RESUMO
Background: Treatment-limiting severe cutaneous adverse reactions (SCAR) occur more commonly amongst persons with HIV-associated tuberculosis (TB). The impact of SCAR on long-term HIV/TB outcomes is unknown. Methods: Patients with TB and/or HIV admitted to Groote Schuur Hospital, Cape Town, South Africa with SCAR between 1/10/2018 and 30/09/2021 were eligible. Follow-up data was collected for 6- and 12-month outcomes: mortality, TB and antiretroviral therapy (ART) regimen changes, TB treatment completion, and CD4 count recovery. Results: Forty-eight SCAR admissions included: 34, 11, and 3 HIV-associated TB, HIV-only and TB-only patients with 32, 13 and 3 cases of drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome/toxic epidermal necrolysis and generalised bullous fixed-drug eruption respectively. Nine (19%), all HIV-positive (eight co-infected with TB), were deceased at 12-months, and 12(25%) were lost to follow-up. Amongst TB-SCAR patients, seven (21%) were discharged on all four first-line anti-TB drugs (FLTD), while 12(33%) had regimens with no FLTDs; 24/37(65%) completed TB treatment. Amongst HIV-SCAR patients, 10/31(32%) changed ART regimen. If retained in care (24/36), median (IQR) CD4 counts increased at 12-months post-SCAR (115(62-175) vs. 319(134-439) cells/uL). Conclusion: SCAR admission amongst patients with HIV-associated TB results in substantial mortality, and considerable treatment complexity. However, if retained in care, TB regimens are successfully completed, and immune recovery is good despite SCAR.
RESUMO
OBJECTIVES: Recovery of injured peripheral nerves depends on a balance between Schwann cell regeneration and scar formation. Transforming growth factor-beta1 (TGF-beta1) has been implicated as a humoral stimulus in scar formation. The neutralization of TGF-beta1 has been beneficial in the reduction of fibrosis. This study was to identify the presence of TGF-beta1 in regenerating peripheral nerve and to measure motor nerve regeneration by the neutralization of TGF-beta1 in neural wounds. STUDY DESIGN: A randomized study of rat sciatic nerve regeneration. METHOD: Sciatic nerve axotomy was performed, followed by serial immunohistochemical staining by anti-TGF-beta1 at 12 to 216 hours (n = 5). Two groups (n = 10) with sciatic axotomy and epineural repair were treated with a 7-day perineural administration of neutralizing antibody of TGF-beta1 or saline carrier via subcutaneous silicone infusion port. A control group (n = 10) without axotomy with anti-TGF-beta1 administration was established. At 12 weeks the compound muscle action potential amplitude (CMAP) and the muscle twitch strength generated by the gastrocnemiussoleus muscle complex were measured. RESULTS: TGF-beta1 was qualitatively present with maximal concentration by 72 to 144 hours. CMAP amplitude in the anti-TGF-beta1/axotomy group was 49.6% of the control and the axotomy/saline group was 31% of the control. Muscle twitch strength was 74% and 46.5%, respectively. These differences were statistically significant, P = .05. CONCLUSIONS: The presence of TGF-beta1 at regenerating nerve sites was confirmed. The benefit of neutralization of transforming growth factor on CMAP and muscle twitch strength was shown. These results suggest improved regeneration at nerve injury sites with neutralization of TGF-beta1.