Citations

Importance Bioenergetic failure has been proposed as a driver of amyotrophic lateral sclerosis (ALS). CNM-Au8 is a suspension of gold nanocrystals that catalyzes the conversion of nicotinamide adenine dinucleotide hydride into NAD + , resulting in an increase of cellular adenosine triphosphate production. Objective To determine the effects of CNM-Au8 on ALS disease progression. Design, Setting, and Participants CNM-Au8 was tested as a regimen of the HEALEY ALS Platform Trial, a phase 2/3, multicenter, randomized, double-blind platform trial. The study was conducted at 54 sites in the US from July 2020 to March 2022 (final follow-up, March 17, 2022). A total of 161 participants with ALS were randomized to receive CNM-Au8 (n = 120) or regimen-specific placebo (n = 41). Data from 123 concurrently randomized placebo participants in other regimens were combined for analyses. Interventions Eligible participants were randomized in a 3:3:2 ratio to receive CNM-Au8 60 mg daily (n = 61), CNM-Au8 30 mg daily (n = 59), or matching placebo (n = 41) for 24 weeks. Main Outcomes and Measures The primary efficacy outcome was change from baseline through week 24 in ALS disease severity measured by a bayesian shared parameter model of function (based on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) and survival, which provided an estimate of the rate of disease progression measured by the disease rate ratio (DRR), with a DRR of less than 1 indicating treatment benefit. Secondary end points included a Combined Assessment of Function and Survival using a joint-rank test, rate of decline in slow vital capacity (percent predicted), and survival free of permanent assisted ventilation. Results Among 161 participants who were randomized within the CNM-Au8 regimen (mean age, 58.4 years; 61 [37.9%] female), 145 (90%) completed the trial. In the primary analysis comparing the combined CNM-Au8 dosage groups vs the combined placebo groups, the primary end point (DRR, 0.97 [95% credible interval, 0.783-1.175]; posterior probability of DRR <1, 0.65) and the 3 secondary end points suggested no benefit or harm of CNM-Au8. In the active (n = 120) vs placebo (n = 163) groups, the most common adverse events were diarrhea (23 [19%] vs 12 [7%]), nausea (17 [14.2%] vs 14 [8.6%]), fatigue (12 [10.8%] vs 30 [18.4%]), and muscular weakness (24 [20%] vs 45 [27.6%]). Conclusions and Relevance No benefit of CNM-Au8 on ALS disease progression was observed at 24 weeks. Trial Registration ClinicalTrials.gov Identifiers: NCT04297683 , NCT04414345

Abstract Severe aortic valve regurgitation, if not timely treated, can significantly impact patients’ survival both for tricuspid aortic valve and bicuspid aortic valve patients, with the latter being significantly younger. Increased understanding of the root anatomy and its physiology has opened the way to techniques of aortic valve repair surgery. The techniques mainly relate to re-establishing a correct root and annular geometry and eliminating leaflet prolapse. These techniques are applied both in the presence of a dilated and normal root and are equally valid for tricuspid or bicuspid valve. Techniques for repairing a bicuspid valve might vary depending on the different valve phenotypes. Medium and long-term results appear favourable and potentially superior to those of prosthetic replacement in terms of valve-related complications and quality of life. Optimal surgical treatment, especially in younger and selected patients, should aim to avoid aortic valve replacement and its related complications.

OBJECTIVE Sepsis is associated with significant morbidity and mortality in pediatric hematology, oncology, and transplant (PHOT) patients. This study characterized PHOT patients who developed hospital-onset sepsis more than 12 hours after admission and identified risk factors for 30-day sepsis-attributable (SA) mortality. PATIENTS AND METHODS We analyzed an existing multicenter database of sepsis collected prospectively over 5 years (2017–2021) as part of the Improving Pediatric Sepsis Outcomes Collaborative. Sepsis was defined using operational elements documented in the health records based on International Classification of Diseases, Tenth Revision codes, treatment, diagnostic tests, and sepsis screen, huddle, or order set use. RESULTS A total of 9604 sepsis episodes in PHOT patients from 49 hospitals were analyzed: 70.5% were identified in the emergency department (ED), 10.9% in inpatient settings less than or equal to 12 hours from admission, and 18.6% were hospital onset. Only 52.5% of patients with hospital-onset sepsis were identified using a sepsis recognition method compared with 87.2% in the ED (P < .001). The overall 30-day SA mortality was 2.2%, with a higher rate (6.9%) among those with hospital-onset sepsis compared with those who developed sepsis at presentation or less than or equal to 12 hours (1.1%, P < .001). CONCLUSIONS Although the difference in SA mortality between hospitalized and nonhospitalized patients may be impacted by nonmeasurable confounders inherent to the type of patients presenting in the different care settings, we reported system-based improvements that may reduce mortality. The 30-day SA mortality was lower in hospitalized PHOT patients when sepsis was detected by early recognition methods, supporting the need for efforts to implement sepsis recognition tools in the inpatient setting.

ABSTRACTIntroductionLung transplantation has been evolving since its inception in 1963. Over recent years, literature has suggested a shift in the perioperative strategy of mechanical support toward extracorporeal membrane oxygenation (ECMO) as the preferred modality of extracorporeal life support (ECLS) in lung transplantation. The Survey of ECLS Application in Lung transplantation (SEAL) was designed to elucidate the current practice patterns of perioperative ECLS within the United States.MethodsIn this cross‐sectional study, a physician from 62 adult lung transplantation centers across the United States of America (USA) was surveyed on their institutional practices regarding the perioperative management of lung transplantation patients, with a focus on mechanical support.ResultsThe survey completion rate was 74% (46/62 eligible institutions). Most transplant centers utilize venoarterial (VA) ECMO (78%, 36/46) and/or venovenous (VV) ECMO (93%, 29/43) as a bridge to lung transplantation. When ECLS is used intraoperatively, 61% of (28/46) responding programs use VA ECMO as their preferred support. All programs use transesophageal echocardiography (TEE) intraoperatively, 85% (33/39) cannulate for ECMO centrally, and 74% (29/39) use a combination of inhaled and intravenous anesthesia while using ECMO intraoperatively. Most programs do not use antifibrinolytic during VA ECMO (62%, 28/45). Anticoagulation management and VA ECMO flows throughout the procedure showed considerable variation.ConclusionData from SEAL illustrates that though there are some practice commonalities within the United States, there is also quite a bit of variability in practice. Multiple dominant practices within the USA are consistent with a recently published International Society of Heart and Lung Transplantation consensus.

BACKGROUND: Increased specialty competitiveness, alongside the inception of virtual interviews, has increased the number of applications submitted to the Electronic Residency Application Service (ERAS) in anesthesiology. ERAS introduced signals to provide applicants with a means to demonstrate interest in a select group of residency programs. In the 2023 to 2024 application cycle, anesthesiology applicants had the opportunity to send 5 gold and 10 silver signals in a tiered system. METHODS: This multicenter, cross-sectional (exempt) research survey was created by members of the executive council of the Association of Anesthesiology Core Program Directors (AACPD) and housed and distributed through REDCap and the University of Nebraska Medical Center. Publicly available contact information of anesthesiology core program directors was obtained from the Accreditation Council for Graduate Medical Education (ACGME) website and membership roster of the AACPD. In total, 174 anesthesiology programs were identified. A survey invitation was distributed on March 12, 2024, to all programs via e-mail with reminders. The survey closed on April 30, 2024. Survey responses were collected anonymously, with instructions to provide 1 response per program. All statistical summaries and analyses were performed using SAS 9.3 (SAS Institute). RESULTS: The survey was sent to all 174 identified programs, with a response rate of 48.9%. Small programs were defined as having <44 residents, medium 44 to 62 residents, and large >62 residents. Small programs received significantly fewer applications (median 1255) than medium (1420) and large (1558) programs ( P = .0005). There was a statistically significant difference in the number of gold signals received based on program size, with large programs receiving significantly more than medium (169 vs 116, P = .0238) or small programs (168 vs 71, P < .0001). Applicants sending gold signals were more likely to receive an interview compared to those who sent silver signals (56.7% vs 31%, P ≤ .0001). Of the those interviewed, applicants who sent gold signals comprised 42% (28.7%–52.6%), whereas applicants who sent silver signals comprised 45.5% (33%–54.7%). Applicants who did not send a program signal but signaled geographically made up a smaller portion of the interview group at 3% (0%–15.4%). The percentage of matched residents sending gold signals made up 66.7% (47.1%–82.4%) of a program’s match list, whereas those sending silver signals were 25% (11.1%–33.3%) of the matched cohort. CONCLUSIONS: Anesthesiology applicants who sent program signals were selected for a large majority of available interview positions, and interviewed applicants who submitted gold and silver signals comprised the vast majority of matched resident cohorts.

ABSTRACT Rituximab, gemcitabine, and oxaliplatin (R‐GemOx) is a commonly used chemoimmunotherapy regimen for relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), but there are limited real‐world data. In a multicenter retrospective study from a cohort of eight US academic centers (LEO CReWE), we evaluated 183 patients with R/R DLBCL and high‐grade B cell lymphoma treated with R‐GemOx, including subgroups treated without intent for consolidation with autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T cell therapy ( n = 100), those utilizing R‐GemOx as a bridge to ASCT or CAR T ( n = 83), and those aged 70 and older ( n = 71). Overall response rates (ORRs) for all patients treated with R‐GemOx were 45% with a complete response (CR) rate of 29%. The median event‐free survival (EFS) was 2.3 months, and the median overall survival (OS) was 13.5 months. Patients receiving R‐GemOx without intent for ASCT or CAR T had ORR and CR rates of 33% and 18%, respectively, with median EFS and OS of 2.0 and 9.5 months, respectively. Patients receiving R‐GemOx as a bridge to ASCT or CAR T had ORR and CR rates of 57% and 36%, respectively, with median EFS and OS of 3.5 and 17.4 months, respectively. Patients receiving R‐GemOx aged 70 and older had ORR and CR rates of 53% and 33%, respectively, with median EFS and OS of 2.2 and 13.9 months, respectively. These data provide a benchmark for R‐GemOx in the rapidly evolving landscape of R/R DLBCL therapies.

Objective(s): To quantify and compare pre-procedure worry versus the experience of pain, gagging, and dyspnea during in-office laryngoscopy procedures in patients who did or did not receive pre-procedure anxiolytics, and to explore patient perception of intra-procedure interventions. Methods: Patients undergoing awake laryngology procedures at a quaternary care center were enrolled. The State-Trait Anxiety Inventory (STAI) Y1 and Y2 questionnaires were administered to establish baseline levels of state anxiety and trait anxiety, respectively. Pre-procedure and post-procedure surveys assessed patient perception of select interventions. Results: 34 patients were enrolled (35.3% female, 91.2% white, mean age 60 years). Pre-procedure, 51.5% of patients reported some degree of worry about pain, 61.8% about gagging, 52.9% about dyspnea, and 55.9% about having something in their nose/throat. Post-procedure, 54.5% reported experiencing pain to some degree, 63.6% had gagging, 39.4% had dyspnea, and 78.7% were bothered by having something in their nose/throat. Patients who received a pre-procedure anxiolytic were significantly more likely to report more pain compared to those who did not. The highest rated interventions were pre-procedural education (97.0% “Very helpful”), verbal reassurance (96.9%), provider communicating steps of the procedure (96.9%), and reminders to breathe (87.5%). Conclusion: For patients undergoing awake laryngology procedures, the anticipation of gagging, pain, trouble breathing, and scope-related discomfort are worrisome factors. Of these, scope-related discomfort and gagging are the most often-reported sources of intraprocedural discomfort. The interventions patients found most helpful were based on preprocedural education and clear intraprocedural communication, which suggests that purposeful communication has a role in relieving anxiety. Level of evidence: Level 4

Abstract Background: Prostate artery embolization (PAE) requires a careful understanding of pelvic arterial anatomy and identifying prostatic artery variants. Pre-procedure CTA and intra-procedural cone beam CT are traditional means of planning and performing PAE, with the latter providing guidance for embolization. Photon counting detector (PCD) CT is a novel technology enabling ultra-high spatial resolution (UHR) whole-body imaging, with reconstructed slices as thin as 200 um. For PAE, we obtain a single UHR PCD CT acquisition, which provides both detailed pre-procedure pelvic arterial anatomy information and a registration reference for intra-procedural embolization guidance. Case Presentation: In five patients who underwent technically successful PAE via a left transradial approach, the pre-procedure diagnostic UHR PCD prostate CTA delineated bilateral prostatic artery origins and course in all cases, as confirmed with conventional angiograms. Further, registration of the UHR PCD CT for embolization guidance was successful in all cases, augmenting vessel selection. No complication occurred. Conclusion: UHR PCD CT is a novel acquisition option that is well suited to PAE due to its ability to delineate small vessels. Further, our experience has shown that a single pre-procedure scan can also be utilized for intra-procedural embolization guidance, obviating the need for a traditional cone beam CT angiogram. Further research is needed to assess reductions in radiation dose, contrast use, and intra-procedural time with these techniques.

Background and Objectives: Robotic-assisted laparoscopy (RS) has been widely adopted for the management of endometrial cancer (EC) due to favorable perioperative outcomes, especially in the context of obesity, which is an established risk factor for EC. This study retrospectively evaluated the perioperative outcomes of RS versus conventional laparoscopy (LS) in treating EC and atypical endometrial hyperplasia (AH). Methods: Between November 2021 and October 2023, 138 patients with AH or EC underwent surgery at the Clinic of Obstetric and Gynecological—Azienda Sanitaria Universitaria Friuli Centrale, Udine. All patients had total hysterectomy with bilateral salpingo-oophorectomy, with or without lymphadenectomy or sentinel lymph node biopsy. The study included 62 patients treated with LS and 62 with RS. Results: The median BMI was higher in the RS group (35.5 vs. 24 kg/m2, p = 0.001). There was no significant difference in operative time between the laparoscopic group and the robotic console time (median 130 vs. 130 min, p = 0.131). No significant differences were found in terms of blood loss, conversion to laparotomy, intraoperative complications, hospital stay, or early postoperative complications between the two groups. Conclusions: Our data confirm the feasibility of robotic surgery in obese patients, allowing surgical results comparable to those of laparoscopy in normal-weight patients.

Abstract Objective Dravet syndrome is a developmental and epileptic encephalopathy characterized by drug‐resistance, lifelong seizures, and significant comorbidities including intellectual and motor impairment. Receiving a diagnosis of Dravet syndrome is challenging for parents/caregivers, and little research has focused on how the diagnosis should be given. A Delphi consensus process was undertaken to determine key aspects for healthcare professionals (HCPs) to consider when communicating a Dravet syndrome diagnosis to parents/caregivers. Methods Following a literature search and steering committee review, 34 statements relating to the first diagnosis consultation were independent‐ and anonymously voted on (from 1, totally inappropriate, to 9, totally appropriate) by an international group of expert child neurologists, neuropsychiatrists, nurses, and patient advisory group (PAG) representatives. The statements were divided into five chapters: (i) communication during the first diagnosis consultation, (ii) information to be delivered during the first diagnosis consultation, (iii) points to be reiterated at the end of the first diagnosis consultation, (iv) information to be delivered at subsequent consultations, and (v) communication around genetic testing. Statements receiving ≥ 75% of the votes with a score of ≥7 and/or with a median score of ≥8 were considered consensual. Results The statements were evaluated by 44 HCPs and PAG representatives in the first round of voting; 29 statements obtained strong consensus, 3 received good consensus, and 2 did not reach consensus. The committee reformulated and resubmitted 4 statements for evaluation (42/44 voters): 3 obtained strong consensus and 1 remained not consensual. The final consensual recommendations include guidance on consultation setting, key disease aspects to convey, how to discuss genetic testing results, disease evolution, and the risk of SUDEP, among other topics. Significance It is hoped that this international Delphi consensus will facilitate a better‐structured initial diagnosis consultation and offer further support for parents/caregivers at this challenging time of learning about Dravet syndrome. Plain Language Summary Diagnosis of Dravet syndrome, a rare and severe form of childhood‐onset epilepsy, is often challenging to give to parents. This international study developed guidance and recommendations to help healthcare professionals better structure and personalize this disclosure. By following this advice, doctors can provide more tailored support to families, improving their understanding and management of the condition.