Relief Of Symptoms Research Articles

Evaluation of the effect of dextrose prolotherapy versus deep dry needling therapy for the treatment of temporomandibular joint anterior disc displacement with reduction: (a randomized controlled trial).

to compare the combined effect of Prolotherapy and Deep Dry Needling (DDN) versus DDN effect on relieving the symptoms of Temporomandibular joint (TMJ) anterior disc displacement. The clinical trial randomly allocated forty patients. The (control group) patients received four intraarticular and masseteric DDN sessions, while the (study group) patients were subjected to the exact technique followed by Prolosolution injection. The baseline preoperative measurements included Maximal interincisal opening (MIO), auscultation of the presence of clicking, and Visual Analogue Scale (VAS), which were repeated for postoperative measurements after one, two, five, and eight months. By the end of the study, all patients expressed apparent improvement in pain MIO and clicking. The inter- and intragroup comparison revealed that the pain score values of the control group after five and eight months were significantly higher than those of the study group. The study group demonstrated more significant MIO calibration than the control group, with insignificant differences between both groups regarding the presence of clicking at any time interval. The associations between clicking and VAS values, between clicking and MIO, and between VAS values and increased MIO were positive in the test group and negative in the control group. Dextrose Prolotherapy and DDN were beneficial. However, Prolotherapy demonstrated more significant, sustained, and correlated long-term alleviation of symptoms and increased MIO. The study assesses the sole effect of dextrose prolotherapy on relieving the signs of TMJ anterior disc displacement apart from the impact of the penetrating needle. The study was registered on www. gov (#: NCT05821985) by Ahmed Nagi Alghandour.

Arthroscopic Repair of Extruded Meniscus Tears: Impact on Symptom Relief and Functional Improvement - A 2-Year Follow-Up Study.

BACKGROUND This retrospective study from a single center in Turkey aimed to evaluate 2-year outcomes of 21 patients undergoing knee arthroscopic repair of extruded meniscus tears without root tear. MATERIAL AND METHODS The retrospective study comprised 21 individuals who underwent arthroscopic extruded meniscus repair and were followed up for at least 2 years. The study analyzed the meniscus extrusion amounts in preoperative and postoperative MRI scans, the Kellgren-Lawrence stages in knee radiographs, and the Lsyhom and The International Knee Documentation Committee (IKDC) scores of the included patients. RESULTS In this study, the repair operation extrusion levels were 3.30 mm from 4.01 mm preoperatively (P<0.001). After the repair, there was a significant increase in the Lsyhom and IKDC scores (P<0.001). According to the Kellgren-Lawrence scale, 12 patients were evaluated as stage 0, 6 patients as stage 1, and 3 patients as stage 2. According to the radiographs taken at the last follow-up, 2 patients progressed from stage 0 to stage 1, 2 patients progressed from stage 1 to stage 2, and 1 patient progressed from stage 2 to stage 3. CONCLUSIONS Arthroscopic treatment of extruded meniscus tears can enhance functional status and increase patients' functional status. Nevertheless, the absence of successful centralization extruded meniscus tears. This study discovered that radiological extrusion did not diminish beyond the critical threshold of 3 mm, which is associated with the development of osteoarthritis. This highlights the necessity of taking these elements into account when devising a treatment plan.

Mechanisms and treatment of pulmonary arterial hypertension.

Substantial progress has been made in the management of pulmonary arterial hypertension (PAH) in the past 25 years, but the disease remains life-limiting. Established therapies for PAH are mostly limited to symptomatic relief by correcting the imbalance of vasoactive factors. The tyrosine kinase inhibitor imatinib, the first predominantly non-vasodilatory drug to be tested in patients with PAH, improved exercise capacity and pulmonary haemodynamics compared with placebo but at the expense of adverse events such as subdural haematoma. Given that administration by inhalation might reduce the risk of systemic adverse effects, inhaled formulations of tyrosine kinase inhibitors are currently in clinical development. Other novel therapeutic approaches for PAH include suppression of activin receptor type IIA signalling with sotatercept, which has shown substantial efficacy in clinical trials and was approved for use in the USA in 2024, but the long-term safety of the drug remains unclear. Future advances in the management of PAH will focus on right ventricular function and involve deep phenotyping and the development of a personalized medicine approach. In this Review, we summarize the mechanisms underlying PAH, provide an overview of available PAH therapies and their limitations, describe the development of newer, predominantly non-vasodilatory drugs that are currently being tested in phase II or III clinical trials, and discuss future directions for PAH research.

Transorbital puncture for the treatment of cavernous sinus dural arteriovenous fistulas.

Endovascular embolization of carotid-cavernous sinus dural arteriovenous fistulas (CCFs) is most commonly performed via a transfemoral-transvenous approach. Surgical cut-down of the superior ophthalmic vein is an alternative, well-described route. When these prove inaccessible, a transorbital approach can be used to reach the fistula. We describe the recent experience- including indications, surgical technique, radiological findings and post-operative outcomes- in Melbourne of a series of patients in whom a percutaneous, transorbital direct puncture of the cavernous sinus enabled successful embolization of dural arteriovenous fistulas. Each of three patients achieved successful embolization of their CCFs via a transorbital puncture. Post-operatively, all patients experienced symptomatic relief with complete resolution of clinical signs secondary to their CCFs. When angioarchitecture does not allow endovascular access, transorbital puncture of carotid-cavernous sinus dural arteriovenous fistulas can be a safe and effective technique. This report supports its success and low complication rate.

Tibial Tubercle Osteotomy: Indications, Outcomes, and Complications.

The tibial tubercle osteotomy (TTO) is a versatile surgical technique used to treat a range of patellofemoral disorders, including patellar instability, painful malalignment, focal chondral defects, and patellar maltracking that have failed conservative therapies. TTO is a personalized procedure that can be tailored to the pathoanatomy of the patient based on physical examination and imaging. The complication rate associated with TTO strongly depends on the indication for surgery, the severity of the patient's condition, and the surgical approach. Despite the literature on TTO, to our knowledge, nosingle source has addressed the indications, techniques, outcomes, and complications of this procedure. The purpose of this article is to serve as such avaluable resource. Highlights from recent studies we would like to emphasize are two-fold. First, maintaining a distal cortical hinge yields lower complication rates than osteotomies involving complete tubercle detachment with classic or standard techniques. Second, based on current evidence, TTO consistently provides symptomatic relief, and most patients can return to work or sport at their pre-operative level within 3 and 6months, respectively. TTO is a personalizable surgical technique that may be utilized for multiple patellofemoral disorders and is associated with good outcomes.

Application of Functional Neurology Therapy in a Lactose-Intolerant Patient

This case report examines the impact of a single session of functional neurology on a 35-year-old female patient diagnosed with lactose intolerance. The patient presented with severe gastrointestinal symptoms, including frequent diarrhea, bloating, and vomiting upon dairy consumption. The intervention aimed to reset dysfunctional neurological programs believed to contribute to her condition. The study utilized a standardized lactose intolerance breath test to measure the hydrogen and methane levels at various intervals before and after treatment. Post-treatment results showed symptomatic relief with the patient reporting normalized bowel movements and the absence of previous symptoms. Despite these improvements, the biochemical markers at higher time points (150 and 175 min) post-treatment remained similar to the pre-treatment values, indicating persistent lactose malabsorption and highlighting the variability of hydrogen measurements. This case report suggests that a single session of functional neurology can significantly alleviate the symptoms of lactose intolerance. However, the preliminary nature of these results underscores the need for further research involving larger sample sizes and long-term follow-up to fully understand the treatment’s efficacy and underlying mechanisms.

Evaluating the protective effect of dapsone on experimental osteoarthritis models induced by MIA in male rats.

Osteoarthritis, a degenerative condition that results in significant morbidity, is typically managed with treatments aimed at symptom relief rather than addressing the underlying degeneration. Dapsone, recognized for its anti-inflammatory, antioxidant, antiexcitotoxic, and antiapoptotic properties, has demonstrated promising effects in various neurodegenerative diseases. This study explores the potential of dapsone to mitigate articular destruction, inflammation, and pain in rat models of osteoarthritis. Osteoarthritis was induced in rats by injecting MIA into the right knee joint. Dapsone was then administered intraperitoneally at 5, 10, or 20mg/kg every 2 days for 2 weeks. Behavioural tests were done on days 0, 7, and 14. On day 14, the articular cartilage was histologically analysed using H&E staining. Serum levels of NF-kB, IL-1β, and TNF-α were evaluated by ELISA. Dapsone effectively reduces pain, inflammation, and articular cartilage damage in osteoarthritis. Specifically, it improves mechanical allodynia and thermal hyperalgesia, reduces inflammatory markers (TNF-α, IL-1β, and NF-κB), and protects against cartilage destruction and chondrocyte loss, with the most significant effects at 20mg/kg. Dapsone effectively prevents pain, inflammation, and cartilage damage in osteoarthritis rats, suggesting its potential as a therapeutic option for managing osteoarthritis.

Physicians' knowledge, attitudes, and practices regarding fibromyalgia: A systematic review and meta-analysis of cross-sectional studies.

The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians' knowledge, attitudes, and practices regarding fibromyalgia. We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians' attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence. Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74-92), and half (51%; 95% CI, 40-62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45-89) versus general practitioners (38%, 95% CI, 24-54) (P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52-90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement. There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists.

Oculomotor nerve palsy caused by imidacloprid at initial diagnosis: A case report.

Amid the pervasive deployment of imidacloprid, the incidence of poisoning from this compound has risen markedly. Those afflicted with imidacloprid poisoning typically exhibit symptoms ranging from headaches, dizziness, nausea, and abdominal pain, to impaired consciousness and breathlessness, yet instances of ocular paralysis induced by this toxin have not previously been documented. When the pesticide spray inadvertently made contact with the patient's eyes, they were seared with a burning sensation and discomfort. Subsequent to this incident, on the second day, the individual began to experience diplopia in the right eye and found it arduous to elevate his eyelids, indicating a challenge in achieving full extension. Based on the medical history, symptoms, and signs, the patient was diagnosed with oculomotor nerve palsy caused by imidacloprid. The treatment involved intravenous dexamethasone to reduce inflammatory response in the eye tissue; oral pantoprazole enteric-coated tablets to suppress acid production and protect the stomach; Xuesaitong administered intravenously to improve blood supply to the eye and promote metabolism of toxins; vitamin C, cobamamide, and vitamin B1 for nerve nutrition and antioxidant effects; local application of tobramycin-dexamethasone eye drops for anti-inflammatory purposes; and repeated flushing of the conjunctival sac with saline. Finally, the patient improved and was discharged. After active treatment, the patient finally improved diplopia and ptosis. This report marks the first documentation of oculomotor nerve palsy induced by imidacloprid, featuring diplopia, and blepharoptosis without substantial limitation of ocular motility. Following therapeutic intervention, the patient showed marked improvement and was discharged from the hospital, providing a point of reference for the treatment of analogous cases in future clinical practice. It also serves as a reminder for the public to take appropriate precautions when using imidacloprid.

Enki’s Seven Sages (Adapa/Oannes and the Apkallu): Humanity’s Cosmic Guardians

In contrast to the cruel and militant gods, who treated humans as pawns in their power struggle, Enki is remembered not just as a benevolent god who saved the human race from extermination, but who also imparted knowledge. Especially scholarly disciplines like divination, astrology, astronomy, lamentation and exorcism were considered a revelation by Enki. The Catalogue of Texts and Authors attests that a handbook of medical symptoms comes “of the mouth of Ea”, “Adapa wrote them down at his dictation.” Enki was helped by his Seven Sages – the apkallu (Adapa being the main one) – the cosmic guardians who disseminated his knowledge, and were remembered as teachers of humankind and laying the foundation of civilization. According to Berossus, “from that time nothing further has been discovered.” Sometime around the Flood they disappeared, descending to the abode of Enki. This transition is reflected in the change from semi-divine sages or culture-heroes (apkallu) to scholars (ummanu).

The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

Skin complications during iron chelation therapy for beta-thalassemia: overview and treatment approach.

Thalassemia is an inherited genetic disorder of hemoglobin that affects a large population worldwide, and it is estimated that between 50,000 and 60,000 infants with thalassemia are born each year. The most common treatment for thalassemia is blood transfusion, which leads to iron overload. This in itself is a serious clinical condition, and is commonly managed with iron chelation therapy. However, iron chelators can cause various skin complications, including hyperpigmentation, skin rash, itching, and photosensitivity. These skin side effects can impact patients' quality of life. Therefore, this article provides a comprehensive overview of skin complications caused by iron chelators, along with a proposed comprehensive approach to their management in patients with beta-thalassemia. Key strategies include patient education, regular skin assessment, sun protection measures, symptomatic relief with topical corticosteroids and antihistamines, and consideration of treatment modification if severe complications occur. Collaboration between hematologists and dermatologists, along with psychological support and regular follow-up, is an essential component of this multidisciplinary approach. By implementing these strategies, healthcare providers can optimize skin care for patients with beta-thalassemia treated with iron chelators and improve their quality of life.

ESR Essentials: image guided drainage of fluid collections-practice recommendations by the Cardiovascular and Interventional Radiological Society of Europe.

This ESR Essentials article intends to provide detailed, step-by-step, information on the role of imaging in the diagnosis, procedural management, and follow-up of patients with fluid collections. Evidence-based medicine recommendations for the positioning of percutaneous drainages and/or for diagnostic/therapeutic aspiration of fluid collections are provided. Although medical history, clinical symptoms, physical examination, and laboratory tests can raise suspicions regarding a collection, an imaging assessment is usually necessary for the diagnosis. Radiologists can easily identify fluid collections that are clinically suspected by using a wide range of imaging modalities, such as ultrasound, CT, MRI, and cone-beam CT. Consequently, these imaging methods (either alone or combined), can be used to aspirate the collection or for the placement of a drainage catheter. The choice of imaging technique to be used is influenced by the location of the collection, operator preference, size, and content of the collection. In addition, it is of utmost importance to underline the role of the interventional radiologist in the management and follow-up of patients with percutaneous drains, in collaboration with surgeons, clinicians, and diagnostic radiologists. KEY POINTS: Indications for percutaneous imaging-guided drainage are supported by clinical findings, laboratory tests, and pre-procedural imaging. Deciding between aspiration or drain insertion should follow patient assessment and fluid collection characterization. The interventional radiologist should be part of the entire patient care process including follow-up.

Clinical impact of esophageal muscle thickness on peroral endoscopic myotomy patients.

Peroral endoscopic myotomy (POEM) is a standard procedure for achalasia, an esophageal motility disorder, characterized by a thickened lower esophageal sphincter muscularis propria (LEMP). Visualization of this anatomical stratification has been made possible by the advent of endoscopic ultrasound (EUS). However, the effect of LEMP thickness on treatment outcomes remains unclear. The objective of this study was to investigate whether LEMP thickness affects treatment response post-POEM. This was a single-center, prospective cohort study of patients who underwent POEM between 2014 and 2021. Patients who underwent EUS to evaluate the LEMP before POEM were included in the study. We divided the patients into two groups according to muscle thickness measured by EUS (≥ 2.80mm; group 1, < 2.80mm; group 2). The pre- and post-procedural clinical parameters were compared between the two groups. Among 278 patients, 189 were enrolled. There were no significant differences in the pre- and post-Eckardt scores, integrated relaxation pressure, and distensibility index between the two groups divided by muscle thickness. Furthermore, there was no statistically significant difference in symptom recurrence, as measured by an Eckardt score > 3, post-procedural complications, or post-POEM GERD symptoms. However, patients with thicker lower esophageal sphincter muscle showed a greater decrease in Eckardt scores (ΔES ≥ 3) which was statistically significant (P = 0.002). POEM is an effective and safe treatment method for achalasia, regardless of LES muscle thickness. There was a statistically significant difference in the decrease of Eckardt scores of 3 or greater (ΔES ≥ 3) after POEM in the thicker LEMP group suggesting greater alleviation of symptoms in POEM patients with thicker lower esophageal muscle.

Challenges and Advances in the Diagnosis and Management of Neurogenic Thoracic Outlet Syndrome: A Comprehensive Review.

Neurogenic thoracic outlet syndrome (nTOS) is caused by brachial plexus compression in the thoracic outlet. It accounts for 85%-95% of thoracic outlet syndrome (TOS) cases, which may also be caused by compression of the subclavian artery and vein. Compression occurs in the interscalene triangle, costoclavicular space or subpectoralis minor space, with congenital anomalies and repetitive overhead activities as contributing factors. Diagnosis is challenging due to overlapping symptoms with other conditions. Patients commonly report pain, numbness, tingling and weakness in the neck, shoulder and arm, exacerbated by arm elevation. Symptoms related to nTOS may manifest in the distribution of the upper (C5-C6), middle (C7) and lower plexus (C8-T1). Although widely used, provocative tests have varying degrees of sensitivity and specificity and may have high false-positive rates, complicating the diagnosis. Patterns on electrodiagnostic studies provide key diagnostic clues, such as reduced sensory response in the medial antebrachial cutaneous nerve and low compound motor action potential in the median nerve. Imaging techniques like magnetic resonance imaging (MRI), alongside procedures like diagnostic and therapeutic anterior scalene blocks, assist in identifying anatomical abnormalities and predicting surgical outcomes. Management of nTOS involves lifestyle changes, physical therapy, medication and botulinum toxin injections for symptomatic relief. Surgical options may include supraclavicular, transaxillary and infraclavicular approaches, each offering specific benefits based on patient anatomy and surgeon expertise. Minimally invasive techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic surgery, enhance exposure and dexterity, leading to better outcomes. Future research should focus on developing precise diagnostic tools, understanding nTOS pathophysiology, standardising diagnostic criteria and surgical approaches, comparing long-term treatment outcomes and exploring preventive measures to improve patient care and quality of life. Level of Evidence: Level V (Therapeutic).

A Cross-Sectional Evaluation of the Virtual Outpatient Management of People With Mpox.

To report on the implementation and outcomes of a virtual ward established for the management of mpox during the 2022 outbreak, we conducted a 2-center, observational, cross-sectional study over a 3-month period. All patients aged ≥17 years with laboratory polymerase chain reaction-confirmed monkeypox virus managed between 14 May and 15 August 2022, at the Hospital for Tropical Diseases at University College London Hospitals National Health Service (NHS) Foundation Trust and sexual health services at Central North and West London NHS Foundation Trust, were included. Main outcomes included the proportion of patients managed exclusively on the virtual ward, proportion of patients requiring inpatient admission, proportion of patients with human immunodeficiency virus, and duration of lesion reepithelialization. Among confirmed cases (N = 221), 86% (191/221) were managed exclusively on the virtual ward, while 14% (30/221) required admission. Treatment for concomitant sexually transmitted infections was provided to 25% (55/221) of patients, antibiotics for other infective complications to 16% (35/221), and symptomatic relief to 27% (60/221). The median time from onset to complete lesion reepithelialization and de-isolation was 18 days (range, 8-56 days). Eleven percent (24/221) of individuals disengaged from services within 4 days of testing. The virtual ward model facilitated safe and holistic outpatient management of mpox, while minimizing admissions. This approach could serve as a model for future outbreak responses.

Vitamin D Supplementation in Congenital Ichthyosis: A Case Series.

Ichthyosis is a group of genetic keratinization disorders characterized by excessive scaling that is associated with hyperproliferative epidermis and/or cellular retention. Whereas normal outer epidermis thickness is 25 μm, it can be 10-fold greater in patients with ichthyosis. As a result, photoactivation of 7-dehydrocholesterol is impaired, causing systemic vitamin D deficiency.In this case series, 25 patients with congenital ichthyosis with vitamin D deficiency (<10 ng/mL) were supplemented with 60,000 IU of vitamin D3 for 10 days followed by daily allowance of 400 to 600 IU of vitamin D3 and 40 mg/kg per day of elemental calcium. The authors assessed improvement in cutaneous scaling and body and tested patients' blood and urine samples at day 1, day 10, 1 month, and 3 months. They also documented patients' Dermatology Life Quality Index score before and after treatment.All patients had normal vitamin D levels; supplementation was discontinued for two patients who reached a level of 100 ng/mL within 10 days. Subjective improvement of symptoms (dryness of the skin, allergic rhinitis, tightness of the skin, and scaling) was observed by both the provider and the patients. There was remarkable improvement in symptoms of severe ichthyosis such as lamellar ichthyosis (tightness of the skin and scaling). Marked improvement in Dermatology Life Quality Index score was also noted.This case series demonstrated remarkable symptomatic relief with vitamin D supplementation in patients with congenital ichthyosis; however, additional research should be conducted with larger sample sizes to support these findings.

The Extent of Delay in Diagnosis, Treatment and their Associated Factors among Tuberculosis Patients Attending Government Hospitals of Rishikesh, Uttarakhand: A Cross-Sectional Study.

"Tuberculosis (TB) remains a major public health problem" worldwide, affecting almost all age groups. "Early diagnosis and prompt treatment are essential to significantly reducing the TB burden." However, a significant proportion of cases remain undiagnosed and untreated, which plays a vital role in the transmission of the disease and severity of the illness in the community in most developing countries. This study aimed to assess "the extent of delay in diagnosis and treatment of TB patients" and to identify the major factors associated with such delays (whether patient or health system-related) among TB patients in Rishikesh. This descriptive cross-sectional study was conducted in Rishikesh Town, Dehradun District, Uttara khand, India. Total of 130 newly diagnosed TB patients were recruited as study participants who attended the government hospitals of Rishikesh, All India Institute of Medical Sciences, Rishikesh and S P S Government Hospital, Rishikesh. A universal sampling technique was used in this study. The mean age of the study participant was 36.75 (Standard Deviation (SD), 17.6), and the median age was 34 years. Of the patients, 64.6% were men, and 35.4% were women. The extent of various delays, such as patient delay (median 16 days), diagnostic delay (median 78.5 days), treatment delay (median 4 days), health system delay (43 days), and total delay (median 81 days). The misconception of any chronic disease may lead to a false diagnosis or long treatment for symptomatic relief; the absence of proper diagnostic tests and doctor shopping could be the reasons for the prolonged diagnostic delay. Therefore, by strengthening the collaboration between private and public practitioners in order to meet the expectations of the Government of India to achieve the goals of the "National Strategic Plan for ending TB" in India by providing good quality care for all patients.

Eighteen-Month Real-World Experience Using Mavacamten for Treatment of Obstructive Hypertrophic Cardiomyopathy in a Racially Diverse Population.

Patients with obstructive hypertrophic cardiomyopathy have increased symptomatic burden. Mavacamten was recently approved for treatment of obstructive hypertrophic cardiomyopathy based on 2 randomized controlled trials. However, its use under real-world conditions and in diverse populations is under-studied. This was a prospective observational cohort study of patients seen at the Johns Hopkins HCM center and prescribed mavacamten for obstructive hypertrophic cardiomyopathy between July 7, 2022 and January 6, 2024. Patients were followed longitudinally, with serial echocardiography and clinical evaluation as mandated by the risk evaluation and mitigation strategy program. Sixty-six patients received mavacamten (mean age 59 years, 47% male, 29% non-White [Black, Hispanic/Latino, Asian, Native Hawaiian or Pacific Islander], 47% obese). Before treatment, all patients had New York Heart Association class II (51.5%) or III (48.5%) heart failure symptoms. Initial maximum peak left ventricular outflow tract gradient was 107±46 mm Hg. Median treatment duration was 9 months. For patients on mavacamten after ≥6 months (n=43), symptoms improved by ≥1 New York Heart Association class in 72% of patients, and peak left ventricular outflow tract gradient decreased by 80±46 mm Hg, eliminating hemodynamically significant left ventricular outflow tract obstruction in 79.1% of patients. Mavacamten was temporarily discontinued in 3 patients due to left ventricular ejection fraction decrease <50%. There were no medication-related adverse events. Effectiveness and safety were similar between White and non-White patients, but symptomatic relief was attenuated in patients with body-mass index ≥35 kg/m2. Mavacamten was effective and safe when used under real-world conditions in a racially diverse population of symptomatic patients with obstructive hypertrophic cardiomyopathy. Patients with comorbid obesity were less likely to experience symptomatic improvement while on mavacamten.

A cellular disease model toward gene therapy of TGM1-dependent lamellar ichthyosis

Lamellar Ichthyosis (LI) is a chronic disease, mostly caused by mutations in TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene edited cells showed complete absence of Transglutaminase-1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a SINγ-RV vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity and cornified envelopes formation, hence restored proper epidermal architecture. Single cell multiomic analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial to epidermal regeneration. This study serves as a proof-of-concept for assessing the potential of this therapeutic approach in treating TGM1 dependent LI.