Citations

11 Background: Six months of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (CC) remains a standard in high-risk stage III patients. Early treatment discontinuation (ETD) could worsen the prognosis. In addition, there is current lack of data on the prognostic impact of early oxaliplatin only discontinuation (EOD). Methods: We studied the prognostic impact of ETD and EOD in patients with stage III CC who participated in 11 relevant clinical trials of the ACCENT and IDEA databases, where patients were planned to receive 6 months of adjuvant fluoropyrimidine plus oxaliplatin (FOLFOX or CAPOX). ETD was defined as discontinuation of treatment before 75% of cycles of chemotherapy. EOD was defined as discontinuation of oxaliplatin only, while continuing the fluoropyrimidine, before 75% of cycles of oxaliplatin. Association between ETD/EOD and overall survival (OS) and disease-free survival (DFS) was assessed by Cox model adjusted for prognostic factors. Results: ETD analysis included 10,444 patients (FOLFOX n = 7,033; CAPOX n = 3,411), with 20.9% of patients with ETD (17.8% with FOLFOX and 27.2% with CAPOX, p < 0.001). Out of 7,243 patients, 18.8% experienced EOD (17.4% FOLFOX versus 21.4% with CAPOX, p < 0.001). Compared to patients without ETD or EOD, patients with ETD or EOD were statistically more likely to be women, older, with higher ECOG-PS ≥ 1, and in addition for ETD, a Body Mass Index (BMI) < 18.5 kg/m2. In multivariate analyses, ETD was associated with a decrease in DFS and OS in the overall population (HR: 1.40 95%CI 1.23-1.58, p < 0.001 and HR: 1.51 95%CI 1.31-1.74, p < 0.001, respectively). The same pattern was present with FOLFOX and CAPOX regimen, and also in low-risk and high-risk groups for each regimen with the exception of the CAPOX regimen in the low-risk group for DFS and OS. By contrast, EOD was not associated with reduced DFS or OS in the overall population (HR: 1.10 95%CI 0.77-1.58, p = 0.6 and HR: 0.97 95%CI 0.62-1.52, p = 0.9, respectively), in the low-risk group (HR: 0.97 95%CI 0.56-1.66, p = 0.9 and HR: 0.97 95%CI 0.51-1.82, p = 0.9, respectively) and high-risk group (HR: 1.22 95%CI 0.74-2.02, p = 0.4 and HR: 1.05 95%CI 0.53-2.08, p = 0.9, respectively) and for all subgroups of regimen. Conclusions: In patients treated with 6 months of oxaliplatin-based adjuvant chemotherapy for stage III CC, ETD was associated with a decrease in DFS and OS. By contrast, EOD was not significantly associated with poorer outcomes. In case of relevant neurotoxicity during a 6 months schedule, these data are not in favor of continuing oxaliplatin beyond 75% of planned cycles of adjuvant chemotherapy, and demonstrate that fluoropyrimidines remain the cornerstone of adjuvant chemotherapy in localized CC.

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, clinical situations in which phage therapy might be considered, dosing, route of administration, and outcomes.

Abstract Recent advances in the science and technology of artificial intelligence (AI) and growing numbers of deployed AI systems in healthcare and other services have called attention to the need for ethical principles and governance. We define and provide a rationale for principles that should guide the commission, creation, implementation, maintenance, and retirement of AI systems as a foundation for governance throughout the lifecycle. Some principles are derived from the familiar requirements of practice and research in medicine and healthcare: beneficence, nonmaleficence, autonomy, and justice come first. A set of principles follow from the creation and engineering of AI systems: explainability of the technology in plain terms; interpretability, that is, plausible reasoning for decisions; fairness and absence of bias; dependability, including “safe failure”; provision of an audit trail for decisions; and active management of the knowledge base to remain up to date and sensitive to any changes in the environment. In organizational terms, the principles require benevolence—aiming to do good through the use of AI; transparency, ensuring that all assumptions and potential conflicts of interest are declared; and accountability, including active oversight of AI systems and management of any risks that may arise. Particular attention is drawn to the case of vulnerable populations, where extreme care must be exercised. Finally, the principles emphasize the need for user education at all levels of engagement with AI and for continuing research into AI and its biomedical and healthcare applications.

Abstract Background Previous prospective studies highlighted dairy intake as a risk factor for Parkinson's disease (PD), particularly in men. It is unclear whether this association is causal or explained by reverse causation or confounding. Objective The aim is to examine the association between genetically predicted dairy intake and PD using two‐sample Mendelian randomization (MR). Methods We genotyped a well‐established instrumental variable for dairy intake located in the lactase gene (rs4988235) within the Courage‐PD consortium (23 studies; 9823 patients and 8376 controls of European ancestry). Results Based on a dominant model, there was an association between genetic predisposition toward higher dairy intake and PD (odds ratio [OR] per one serving per day = 1.70, 95% confidence interval = 1.12–2.60, P = 0.013) that was restricted to men (OR = 2.50 [1.37–4.56], P = 0.003; P ‐difference with women = 0.029). Conclusions Using MR, our findings provide further support for a causal relationship between dairy intake and higher PD risk, not biased by confounding or reverse causation. Further studies are needed to elucidate the underlying mechanisms. © 2022 International Parkinson and Movement Disorder Society

AbstractBackgroundMale hypogonadism (testosterone level < 300 ng/dl) is a clinical syndrome that results from failure of the testis to produce physiological levels of testosterone. Most marketed testosterone replacement therapy products often require multiple dose adjustment clinic visits to achieve the desired, eugonadal testosterone levels.ObjectiveTo evaluate the efficacy and safety of a novel oral testosterone undecanoate therapy for the treatment of hypogonadism.Material and methodsNinety‐five (N = 95) hypogonadal men were enrolled in this open‐label, single‐arm, multicenter study in the United States (NCT03242590). Subjects received 225 mg of oral testosterone undecanoate (TLANDO) twice a day for 24 days without dose adjustment. Primary efficacy was percentages of subjects who achieved mean 24‐h testosterone levels within the eugonadal range and secondary efficacies were evaluated based on the upper limit of lab normal range of testosterone concentration.ResultsSubjects enrolled were on average age of 56 years, with about 17% of subjects older than 65 years. The mean body mass index was 32.8 kg/m2. The baseline mean total testosterone values were below the normal range (202 ± 74 ng/dl). Post‐treatment with 450 mg testosterone undecanoate daily dose without dose adjustment, 80% of subjects (95% confidence interval of 72%–88%) achieved a testosterone Cavg in the normal range and restored testosterone levels to mean testosterone Cavg of 476 ± 184 ng/dl at steady state. Testosterone restoration was comparable to other approved testosterone replacement therapy products. TLANDO was well tolerated with no deaths, no drug‐related serious adverse events, and no hepatic adverse events.Discussion and conclusionsTLANDO restored testosterone levels to the normal range in the majority of hypogonadal males. This new oral testosterone replacement therapy can provide an option for no‐titration oral testosterone replacement therapy. This therapy has the potential to improve patient compliance in testosterone replacement therapy.

Abstract Background: Lung-protective ventilation is often used in critically ill patients with acute respiratory failure, including those without acute respiratory distress syndrome. While disparities exist in the delivery of critical care based on gender, race, and insurance status, it is unknown whether there are disparities in the use of lung-protective ventilation. The objective of our study was to determine whether gender-, racial / ethnic-, or insurance status-based disparities exist in the use of lung-protective ventilation for critically ill mechanically ventilated patients in the United States (U.S.).Methods: This was a secondary data analysis of the U.S. Critical Illness and Injury Trials Group Critical Illness Outcomes Study, a prospective multi-center cohort study conducted from 2010 - 2012. The dependent variable of interest was the proportion of patients receiving tidal volume > 8 mL/kg predicted body weight (PBW). The independent variables of interest were gender, insurance status, and race / ethnicity. Results: Our primary analysis included 1,595 mechanically ventilated patients from 59 intensive care units (ICUs) in the U.S. Women were more likely to receive tidal volumes > 8 ml/kg PBW than men (odds ratio [OR] = 3.25, 95% confidence interval [CI] = 2.58 – 4.09), though this relationship was substantially weakened after adjusting for gender differences in height (OR = 1.26 95% CI = 0.94 – 1.71). The underinsured were significantly more likely to receive tidal volume > 8 ml/kg PBW than the insured in multivariable analysis (odds ratio = 1.54, 95% confidence interval = 1.16 – 2.04). The prescription of > 8 ml/kg PBW tidal volume did not differ by racial or ethnic categories. Conclusions: In this prospective nationwide cohort of critically ill mechanically ventilated patients, women and the underinsured were less likely than their comparators to receive lung protective ventilation, with no apparent differences based on race / ethnicity alone. Differences in height between men and women do not fully explain this disparity. Future research should evaluate whether implicit bias affects tidal volume choice and other management decisions in critical care.

Introduction This study was designed to assess current recommendations from child neurologists and epileptologists on masking for school-age children with epilepsy. Methods A 7-item survey was created and sent out to members of the Child Neurology Society and Pediatric Epilepsy Research Consortium in August of 2021 to assess current practice and provider recommendations on masking. Results One hundred four individuals participated with representation from all regions of the United States. Masking was recommended by 95.1%, with 63.4% (n = 66) noting exception of those with severe intellectual disability, autism, and behavioral problems. Of those who write exemption letters, 54% write these <5% of the time. Only 3% reported potential adverse events associated with masking. Conclusion Nearly all respondents recommended masking for school-age children with epilepsy. Potential risks of masking and adverse events were low. Improved guidance on masking is needed to ensure academic success of our patients with epilepsy.

OBJECTIVE Spine robots have seen increased utilization over the past half decade with the introduction of multiple new systems. Market research expects this expansion to continue over the next half decade at an annual rate of 20%. However, because of the novelty of these devices, there is limited literature on their learning curves and how they should be integrated into residency curricula. With the present review, the authors aimed to address these two points. METHODS A systematic review of the published English-language literature on PubMed, Ovid, Scopus, and Web of Science was conducted to identify studies describing the learning curve in spine robotics. Included articles described clinical results in patients using one of the following endpoints: operative time, screw placement time, fluoroscopy usage, and instrumentation accuracy. Systems examined included the Mazor series, the ExcelsiusGPS, and the TiRobot. Learning curves were reported in a qualitative synthesis, given as the mean improvement in the endpoint per case performed or screw placed where possible. All studies were level IV case series with a high risk of reporting bias. RESULTS Of 1579 unique articles, 97 underwent full-text review and 21 met the inclusion and exclusion criteria; 62 articles were excluded for not presenting primary data for one of the above-described endpoints. Of the 21 articles, 18 noted the presence of a learning curve in spine robots, which ranged from 3 to 30 cases or 15 to 62 screws. Only 12 articles performed regressions of one of the endpoints (most commonly operative time) as a function of screws placed or cases performed. Among these, increasing experience was associated with a 0.24- to 4.6-minute decrease in operative time per case performed. All but one series described the experience of attending surgeons, not residents. CONCLUSIONS Most studies of learning curves with spine robots have found them to be present, with the most common threshold being 20 to 30 cases performed. Unfortunately, all available evidence is level IV data, limited to case series. Given the ability of residency to allow trainees to safely perform these cases under the supervision of experienced senior surgeons, it is argued that a curriculum should be developed for senior-level residents specializing in spine comprising a minimum of 30 performed cases.

OBJECTIVE With the expanding indications for and increasing popularity of minimally invasive surgery (MIS) for lumbar spinal fusion, large-scale outcomes analysis to compare MIS approaches with open procedures is warranted. METHODS The authors queried the Quality Outcomes Database for patients who underwent elective lumbar fusion for degenerative spine disease. They performed optimal matching, at a 1:2 ratio between patients who underwent MIS and those who underwent open lumbar fusion, to create two highly homogeneous groups in terms of 33 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, indications, and operative details). The outcomes of interest were overall satisfaction, decrease in Oswestry Disability Index (ODI), and back and leg pain, as well as hospital length of stay (LOS), operative time, reoperations, and incidental durotomy rate. Satisfaction was defined as a score of 1 or 2 on the North American Spine Society scale. Minimal clinically important difference (MCID) in ODI was defined as ≥ 30% decrease from baseline. Outcomes were assessed at the 3- and 12-month follow-up evaluations. RESULTS After the groups were matched, the MIS and open groups consisted of 1483 and 2966 patients, respectively. Patients who underwent MIS fusion had higher odds of satisfaction at 3 months (OR 1.4, p = 0.004); no difference was demonstrated at 12 months (OR 1.04, p = 0.67). Lumbar stenosis, single-level fusion, higher American Society of Anesthesiologists Physical Status Classification System grade, and absence of spondylolisthesis were most prominently associated with higher odds of satisfaction with MIS compared with open surgery. Patients in the MIS group had slightly lower ODI scores at 3 months (mean difference 1.61, p = 0.006; MCID OR 1.14, p = 0.0495) and 12 months (mean difference 2.35, p < 0.001; MCID OR 1.29, p < 0.001). MIS was also associated with a greater decrease in leg and back pain at both follow-up time points. The two groups did not differ in operative time and incidental durotomy rate; however, LOS was shorter for the MIS group. Revision surgery at 12 months was less likely for patients who underwent MIS (4.1% vs 5.6%, p = 0.032). CONCLUSIONS In patients who underwent lumbar fusion for degenerative spinal disease, MIS was associated with higher odds of satisfaction at 3 months postoperatively. No difference was demonstrated at the 12-month follow-up. MIS maintained a small, yet consistent, superiority in decreasing ODI and back and leg pain, and MIS was associated with a lower reoperation rate.