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Abstract Objective This study aims to investigate the feasibility and effectiveness of enhanced recovery after surgery (ERAS) in HIV-positive patients diagnosed with osteonecrosis of the femoral head (ONFH) undergoing total hip replacement (THR). Methods We retrospectively included 80 HIV-positive patients diagnosed with ONFH who underwent THR between 2011 and 2022. Forty patients treated before August 2019 constituted the control group, receiving standard antiviral regimens and traditional perioperative management pathways. The remaining 40 patients, treated after August 2019, formed the study group, which followed the ERAS protocol. This protocol emphasized the use of more effective antiviral medications, rapid viral load reduction, immune enhancement, improved nutritional status, control of co-infections, prophylactic antibiotics, and anti-osteoporosis measures. We recorded patients' general status and imaging examinations before surgery, as well as detailed perioperative management strategies, antiviral regimens, durations, and immunological indicators for both groups. Targeted and standardized treatment measures were applied to the ERAS group, allowing for a comparison of the efficacy of perioperative management between the two patient groups. Results Preoperative nutritional and immune indicators were lower in the control group than in the study group, while inflammatory markers were higher. Postoperatively, immune, nutritional, and inflammatory indicators were significantly better in the ERAS group compared to the control group. Following antiviral treatment, the viral load was predominantly undetectable in the ERAS group (target not detected, TND). Comprehensive measures minimized complications in the ERAS group (P = 0.028, P |