Abstract Background and aims Sovateltide, an endothelin-B receptor agonist, has shown favorable functional outcomes in acute ischemic stroke (AIS) and is approved in India as a first-in-class therapy for AIS. A phase 4 study (NCT05955326) is currently recruiting patients in India (target N=160) to further assess safety and effectiveness. This report presents the results of a prespecified interim analysis conducted after enrollment of 80 patients. Methods Eligible participants were adults aged 18 to 78 years with radiologically confirmed AIS and an NIHSS score of 6 or higher, presenting within 24 hours of symptom onset. Exclusion criteria included intracranial hemorrhage and receipt of endovascular therapy. Participants were randomized to receive either normal saline or sovateltide (0.3 μg/kg), administered intravenously in three doses at 3±1 hour intervals on days 1, 3, and 6. Analyses were conducted in the intention-to-treat population, with missing endpoints imputed using MICE. Results Patient age and body weight, sex distribution, NIHSS score (p=0.5216), comorbidities, and the median time from symptom onset to first dose (16–18 hours) were comparable between groups. At 90 days, the sovateltide group (92.3%) of patients with mRS 0-2, showed greater improvement (OR 8.50, 95% CI 2.44-29.01; p=0.0005) than the control group (58.5%). Sovateltide group had more patients (84.62%) with improvement of ≥2 mRS points from baseline (Odds 5.24, 95% CI 1.85-15.50; p=0.0014) than control (51.22%). Ordinal shift analysis of mRS also favored sovateltide by 33% compared to control. Conclusions Sovateltide was associated with significantly improved 90-day functional outcomes, consistent with results from previous AIS efficacy trials. Conflict of interest
Odontogenic keratocyst (OKC) is an aggressive cystic lesion that arises from remnants of dental lamina. It mostly affects the mandibular posterior region and is commonly associated with an impacted tooth. Radiologically, it can present as unilocular or multilocular radiolucency with a sclerotic border, causing cortical plate expansion and even sometimes leading to perforation. The occurrence of multiple OKCs is considered the initial presentation of many syndromes. However, cases of multiple OKCs have also been reported in non-syndromic patients. We present a case of 17/M with a complaint of swelling in the mandibular anterior region. CBCT revealed three unilocular expansile lytic lesions in the mandible: a large lesion extending from tooth 46 (mandibular right first molar) to tooth 34 (mandibular left first premolar), along with separate lesions associated with teeth 38 and 48 (mandibular left and right third molar regions). Incisional biopsy was suggestive of OKC. So, cyst enucleation was done under general anaesthesia and histopathology showed a cystic lumen lined by OKC lining. Numerous daughter cysts were also seen. This case emphasises that the occurrence of multiple OKCs warrants evaluation for possible associated syndromes. Syndromic OKCs typically present at a younger age, show equal involvement of the maxilla and mandible, and demonstrate a higher recurrence rate compared to sporadic cases. Therefore, long-term follow-up is essential to achieve favorable outcomes, and management of such lesions requires a multidisciplinary approach.
Severe acute malnutrition (SAM) remains a growing public health concern in India, with increasing prevalence in recent national surveys. It is associated with impaired growth, neurodevelopmental deficits, and heightened infection risk. Inflammation and oxidative stress play central roles in its pathogenesis and mortality. Vitamin D (VD) has immunomodulatory and antioxidant effects, but its impact on inflammatory mediators and their regulators in SAM is poorly understood, with limited mechanistic evidence from human studies. Peripheral blood mononuclear cells (PBMC) were isolated from 10 participants suffering from uncomplicated SAM. The PBMCs were treated with VD for a period of 24 h following which the mRNA expression of inflammatory markers (TNFα IFN γ), their modulators (SOCS1 SOCS3) and PINK1 was measured by qPCR. Mean age of the participants was 30 ± 12 months. Following VD treatment, we noted a 2.4-fold decrease in mRNA expression of TNFα, 4.4-fold decrease in mRNA expression of IFN γ, 1.4-fold and 1.6-fold increase in mRNA expression of SOCS1 and SOCS3 compared to untreated ones (controls). No difference in mRNA expression of PINK1 was observed in the two group of cells. Vitamin D treatment is associated with a decreased expression of pro-inflammatory cytokines (TNF-α and IFN-γ) and a concomitant increase in expression of immunoregulatory genes SOCS1 and SOCS3 in PBMCs isolated from children suffering from uncomplicated SAM.
Maxillary defects resulting from oncologic resection, severe trauma, or invasive infections such as mucormycosis present significant reconstructive challenges due to the need to restore midfacial support, oral competence, speech, mastication, and facial aesthetics. Microvascular osteocutaneous free flaps have expanded reconstructive options by providing vascularized bone and soft tissue for simultaneous restoration of structural support and intraoral lining. This report describes our reconstructive experience in three patients who underwent microvascular reconstruction of complex maxillary defects at our institution over a two-year period. Etiologies included invasive mucormycosis in one patient and oncologic resection in two patients. Defects were classified according to the revised Brown classification, with one type IIIb defect involving the maxilla and orbital floor and two type V defects involving the maxilla and adjacent midfacial structures. Reconstruction was performed using free fibula osteocutaneous flaps in two patients and a radial forearm osteocutaneous flap in one patient, selected according to defect characteristics and tissue requirements. Bony segments were contoured to recreate the maxillary framework, while skin paddles were used for intraoral lining and oral-nasal separation. All flaps survived completely, with satisfactory healing, restoration of midfacial contour and support, preservation of oral competence and speech, and acceptable facial symmetry. Minor secondary contouring procedures were required in selected patients. No flap failures, major complications, or significant donor-site morbidity were observed. This case series demonstrates the application of osteocutaneous free flaps in the reconstruction of complex maxillary defects and highlights important technical considerations and the use of an algorithmic approach in flap selection based on the revised Brown classification.
