The Impact of Author Financial Conflicts on Robotic-Assisted Joint Arthroplasty Research

BackgroundRecent studies have suggested clinical superiority with robotic-assisted arthroplasty compared to traditional techniques. However, concerns exist regarding the author’s financial conflicts of interest (COI), which may influence research outcomes. This study aimed to determine whether COI relating to robotic-assisted arthroplasty influences the results of published outcomes following total hip (THA), total knee (TKA), and unicompartmental knee arthroplasty (UKA).MethodsWe performed a systematic review to identify all studies evaluating the use of robotics in THA, TKA, and UKA. An author’s financial COI was identified if they reported a relevant disclosure through the American Academy of Orthopedic Surgeons or within the study article. We then queried the Open Payments website to record all payments made from a robotic company in the year prior to publication. Each study was categorized as either favoring robotics (n = 42), neutral (n = 10), or favoring traditional techniques (n = 2). We then compared the number of conflicted authors, journal impact factor, level of evidence, and mean annual industry payment to each author.ResultsOf the 54 studies meeting inclusion criteria, 49 (91%) had an author financial COI. Conflicted studies were more likely to report favorable results of robotics than nonconflicted studies. When compared to studies favoring conventional techniques, those demonstrating favorable robotics outcomes had a higher number of conflicted authors and a higher mean industry payment per author. There was no difference in the level of evidence or journal impact factor.DiscussionNearly all studies comparing robotic THA, TKA, and UKA to conventional techniques involve financially conflicted authors. Further studies without COI may provide unbiased results.     

Risk Factors and Effect of Acute Kidney Injury on Outcomes Following Total Hip and Knee Arthroplasty

BackgroundDevelopment of acute kidney injury (AKI) following primary total joint arthroplasty (TJA) is a potentially avoidable complication associated with negative outcomes including discharge to facilities and mortality. Few studies have identified modifiable risk factors or strategies that the surgeon may use to reduce this risk.MethodsWe identified all patients undergoing primary TJA at a single hospital from 2005 to 2017, and collected patient demographics, comorbidities, short-term outcomes, as well as perioperative laboratory results. We defined AKI as an increase in creatinine levels by 50% or 0.3 points. We compared demographics, comorbidities, and outcomes between patients who developed AKI and those who did not. Multivariate regressions identified the independent effect of AKI on outcomes. A stochastic gradient boosting model was constructed to predict AKI.ResultsIn total, 814 (3.9%) of 20,800 patients developed AKI. AKI independently increased length of stay by 0.26 days (95% confidence interval [CI] 0.14-0.38, P < .001), in-hospital complication risk (odds ratio = 1.73, 95% CI 1.45-2.07, P < .001), and discharge to facility risk (odds ratio = 1.26, 95% CI 1.05-1.53, P = .012). Forty-one predictive variables were included in the predictive model, with important potentially modifiable variables including body mass index, perioperative hemoglobin levels, surgery duration, and operative fluids administered. The final predictive model demonstrated excellent performance with a c-statistic of 0.967.ConclusionOur results confirm that AKI has adverse effects on outcome metrics including length of stay, discharge, and complications. Although many risk factors are nonmodifiable, maintaining adequate renal perfusion through optimizing preoperative hemoglobin, sufficient fluid resuscitation, and reducing blood loss, such as through the use of tranexamic acid, may aid in mitigating this risk.     

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development

BackgroundPancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood.MethodsThe fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models.ResultsEight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74).ConclusionSurgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.     

A mouse model of AChR deficiency syndrome with a phenotype reflecting the human condition

The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are generated by the substitution of the epsilon (adult) subunit for the gamma (fetal) subunit within the AChR pentamer. Null mutations of the adult AChR epsilon-subunit gene are the most common cause of the AChR deficiency syndrome. This is a disorder of neuromuscular transmission characterized by non-progressive fatigable muscle weakness present throughout life. In contrast with the human disorder, mice with AChR epsilon-subunit null mutations die between 10 and 14 weeks of age. We generated transgenic mice that constitutively express the human AChR gamma-subunit in an AChR epsilon-subunit 'knock-out' background. These mice, in which neuromuscular transmission is mediated by fetal AChR, live well into adult life but show striking similarities to human AChR deficiency syndrome. They display fatigable muscle weakness, reduced miniature endplate potentials and endplate potentials, reduced motor endplate AChR number and altered endplate morphology. Our results illustrate how species differences in the control of ion-channel gene expression may affect disease phenotype, demonstrate that expression of adult AChR subtype is not essential for long-term survival, and suggest that in patients with AChR deficiency syndrome, up-regulation of the gamma-subunit could be a beneficial therapeutic strategy.     

Synaptic organization of excitatory and inhibitory boutons associated with spinal neurons which project through the dorsal columns of the cat

The cell bodies and proximal dendrites of postsynaptic dorsal column neurons were examined for synaptic boutons which displayed immunoreactivity for the principal excitatory and inhibitory neurotransmitters, glutamate and GABA. The neurons were labelled by retrograde transport of horseradish peroxidase and GABA or glutamate-containing boutons were revealed by performing postembedding immunogold reactions on electron microscope sections. Five neurons were examined and all of them were postsynaptic to boutons which contained either GABA or glutamate. Quantitative analysis of two of the cells revealed that more than 90% of the synaptic profiles associated with them displayed immunogold reactions for these transmitters. Analysis of series of alternate sections, which were reacted for either GABA or glutamate, showed that there was no overlap in the populations of immunoreactive boutons. Furthermore, GABA and glutamate immunoreactions were associated with boutons which had different morphological characteristics. In addition, some large glutamate-enriched boutons were postsynaptic to small boutons which displayed immunogold reactions for GABA. This study demonstrates morphological bases for direct excitation, postsynaptic inhibition and presynaptic inhibition of postsynaptic dorsal column cells.     

Effectiveness of antipsychotic therapy in a naturalistic setting: a comparison between risperidone, perphenazine, and haloperidol

BACKGROUND: Therapeutic ineffectiveness and noncompliance with antipsychotic agents are major contributors to rehospitalization in patients with psychotic disorders. It is unknown whether risperidone's favorable side effect profile compared with that of the conventional antipsychotics results in improved compliance and reduced hospitalizations in a naturalistic setting. The purpose of this study was to test the hypothesis that treatment with risperidone reduces readmission rates and associated costs when compared with treatment with perphenazine or haloperidol. METHOD: Inpatients prescribed either risperidone, perphenazine, or haloperidol between January 1, 1995, and December 31, 1995, as a single oral antipsychotic at discharge were retrospectively identified. Data were collected for that index hospitalization and for a 1-year follow-up period. Primary outcome measures included re-admission rates, changes in antipsychotic therapy, anticholinergic drug use, and costs. RESULTS: There were 202 evaluable patients (81 treated with risperidone, 78 with perphenazine, and 43 with haloperidol). Baseline demographics were similar between groups except that more patients in the risperidone group had a primary diagnosis of psychotic disorder or had been hospitalized in the year prior to study. The percentage of patients readmitted during the 1-year follow-up period was similar among drug groups (41% risperidone, 26% perphenazine, and 35% haloperidol) when controlled for baseline differences in diagnosis and hospitalization history (p = .32). Anticholinergic drug use was more common in the haloperidol group (p = .004). Mean yearly cost (drug + hospitalization) in the risperidone group was $20,317, nearly double that in the other treatment groups (p < .001). CONCLUSION: The results from this naturalistic study indicate that the high cost of risperidone is not offset by a reduction in readmission rates when compared with conventional antipsychotics.     

Resuscitation of severe chest trauma with four different hemoglobin-based oxygen-carrying solutions

BACKGROUND: The purpose of this study was to test whether polynitroxylation (PN) improved the therapeutic profile of hemoglobin-based oxygen-carrying compounds (HBOCs) that were unpolymerized (alphaalphaHb) or 70% polymerized (polyHb) in a clinically relevant model that combines pulmonary injury and reperfusion. To our knowledge, four different HBOC formulations have never been compared in the same trauma model. METHODS: Anesthetized, ventilated swine (n = 45) received a unilateral lung contusion + 25% hemorrhage. After 60 minutes, 250 mL of either PNalphaalphaHb (n = 5), alphaalphaHb (n = 10), PNpolyHb (n = 6), polyHb (n = 5), or normal saline (NaCl, n = 10) was administered for 20 minutes, followed by standard crystalloid resuscitation for 30 minutes, and supplemental crystalloid as required for 6 hours to maintain heart rate <100 beats/min and mean arterial pressure >70 mm Hg. RESULTS: Nine of 45 deaths occurred before resuscitation. Survival time was 395 minutes with NaCl versus 303 minutes with alphaalphaHb (p = 0.03) or 238 minutes with PNalphaalphaHb (p = 0.04). With both polymerized HBOCs, survival was 480 minutes (polyHb vs. alphaalphaHb, p = 0.005; PNpolyHb vs. PNalphaalphaHb, p = 0.006). All HBOCs were pressors (all p < 0.05) and all reduced the supplemental fluid required to maintain systemic hemodynamics during resuscitation (all p < 0.05). By 90 minutes postresuscitation, cardiac index was 112% of baseline with NaCl (p < 0.02), but was 78% with alphaalphaHb (p = not significant), 63% with PNalphaalphaHb (p < 0.01), 79% with PNpolyHb (p < 0.01), and 67% with polyHb p < 0.02). Relative to NaCI, no HBOC altered trauma-induced neutrophilia, thrombocytopenia, or the trauma-induced increases in bronchoalveolar lavage protein or bronchoalveolar lavage neutrophils. CONCLUSION: After resuscitation from chest trauma, we observed the following: (1) all HBOCs reduced fluid requirements and increased right and left ventricular afterload versus NaCl, which further compromised an already marginal cardiac performance; (2) mortality was less with polyHbs relative to alphaalphaHb, but the pressor action was unchanged; (3) the pressor action was less with polynitroxylated compounds relative to the unmodified HBOC, but this chemical modification had no effect on mortality; and (4) the pressor action of HBOCs must be attenuated by strategies other than polymerization or polynitroxylation for these compounds to be safe, effective resuscitants in humans.