a new and promising way to cease recurrent syncope episodes and assess its effects on heart rate (HR), P-P intervals, ventricular depolarisation/repolarization parameters (QRS,QTc,Tpe durations, QTc/Tpe ratio), recurrence of syncope episodes, and patients symptoms such as fatigue, dizziness, etc. We also aimed to identify changes between pre and post procedural heart rates and its effects on short-term symptoms during follow-up. Methods A group of 55 patients with positive tilt table response or recurrent vasovagal syncope with pauses >2 sec in holter monitoring was enrolled this study. During the EP study, GPs determined both anatomically and by EP stimulation then autonomic denervation was performed focused by radiofrequency ablation. All patients followed-up for 12 months. Results Right-sided ablation was performed during the procedure and HR increased significantly in all patients after the procedure compared to before. Syncope episodes of the patients decreased significantly after the procedure. The patients who did not complain of syncope at the first, second and third appointment, respectively, 76.4% (n:42), 90.9% (n:50) and 92.7% (n:51). Patients had complaints at most within the first 4 months after the procedure (Table-1). At the first appointment, 4 (7.3%) patients had syncope and 9 (16,4%) patients had sinus tachycardia. Patient group with heart rate variability varying more or less than 20% during the procedure were examined, 81% of those with HR variability <20% did not have any symptoms, while 64.7% of the group with HR variability above 20% did not have any symptoms at first appointment (p:0,461) (Table.2). Tachycardia was seen in 23.5% of those with HR variability >20%, while it was determined as 9.5% in those with a HR variability <20 % Although these comparisons do not show a statistically significant difference due to the number of few patients, it is clinically significant. The same relationship was not observed between HR variability and symptoms in the second and third appointments. Conclusion Cardioneuromodulation is a remarkable treatment modality and it should be taken into consideration that more symptoms may develop in the early post-procedural period in the group who has post-procedure heart rate variability over 20%, and a cut-off should be determined for the target heart rate during the procedure.Table-1Table-2

Why clinical trials in disc regeneration strive to achieve completion: Insights from publication status and funding sources.

Chronic discogenic low back pain (LBP) poses a significant global burden, yet effective therapeutic interventions directly targeting the underlying degenerative process remain elusive. After demonstrating promising results in preclinical studies, intradiscal injection of cell-based treatments has been increasingly investigated in the clinical setting. However, most clinical trials failed to reach publication, with the few available reports showing only minor improvements. The aim of this study was to analyze the prospective clinical trials registered on ClinicalTrials.gov investigating cell therapies for LBP, with a specific emphasis on identifying critical obstacles hindering study completion, including trial design and funding sources. A systematic search of prospective clinical trials investigating cell-based treatments for chronic LBP due to intervertebral disc degeneration was performed on ClinicalTrials.gov. Extracted data encompassed study design, recruitment, experimental treatment modalities, investigated outcomes, current status, completion date, publication status, and funding sources. Fisher's exact test assessed associations between categorical variables, while a multiple logistic regression model aimed to identify factors potentially linked to the publication status of the studies. Our search identified 26 clinical trials. Among these, only 7 (26.9%) were published, and none of the other studies marked as completed reported any results on ClinicalTrials.gov. Fifty percent of included trials were funded by universities, whereas the rest was sponsored by industry (38.5%) or private institutions (11.5%). Experimental treatments primarily involved cell-based or cell-derived products of varying sources and concentrations. Products containing carriers, such as hyaluronic acid or fibrin, were more frequently funded by industry and private organizations (p = 0.0112). No significant differences emerged when comparing published and nonpublished studies based on funding, as well as between publication status and other variables. Most clinical trials exploring cell-based disc regenerative therapies for chronic LBP have never reached completion, with only a small fraction reporting preliminary data in publications.

Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma: New hopes on the horizon

In this editorial, we comment on the article by Wang et al . This manuscript explores the potential synergistic effects of combining zanubrutinib, a novel oral inhibitor of Bruton’s tyrosine kinase, with high-dose methotrexate (HD-MTX) as a therapeutic intervention for primary central nervous system lymphoma (PCNSL). The study involves a retrospective analysis of 19 PCNSL patients, highlighting clinicopathological characteristics, treatment outcomes, and genomic biomarkers. The results indicate the combination’s good tolerance and strong antitumor activity, with an 84.2% overall response rate. The authors emphasize the potential of zanubrutinib to modulate key genomic features of PCNSL, particularly mutations in myeloid differentiation primary response 88 and cluster of differentiation 79B. Furthermore, the study investigates the role of circulating tumor DNA in cerebrospinal fluid for disease surveillance and treatment response monitoring. In essence, the study provides valuable insights into the potential of combining zanubrutinib with HD-MTX as a frontline therapeutic regimen for PCNSL. The findings underscore the importance of exploring alternative treatment modalities and monitoring genomic and liquid biopsy markers to optimize patient outcomes. While the findings suggest promise, the study’s limitations should be considered, and further research is needed to establish the clinical relevance of this therapeutic approach for PCNSL.

A meta-analysis of recombinant human endostatin combined with NP regimen for treating non-small cell lung cancer.

The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of advanced non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) of NPE for advanced NSCLC in PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched using a computerized search of the database from the time of creation to May 2023. Two investigators independently extracted literature information and assessed the quality of the included literature. Meta-analysis was performed using RevMan 5.4.0 software. A total of 24 RCTs with 2114 patients with advanced NSCLC were finally included. The results of meta-analysis showed that the total effective rate in the group received NPE regimen was significantly higher than those in the group without NPE regimen (RR = 1.70, 95% CI: 1.48-1.95, P < .00001). Meanwhile, the clinical benefit rate in the group received NPE regimen was also significantly higher than those in the group without NPE regimen (RR = 1.22, 95% CI: 1.15-1.29, P < .00001). However, there was no significant difference in the incidence of adverse event rate between the 2 groups (RR = 0.98, 95% CI: 0.76-1.27, P = .88). Compared with NP (vinorelbine + cisplatin) regimens for patients with advanced NSCLC, NPE regimens improve the total effective rate and clinical benefit rate of treatment, but there can be no significant difference in adverse effects. Prospective randomized trials are needed to further validate the safety and efficacy of this treatment modality.