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Kidney Medicine Jun 2024Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for...
RATIONALE & OBJECTIVE
Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist (DEARA) examined in the ongoing phase 2 DUET trial for focal segmental glomerulosclerosis (FSGS). In the DUET 8-week double-blind period, sparsentan resulted in greater proteinuria reduction versus irbesartan. We report the long-term efficacy and safety of sparsentan during the open-label extension over more than 4 years.
STUDY DESIGN
Patients were examined from their first sparsentan dose (double-blind period or open-label extension) through 4.6 years.
SETTING & PARTICIPANTS
Patients with FSGS, excluding secondary FSGS.
INTERVENTION
Sparsentan (200, 400, and 800 mg/d).
OUTCOMES
Urinary protein-creatinine ratio, FSGS partial remission endpoint (urinary protein-creatinine ratio ≤1.5 g/g and >40% reduction from baseline), estimated glomerular filtration rate, and blood pressure approximately every 12 weeks. Treatment-emergent adverse events by year and cases/100 patient-years.
RESULTS
109 patients were enrolled; 108 received ≥1 sparsentan dose; 103 entered the open-label extension (68 sparsentan, 35 irbesartan during the double-blind period). Sparsentan was ongoing in 45/108 patients (41.7%); median time to treatment discontinuation was 3.9 years (95% CI, 2.6-5.2). Mean percent proteinuria reduction from baseline was sustained through follow-up. Achieving partial remission within 9 months of first sparsentan dose (52.8% of patients) versus not achieving (47.2%) was associated with significantly slower rate of estimated glomerular filtration rate decline over the entire treatment period (-2.70 vs -6.56; = 0.03) and in the first 2 years (-1.69 vs -6.46; = 0.03). The most common treatment-emergent adverse events (>9 cases/100 patient-years) were headache, peripheral edema, upper respiratory infection, hyperkalemia, and hypotension. Peripheral edema and hypotension declined from year 1 (13.9% and 15.7% of patients, respectively) to ≤4% in years ≥2. There were no cases of heart failure and no patient deaths.
LIMITATIONS
The open-label extension does not include a comparison group.
CONCLUSIONS
Long-term sparsentan treatment showed sustained proteinuria reduction and a consistent safety profile.
PubMed: 38831932
DOI: 10.1016/j.xkme.2024.100833 -
Journal of Addictions Nursing
Topics: Humans; Naloxone; Narcotic Antagonists; Pulmonary Edema; Edema; Male; Adult
PubMed: 38830001
DOI: 10.1097/JAN.0000000000000579 -
Frontiers in Pain Research (Lausanne,... 2024Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial... (Review)
Review
Complex Regional Pain Syndrome (CRPS) is a chronic pain disorder characterized by a diverse array of symptoms, including pain that is disproportionate to the initial triggering event, accompanied by autonomic, sensory, motor, and sudomotor disturbances. The primary pathology of both types of CRPS (Type I, also known as reflex sympathetic dystrophy, RSD; Type II, also known as causalgia) is featured by allodynia, edema, changes in skin color and temperature, and dystrophy, predominantly affecting extremities. Recent studies started to unravel the complex pathogenic mechanisms of CRPS, particularly from an autoimmune and neuroimmune interaction perspective. CRPS is now recognized as a systemic disease that stems from a complex interplay of inflammatory, immunologic, neurogenic, genetic, and psychologic factors. The relative contributions of these factors may vary among patients and even within a single patient over time. Key mechanisms underlying clinical manifestations include peripheral and central sensitization, sympathetic dysregulation, and alterations in somatosensory processing. Enhanced understanding of the mechanisms of CRPS is crucial for the development of effective therapeutic interventions. While our mechanistic understanding of CRPS remains incomplete, this article updates recent research advancements and sheds light on the etiology, pathogenesis, and molecular underpinnings of CRPS.
PubMed: 38828388
DOI: 10.3389/fpain.2024.1385889 -
Actas Dermo-sifiliograficas May 2024The benefit of lower limb compression therapy is not limited to chronic venous insufficiency or/and lymphoedema. Thanks to its anti-edema and anti-inflammatory effects,... (Review)
Review
The benefit of lower limb compression therapy is not limited to chronic venous insufficiency or/and lymphoedema. Thanks to its anti-edema and anti-inflammatory effects, compression therapy is considered a beneficial adjuvant therapy to treat atypical wounds, inflammatory dermatoses, cellulitis, and traumatic wounds in the absence of contraindications. Strict contraindications are limited to severe peripheral arterial disease and decompensated heart failure. The variability of commercially available compression materials and systems, such as short-stretch bandages, multi-component systems, zinc oxide bandages, medical adaptive compression systems, ulcer compression stockings or medical compression stockings, facilitates the adaptation of compression therapy to the individual needs of each patient. Compared to venous leg ulcers, low pressures of 20mmHg are often sufficient to treat dermatological disorders, with higher patient tolerance and compliance.
PubMed: 38821356
DOI: 10.1016/j.ad.2024.05.012 -
Clinical and Experimental Rheumatology May 2024This study aimed to evaluate the clinical significance of the coexistence of 2 or more myositis-specific antibodies (multiple MSAs) in adult patients with idiopathic...
OBJECTIVES
This study aimed to evaluate the clinical significance of the coexistence of 2 or more myositis-specific antibodies (multiple MSAs) in adult patients with idiopathic inflammatory myopathies (IIM).
METHODS
We assessed a cohort of 202 consecutive patients with IIM. Clinical features and survival rates were compared between patients with and without multiple MSAs.
RESULTS
Of those 202 patients, 44 (21.8%) were found to have multiple MSAs. 63.6% of the 44 patients tested positive for anti-aminoacyl-tRNA synthetase antibodies (anti-ARS+) and 52.3% positive for anti-melanoma differentiation-associated protein-5 antibody (anti-MDA5+). The presence of multiple MSAs was associated with less rapidly progressive interstitial lung disease (RP-ILD), fever, rash, periungual erythema, more muscle involvement and dysphagia, higher albumin level, and higher positive rate of ANA antibody in anti-MDA5+ population. In anti-ARS+ population with multiple MSAs, there were more V-neck sign, skin ulcers, dysphagia and peripheral edema. No differences in survival rates were observed between patients with or without multiple MSAs in the overall and anti-ARS+ populations. However, the survival rate in anti-MDA5+ population with multiple MSAs was significantly higher than those without multiple MSAs (p = 0.003). Moreover, multiple MSAs remained an independent protective factor against mortality in multivariable Cox regression analysis of anti-MDA5+ population [HR 0.108 (95% CI 0.013, 0.908), p=0.041].
CONCLUSIONS
Multiple MSAs coexist in some IIM patients and their existence indicates mixed features from concomitant MSAs in anti-MDA5+ population and anti-ARS+ population. Identifying multiple MSAs could help to discover a more favourable disease phenotype with decreased mortality in anti-MDA5+ population.
PubMed: 38819961
DOI: 10.55563/clinexprheumatol/22j41g -
Physiology International Jun 2024This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with...
This study explored the effects of fructose-induced obesity and metabolic disorders on peripheral inflammatory hyperalgesia, employing quantitative sensory testing with the von Frey test and measuring paw edema to assess inflammatory responses. Wistar rats were administered water or 10% fructose solution ad libitum over a period of 5 weeks. After intraplantar administration of inflammatory agents such as carrageenan (1 mg/paw), lipopolysaccharide (LPS; 100 µg/paw), or prostaglandin E2 (PGE2, 100 ng/paw), we conducted mechanical hyperalgesia tests and paw edema evaluations. The fructose diet resulted in dyslipidemia, elevated insulin and leptin plasma levels, insulin resistance, and increased epididymal and retroperitoneal adiposity compared to control animals. In response to inflammatory agents, the fructose group displayed significantly enhanced peripheral hyperalgesia and more pronounced paw edema. Our results demonstrate that fructose not only contributes to the development of obesity and metabolic disorder but also exacerbates peripheral inflammatory pain responses by enhancing prostaglandin sensitivity.
Topics: Animals; Fructose; Rats, Wistar; Male; Hyperalgesia; Rats; Inflammation; Metabolic Diseases; Obesity; Carrageenan; Dinoprostone; Edema; Insulin Resistance; Lipopolysaccharides; Disease Models, Animal
PubMed: 38819928
DOI: 10.1556/2060.2024.00376 -
Cureus Apr 2024Leprosy has been known for its wide range of peripheral nerve and tissue involvement and causing disabilities. Early diagnosis and treatment with multi-drug therapy can...
Leprosy has been known for its wide range of peripheral nerve and tissue involvement and causing disabilities. Early diagnosis and treatment with multi-drug therapy can save lives and limbs and prevent disabilities. However, management and drug therapy are usually lengthy and full of ups and downs of side effects. Further, the lepra reaction is frequently noted during management, requiring immunosuppression and leading to associated side effects. Limb edema per se due to leprosy is unusual and mostly a symptom of a reactional state. There is no specific management for edema in such cases, and it subsides with improving reactionary states. Nevertheless, the edema may be persistent and bothersome. The present report highlights one such unusual case in a 40-year-old man, diagnosed with borderline-tuberculoid leprosy and experiencing a type-1 reaction. Owing to ocular complications, steroid therapy for the reaction was tapered abruptly, and his limb edema did not subside with the improving lepra reaction. Compression stockings helped to manage edema. This case also makes us ponder the possible use of compression stockings as an opioid-sparing aid in lepra reaction-related edema.
PubMed: 38800266
DOI: 10.7759/cureus.58893 -
Journal of Orthopaedic Case Reports May 2024Buerger's disease is common in 74.70% of cases in the lower limb but in 20.20% of cases, it is found in the upper limb or hand. The disease usually starts from pain in...
INTRODUCTION
Buerger's disease is common in 74.70% of cases in the lower limb but in 20.20% of cases, it is found in the upper limb or hand. The disease usually starts from pain in the finger/thumb or hand and then to more centrally.Patients presented with pain in the hand with gangrene of fingers. Pain aggravated on lifting hand above the shoulder level or above heart level in upright or lying in the bed, respectively.
CASE REPORT
In almost all patients, there was a history of smoking except one and all patients had involvement of digits of the right or left hand. Diagnosis of Buerger's disease was made based on the history of smoking, weak or absent pulse, lack of bleeding, swelling, edema, blackening, stony hard fingers or thumb on clinical examination, and color Doppler study of the limb.In all patients, Stellate ganglion chemical neurolysis with 8% phenol was done at C7-T1 under fluoroscopic and radiocontrast dye (Iohexol 300) guidance.After successful neurolysis patients got excellent pain relief, their wounds started healing, the vascularity of the diseased part increased and the disease stopped progressing.
CONCLUSION
Stellate ganglion chemical neurolysis with phenol in Peripheral vascular disease or Buerger's disease of hand is an effective method to stop the disease procession, promoting wound healing, controlling ischemic pain, and avoiding surgical amputation.
PubMed: 38784893
DOI: 10.13107/jocr.2024.v14.i05.4468 -
Ophthalmology. Retina May 2024Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare genetic (CAPN5) autoimmune condition typically diagnosed in adulthood and characterized...
PURPOSE
Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is a rare genetic (CAPN5) autoimmune condition typically diagnosed in adulthood and characterized by a triad of inflammation, retinal degeneration and neovascularization. We report novel multimodal imaging findings in children and young adults with ADNIV and early treatment response to short-duration local and/or systemic corticosteroids.
DESIGN
Retrospective consecutive case series.
PARTICIPANTS
Ten patients under the age of 25 with ADNIV and available multimodal imaging.
METHODS
The medical records of patients under the age of 25 with a diagnosis of ADNIV with ultra-widefield fluorescein angiography (UWFFA) and optical coherence tomography (OCT) data were reviewed.
MAIN OUTCOME MEASURES
UWFFA and OCT findings at baseline and following local corticosteroids.
RESULTS
Median age at presentation was 14 years (range 9-24 years). OCT on presentation demonstrated CME in 8/20 eyes and symptomatic vitreoretinal interface disease in 2/20 eyes. Initial UWFFA demonstrated retinal vascular leakage (20/20 eyes, 100%), peripheral non-perfusion (13/20 eyes, 65%), and retinal neovascularization (6/20 eyes, 30%). Retinal vascular leakage improved with local corticosteroids and neovascularization regressed with anti-VEGF therapy.
CONCLUSIONS
UWFFA findings of prefibrotic ADNIV reported in adults were also present in children and young adults. Early testing for a pathogenic CAPN5 variant in at-risk children and regularly scheduled screening for uveitis and retinal vasculitis with UWFFA and OCT may prompt earlier intervention. Short duration local steroids are effective at treating retinal vascular leakage and macular edema but are not durable suggesting a potential role for steroid-sparing immunosuppressive therapy. Early treatment may alter the natural history of disease.
PubMed: 38782117
DOI: 10.1016/j.oret.2024.05.010 -
Ocular Immunology and Inflammation May 2024To evaluate outcomes of intravenous (IV) tocilizumab (TCZ) in patients with pars planitis refractory to conventional immunomodulatory therapy and anti-tumor necrosis...
PURPOSE
To evaluate outcomes of intravenous (IV) tocilizumab (TCZ) in patients with pars planitis refractory to conventional immunomodulatory therapy and anti-tumor necrosis factor (TNF) alpha agents.
METHODS
Medical records of eight patients diagnosed with pars planitis and treated with monthly 4 or 8 mg/kg IV TCZ were reviewed. The primary objective was to initiate and sustain remission continuously for three consecutive months. Secondary outcome measures were changes in best corrected visual acuity (BCVA), degree of anterior chamber (AC) inflammation, vitreous cell, vitreous haze, presence of vitreous or pars plana exudates, peripheral vasculitis, fluorescein angiography (FA) score and central subfieldthickness (CST) on macular optical coherence tomography (OCT).
RESULTS
Fourteen eyes of eight patients were treated with IV TCZ. Seven patients were women. The average age was 31.35 ± 16.42 years. In 6 (75%) out of 8 patients, IV TCZ, either as monotherapy or in combination with another conventional immunomodulatory agent, induced and sustained remission. The average FA score reduced from 11.15 ± 3.52 at the baseline visit to 6.50 ± 2.12 at the one-year follow-up visit (p-value < 0.05). None of the patients experienced any side effects of IV TCZ.
CONCLUSION
IV Tocilizumab (TCZ) may represent an effective and safe treatment option for patients diagnosed with pars planitis resistant to conventional immunomodulatory therapy and anti-TNF alpha agents.
PubMed: 38781578
DOI: 10.1080/09273948.2024.2354751