Citations

Background Multiple myeloma is a cancer of plasma cells that often leads to complications including osteolytic bone lesions, nephropathy and neuropathy. Multiple myeloma is only one etiology of many cancer pain conditions that may necessitate interventional pain treatment when refractory to multimodal medications. Notably, local anesthetic systemic toxicity is a rare but life-threatening complication of local anesthetic administered for these interventions. Case presentation A 50–60-year-old woman presented with multiple myeloma complicated by chronic bone pain and in an acute pain crisis. A fluoroscopic-guided L4–5 epidural catheter was placed with clinical doses of bupivacaine for comfort to undergo MRI of the spine. Soon after, she became tachycardic, tachypneic and hypoxic requiring non-invasive positive pressure airway support. As this respiratory distress was attributed to a large pleural effusion, a pigtail catheter was inserted in the intensive care unit with submaximally dosed lidocaine infiltration. She then developed a left bundle branch block followed by cardiovascular collapse minimally responsive to high-dose inotrope and vasopressor support. Lipid emulsion was started with dramatic therapeutic response and recovery to baseline. A CT of the thoracolumbar spine showed worsening extensive lytic lesions throughout all vertebral bodies and ribs from diffuse myeloma. Conclusions Patients with oncologic lesions focal to the thoracolumbar spine may be at higher risk for local anesthetic systemic toxicity from palliative epidurals due to increased cancer-related angiogenesis. Likewise, local anesthetic infiltration for procedures near any malignant sites could have a similar risk and may require lower initial fractionated dosages with increased vigilance.

Abstract Background: Young doctors have made up a substantial part of healthcare forces during the Coronavirus Disease 2019 (COVID-19) pandemic. The aim of this study was to determine the rate and level of psychological distress among young doctors during the COVID-19 outbreak. Methods: This cross-sectional cohort study, dedicated to doctors, at or below the age of 40, was conducted in 62 countries as an online survey between September – November 2020. Survey questions covered the following areas: 1. demographics 2. work environment 3.the ‘Hospital Anxiety and Depression Scale (HADS)’ and the ‘Perceived Stress Scale 10 (PSS-10)’. The primary outcome was the rate and level of anxiety/depression and stress among surveyed population defined according to adopted cut off values (HADS>13, PSS-10>14). Secondary outcomes included risk factors for increased HADS and PSS-10 scores.Results: Among 1186 respondents, median aged 32 [29–36], 675 (44.5%) females, 96% reported a high level of anxiety/depression and 97% reported a high level of stress. Factors associated with significantly higher scores for anxiety/depression were increased work hours [OR 1.61 95%CI (1.12–2.34);p=0.01] and loss of pay [OR 5.53, 95% CI (1.57–19.47);p=0.008], while reduced work hours [OR 0.68 95% CI (0.48 - 0.98);p=0.03], increased salaries [OR 0.54 95% CI (0.35–0.85);p=0.003) and good training [OR 0.99 95%CI (0.99– 1.00);p=0.002] were associated with lower scores. Higher scores for stress were associated with higher professional experience [OR 1.08 95% CI (1.02–1.14);p=0.008], reduced salaries [OR 1.74 95% CI (1.01–2.92);p=0.04] and living with a partner [OR 1.53 95% CI (1.08–2.17);p=0.01]. Conclusions: A high rate of young doctors working clinically during the COVID-19 pandemic reported a persistently high level of psychological distress more than six months after the initial outbreak. Improvements in work organization, including reduced work hours and financial security are essential to prevent further psychological suffering among young doctors worldwide.

AbstractThere is a paucity of data to guide anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) with brain sensing. The clinical Medtronic Percept DBS device provides constrained brain sensing power within a frequency band (power‐in‐band [PIB]), recorded in 10‐min averaged increments. Here, four patients with temporal lobe epilepsy were implanted with an investigational device providing full bandwidth chronic intracranial electroencephalogram (cEEG) from bilateral ANT and hippocampus (Hc). ANT PIB‐based seizure detection was assessed. Detection parameters were cEEG PIB center frequency, bandwidth, and epoch duration. Performance was evaluated against epileptologist‐confirmed Hc seizures, and assessed by area under the precision‐recall curve (PR‐AUC). Data included 99 days of cEEG, and 20, 278, 3, and 18 Hc seizures for Subjects 1–4. The best detector had 7‐Hz center frequency, 5‐Hz band width, and 10‐s epoch duration (group PR‐AUC = .90), with 75% sensitivity and .38 false alarms per day for Subject 1, and 100% and .0 for Subjects 3 and 4. Hc seizures in Subject 2 did not propagate to ANT. The relative change of ANT PIB was maximal ipsilateral to seizure onset for all detected seizures. Chronic ANT and Hc recordings provide direct guidance for ANT DBS with brain sensing.

Abstract E1912 was a randomized phase 3 trial comparing indefinite ibrutinib plus 6 cycles of rituximab (IR) to 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) in untreated younger patients with CLL. We describe measurable residual disease (MRD) levels in E1912 over time and correlate them with clinical outcome. Undetectable MRD rates (<1 CLL cell per 104 leukocytes) were 29.1%, 30.3%, 23.4%, and 8.6% at 3, 12, 24, and 36 months for FCR, and significantly lower at 7.9%, 4.2%, and 3.7% at 12, 24, and 36 months for IR, respectively. Undetectable MRD at 3, 12, 24, and 36 months was associated with longer progression-free survival (PFS) in the FCR arm, with hazard ratios (MRD detectable/MRD undetectable) of 4.29 (95% confidence interval [CI], 1.89-9.71), 3.91 (95% CI, 1.39-11.03), 14.12 (95% CI, 1.78-111.73), and not estimable (no events among those with undetectable MRD), respectively. In the IR arm, patients with detectable MRD did not have significantly worse PFS compared with those in whom MRD was undetectable; however, PFS was longer in those with MRD levels <10−1 than in those with MRD levels above this threshold. Our observations provide additional support for the use of MRD as a surrogate end point for PFS in patients receiving FCR. In patients on indefinite ibrutinib-based therapy, PFS did not differ significantly by undetectable MRD status, whereas those with MRD <10−1 tended to have longer PFS, although continuation of ibrutinib would very likely be necessary to maintain treatment efficacy.

Abstract Background Graduate Medical Education training programs transitioned to all-virtual recruitment in 2020. Limited data have been published regarding the consequences of this transition. We aimed to understand (1) infectious diseases (ID) fellowship programs’ recruitment efforts and the effect of virtual recruitment on application and interview numbers and (2) the number of programs to which matched applicants applied and interviewed and applicants’ perspectives on virtual recruitment. Methods In 2020–2021, we surveyed all US ID fellowship program directors (PDs) and matched applicants. Descriptive data analysis was performed on quantitative survey items. Free-text responses were analyzed through a quantitative content analysis approach. Results The PD response rate was 68/158 (43%); the applicant response rate was at least 23% (85/365). PDs reported a 27% increase in mean number of applications received and a 45% increase in mean number of applicants interviewed compared with the previous year. Applicants especially valued the online program structure information, PD program overview videos, didactic and curriculum content, and fellow testimonials and profiles. Most applicants preferred interviews lasting no more than 40 minutes and interview days lasting no more than 5 hours. Nearly all (60/64, 94%) PDs adequately learned about candidates; most (48/64, 75%) felt unable to showcase their program as well as when in-person. Most PDs (54/64, 84%) and applicants (56/73, 77%) want an option for virtual recruitment. Conclusions Virtual recruitment enabled programs to accommodate more applicants and highlighted applicants’ preferences for programs’ augmented online presences and time-limited interview days. Most programs and applicants want an option for virtual interviews.

AbstractObjectivesThe Evolut R FORWARD study confirmed safety and effectivenesss of the Evolut R THV in routine clinical practice out to 1 year. Herein, we report the final 3‐year clinical follow up of the FORWARD study.BackgroundTranscatheter aortic valve replacement (TAVR) is a proven alternative to surgery in elderly patients with symptomatic severe aortic stenosis. Long‐term clinical outcome data with the Evolut R platform are scarce.MethodsFORWARD is a prospective multicenter observational study that evaluated the Evolut R system in routine clinical practice at 53 centres. Eligible patients had symptomatic native aortic valve stenosis or failed surgical aortic bioprosthesis and elevated operative risk per Heart‐Team assessment. TAVR was attempted in 1039 patients.ResultsMean age was 81.8 ± 6.2 years, 64.9% were women, STS score was 5.5 ± 4.5% and 34.2% were frail. Rates of all‐cause mortality and disabling stroke were 24.8% and 4.8% at 3 years. Early need for a new pacemaker implantation after TAVR (all‐cause mortality: with new PPI; 21.0% vs. without; 22.8%, p = 0.55) and the presence of > trace paravalvular regurgitation (all‐cause mortality: no or trace; 22.0% vs. ≥ mild; 25.5%, p = 0.29) did not affect survival. Between 1 and 3 years incidence rates of valve related intervention, endocarditis and clinically relevant valve thrombosis were low.ConclusionsThe Evolut R valve maintained a favorable safety profile through 3 years in routine clinical practice. Rates of transcatheter heart valve‐related adverse events were low.

Nuclear accumulation of CHMP7 leads to multiple cellular pathologies that can be mitigated via CHMP7 ASOs in familial and sporadic ALS iPSNs.

AbstractThe development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.