Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Congenital lacrimal sac fistula: intraoperative visualization by polyvinyl siloxane cast.

We report the intraoperative use of polyvinyl siloxane impression material to demonstrate the anatomy of the lacrimal sac, canaliculi, and lacrimal duct in a case of congenital lacrimal sac fistula. A 1-week-old boy was examined for tearing since birth. Examination revealed a left congenital lacrimal sac fistula. After a failed surgery to close the fistula with silicone intubation at 6 months of age, the patient underwent endonasal dacryocystorhinostomy performed at 14 months of age, aided by intraoperative injection of polyvinyl siloxane (trade name Reprosil) to mark and protect the nasolacrimal sac and facilitate endonasal visualization. A polyvinyl siloxane cast demonstrated the anatomy of the accessory canaliculus causing nasolacrimal duct obstruction. Postoperatively, the epiphora resolved and the fistula remained closed. The polyvinyl siloxane cast provides a 3-dimensional "ex vivo " model of the lacrimal sac, upper duct, and canalicular anatomy, and can be used in dacryocystorhinostomy surgery to identify and protect the lacrimal sac.

Long-term efficacy of biomodeled polymethyl methacrylate implants for orbitofacial defects.

OBJECTIVE: To report the long-term efficacy of custom polymethyl methacrylate implants using high-resolution computed tomographic modeling in the reconstruction of complex orbitofacial defects secondary to trauma. METHODS: Nine patients with complex orbitofacial bone defects after trauma were evaluated for this retrospective, nonrandomized, noncomparative study. All the patients underwent reconstruction using custom, heat-cured polymethyl methacrylate implants. Patients were followed up postoperatively and evaluated for complications. RESULTS: Nine consecutive patients (5 men and 4 women) aged 28 to 63 years who underwent surgical reconstruction using prefabricated, heat-cured polymethyl methacrylate implants were included in the study. The interval between injury and presentation ranged from 1 month to 40 years. There were no significant complications, including infection, extrusion, or displacement of the implant. In all of the patients, wound healing was uneventful, with antibiotic drugs administered perioperatively. Mean follow-up was 4.3 years from the first visit (range, 6 months to 10 years). CONCLUSIONS: Computed tomographic biomodeled, prefabricated, heat-cured polymethyl methacrylate implants are well tolerated in the long term. Their advantages include customized design, long-term biocompatibility, and excellent aesthetic results.

Mutational analysis of conserved amino acids in the T cell receptor alpha-chain transmembrane region: a critical role of leucine 112 and phenylalanine 127 for assembly and surface expression.

Correct assembly of all TCR complex polypeptides is essential for its cell surface expression and function. The transmembrane region of the TCRalpha chain is highly conserved and to gain insight into the structural and functional role of these residues, single amino acid substitutions were introduced and surface expression and signaling ability studied in T hybridoma cells. Introduction of acid residues within the TCRalpha chain transmembrane region were mostly tolerated, indicating that the net charge within this region of the TCR complex is not crucial to either assembly or signaling. However, mutations of leucine 112 or phenylalanine 127 to aspartic acids (L112D or F127D, respectively) resulted in dramatic loss of surface expression and, therefore, their signaling ability. Intracellular flow cytometry showed that the mutant TCRalpha polypeptides were present at levels comparable to wild-type, indicating that the reduced surface expression was not a consequence of impaired protein survival. The defect was characterized by immunoprecipitation and showed that residues L112 and F127 were involved in early interactions with the CD3 complex. A large proportion of the TCRalpha chain mutants L112D and F127D consisted of immature protein, indicative of a problem during early assembly of the TCR. Our findings provide evidence for the involvement of the conserved L112 and F127 residues of the TCRalpha chain transmembrane region in the assembly process of the TCR complex.