FUSE-ML: development and external validation of a clinical prediction model for mid-term outcomes after lumbar spinal fusion for degenerative disease

Background: Indications and outcomes in lumbar spinal fusion for degenerative disease are notoriously heterogenous. Selected subsets of patients show remarkable benefit. However, their objective identification is often difficult. Decision-making may be improved with reliable prediction of long-term outcomes for each individual patient, improving patient selection and avoiding ineffective procedures. Methods: Clinical prediction models for long-term functional impairment [Oswestry Disability Index (ODI) or Core Outcome Measures Index (COMI)], back pain, and leg pain after lumbar fusion for degenerative disease were developed. Achievement of the minimum clinically important difference at 12 months postoperatively was defined as a reduction from baseline of at least 15 points for ODI, 2.2 points for COMI, or 2 points for pain severity. Results: Models were developed and integrated into a web-app ( https://neurosurgery.shinyapps.io/fuseml/ ) based on a multinational cohort [N = 817; 42.7% male; mean (SD) age: 61.19 (12.36) years]. At external validation [N = 298; 35.6% male; mean (SD) age: 59.73 (12.64) years], areas under the curves for functional impairment [0.67, 95% confidence interval (CI): 0.59-0.74], back pain (0.72, 95%CI: 0.64-0.79), and leg pain (0.64, 95%CI: 0.54-0.73) demonstrated moderate ability to identify patients who are likely to benefit from surgery. Models demonstrated fair calibration of the predicted probabilities. Conclusions: Outcomes after lumbar spinal fusion for degenerative disease remain difficult to predict. Although assistive clinical prediction models can help in quantifying potential benefits of surgery and the externally validated FUSE-ML tool may aid in individualized risk-benefit estimation, truly impacting clinical practice in the era of "personalized medicine" necessitates more robust tools in this patient population. Keywords: Clinical prediction model; Machine learning; Neurosurgery; Outcome prediction; Predictive analytics; Spinal fusion

TRATAMENTO CRÔNICO COM DECANOATO DE NANDROLONA PROMOVE REMODELAMENTO CARDÍACO E ALTERAÇÃO DA FUNÇÃO VENTRICULAR ESQUERDA EM RATAS: PAPEL DOS MODULADORES INTRACELULARES DE Ca2+

O uso dos esteróides anabólicos androgênicos (EAA) tem crescido consideravelmente nas últimas décadas, sendo utilizada tanto por homens como por mulheres, com redução significativa na idade inicial destes utilizadores. O uso abusivo e indiscriminado destes hormônios acarreta alterações cardiovasculares, como hipertrofia cardíaca associada com deposição de colágeno, considerada patológica. Este remodelamento cardíaco causado pelos EAA pode desencadear hipertensão, insuficiência cardíaca congestiva, cardiomiopatia, arritmias e até morte súbita. O uso de EAA é geralmente realizado em associação com o exercício físico, que isoladamente promove efeitos cardiovasculares benéficos, todavia em associação perde-se o efeito benéfico do exercício, com a ocorrência de adaptações cardiovasculares desfavoráveis e função ventricular comprometida, especialmente função diastólica, fibrose miocárdica e desarranjo de cardiomiócitos. Além disso, pouco se sabe sobre os efeitos cardiovasculares dessas drogas no sexo feminino. Este trabalho objetiva avaliar os efeitos do decanoato de nandrolona (DN) e do exercício físico resistido sobre a contratilidade cardíaca em ratas. Os animais foram separados em quatro grupos: C (não treinados); CE (submetidos a exercício físico resistido em água, cinco vezes por semana); ND (tratados com DN, 20 mg/kg/semana durante quatro semanas); e NDE (treinados e tratados). Os parâmetros hemodinâmicos (+dP/dtmáx, -dP/dtmin e Tau) foram avaliados no ventrículo esquerdo. O coração foi coletado para análise histológica (H&E) e deposição de colágeno (picrosírius red). A análise da expressão das proteínas relacionadas com o transiente de Ca2+ citosólico foi realizada pelo método de Western blot. Os animais tratados com DN e os animais submetidos ao treinamento físico resistido apresentaram aumento na contratilidade e relaxamento cardíaco. Além disso, o DN promoveu aumento na expressão da fosfolambam fosforilada (p-PLB) e isoforma do retículo sarcoplasmático ATPase 2 (SERCA-2a), enquanto o exercício de resistência aumentou a fosforilação de PLB e a expressão do trocador de Na+/Ca2+ (NCX). O remodelamento cardíaco patológico, característico pela hipertrofia cardíaca associada com deposição de colágeno, foi observado após o tratamento com DN. Portanto, tratamento com DN e o exercício físico resistido em fêmeas, por um período de quatro semanas, foram capazes de promover hipertrofia cardíaca e aumentar a função cardíaca, alterando proteínas responsáveis pela regulação de Ca2+ intracelular, entretanto, a hipertrofia causada pela nandrolona foi considerada patológica. Certamente, esta avaliação comparando o uso de nandrolona e a contratilidade cardíaca deve ser posteriormente investigada, especialmente com uso mais prolongado, visto que as exacerbações prolongadas desses efeitos podem desencadear complicações cardíacas graves

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases

PURPOSE The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. METHODS We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. RESULTS A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. CONCLUSION Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory

Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.

Importance Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies. Objective To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure. Design, Setting, and Participants A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021. Interventions Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475). Main Outcomes and Measures The primary outcome was a composite of tracheal intubation or mortality within 30 days. Results The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group. Conclusions and Relevance Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings. Trial Registration isrctn.org Identifier: ISRCTN16912075