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PURPOSE Outcomes for patients with newly diagnosed multiple myeloma (NDMM) are heterogenous, with overall survival (OS) ranging from months to over 10 years. METHODS To decipher and predict the molecular and clinical heterogeneity of NDMM, we assembled a series of 1,933 patients with available clinical, genomic, and therapeutic data. RESULTS Leveraging a comprehensive catalog of genomic drivers, we identified 12 groups, expanding on previous gene expression–based molecular classifications. To build a model predicting individualized risk in NDMM (IRMMa), we integrated clinical, genomic, and treatment variables. To correct for time-dependent variables, including high-dose melphalan followed by autologous stem-cell transplantation (HDM-ASCT), and maintenance therapy, a multi-state model was designed. The IRMMa model accuracy was significantly higher than all comparator prognostic models, with a c-index for OS of 0.726, compared with International Staging System (ISS; 0.61), revised-ISS (0.572), and R2-ISS (0.625). Integral to model accuracy was 20 genomic features, including 1q21 gain/amp, del 1p, TP53 loss, NSD2 translocations, APOBEC mutational signatures, and copy-number signatures (reflecting the complex structural variant chromothripsis). IRMMa accuracy and superiority compared with other prognostic models were validated on 256 patients enrolled in the GMMG-HD6 (ClinicalTrials.gov identifier: NCT02495922 ) clinical trial. Individualized patient risks were significantly affected across the 12 genomic groups by different treatment strategies (ie, treatment variance), which was used to identify patients for whom HDM-ASCT is particularly effective versus patients for whom the impact is limited. CONCLUSION Integrating clinical, demographic, genomic, and therapeutic data, to our knowledge, we have developed the first individualized risk-prediction model enabling personally tailored therapeutic decisions for patients with NDMM.

Abstract The Infectious Diseases Society of America Training Program Directors Committee met in October 2022 and discussed an observed increase in clinical volume and acuity on infectious diseases (ID) services, and its impact on fellow education. Committee members sought to develop specific goals and strategies related to improving training program culture, preserving quality education on inpatient consult services and in the clinic, and negotiating change at the annual IDWeek Training Program Director meeting. This paper outlines a presentation of ideas brought forth at the meeting and is meant to serve as a reference document for infectious diseases training program directors seeking guidance in this area.

Background: Pedicle subtraction osteotomy (PSO) is a powerful tool for sagittal plane correction in patients with rigid adult spinal deformity (ASD); however, it is associated with high intraoperative blood loss and the increased risk of durotomy. The objective of the present study was to identify intraoperative techniques and baseline patient factors capable of predicting intraoperative durotomy. Methods: A tri-institutional database was retrospectively queried for all patients who underwent PSO for ASD. Data on baseline comorbidities, surgical history, surgeon characteristics and intraoperative maneuvers were gathered. PSO aggressiveness was defined as conventional (Schwab 3 PSO) or an extended PSO (Schwab type 4). The primary outcome of the study was the occurrence of durotomy intraoperatively. Univariable analyses were performed with Mann–Whitney U tests, Chi-squared analyses, and Fisher’s exact tests. Statistical significance was defined by p < 0.05. Results: One hundred and sixteen patients were identified (mean age 61.9 ± 12.6 yr; 44.8% male), of whom 51 (44.0%) experienced intraoperative durotomy. There were no significant differences in baseline comorbidities between those who did and did not experience durotomy, with the exception that baseline weight and body mass index were higher in patients who did not suffer durotomy. Prior surgery (OR 2.73; 95% CI [1.13, 6.58]; p = 0.03) and, more specifically, prior decompression at the PSO level (OR 4.23; 95% CI [1.92, 9.34]; p < 0.001) was predictive of durotomy. A comparison of surgeon training showed no statistically significant difference in durotomy rate between fellowship and non-fellowship trained surgeons, or between orthopedic surgeons and neurosurgeons. The PSO level, PSO aggressiveness, the presence of stenosis at the PSO level, nor the surgical instrument used predicted the odds of durotomy occurrence. Those experiencing durotomy had similar hospitalization durations, rates of reoperation and rates of nonroutine discharge. Conclusions: In this large multisite series, a history of prior decompression at the PSO level was associated with a four-fold increase in intraoperative durotomy risk. Notably the use of extended (versus) standard PSO, surgical technique, nor baseline patient characteristics predicted durotomy. Durotomies occurred in 44% of patients and may prolong operative times. Additional prospective investigations are merited.

Summary: EEG source imaging is an established technique for identifying the origin of interictal and ictal epileptiform discharges in patients with epilepsy, and it is an important tool in neurophysiology research. Accurate and reliable EEG source imaging requires appropriate choices of how the head, skull, and scalp are modeled, and understanding of the different approaches to modeling is important to guide these choices. Similarly, numerous different approaches to modeling the electrical sources within the brain exist, and appropriate understanding of the strengths and limitations of each are essential to obtaining accurate, reliable, and interpretable solutions. This review aims to describe the essential theoretical basis for these head and source models while also discussing the practical implications of each in clinical or research applications.

ABSTRACTObjectiveMost Helicobacter pylori infections are acquired during childhood. The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) recently published practice guidelines for managing pediatric H. pylori infection. Before this publication, the authors conducted a survey to assess pediatric gastroenterologists' knowledge and practices regarding H. pylori.MethodsOne hundred nine of 514 NASPGHAN members completed an Internet‐based questionnaire on H. pylori infection.ResultsEighty‐two percent of respondents performed outpatient testing for H. pylori. Of these, only 31% restricted testing to children aged >5 years. Most recommended testing for H. pylori in guideline‐recommended conditions; some would not treat infected patients. Ninety‐seven percent would test for H. pylori in a child with new duodenal ulcer (DU), 79% in a child with a history of DU, and 91% in a child with new gastric ulcer. However, only 86%, 60%, and 91%, respectively, would treat H. pylori infection in those conditions. A proton pump inhibitor (PPI)‐based triple regimen was the first‐choice therapy for 78% of respondents. Correct estimates of rates of resistance to amoxicillin, clarithromycin, metronidazole, and tetracycline were 10%, 17%, 43%, and 12%, respectively. Eighty‐six percent believed there was insufficient research on H. pylori in children.ConclusionsNorth American pediatric gastroenterologists seem well informed about H. pylori infection in children despite the lack of published guidelines at the time of survey. Knowledge about antibiotic resistance rates was deficient. Most offered some outpatient testing for H. pylori and would test children with ulcer disease. However, some would not treat patients based on a positive result.

Background Communication gaps, whether incomplete or fragmented communication, have been the cause of many disasters in human civilisation. Coordination of healthcare is directly related to proper communication and handoffs among multidisciplinary teams throughout multiple shifts during a patient’s hospitalisation. Local problem Patient surveys and direct patient feedback at Mayo Clinic Health System in Mankato, Minnesota, indicated that patient communication with physicians and nurses had declined in 2017 and 2018. Viewing this as an opportunity for improvement, our leadership initiated several changes to increase physician and nurse communication with patients, which resulted in no notable improvements. Methods A systematic quality improvement approach was implemented by using Six Sigma methodology. Stakeholders from multidisciplinary teams were assembled as the project team. The five steps of Six Sigma methodology (Define, Measure, Analyse, Improve and Control) were followed to create a quality improvement intervention. Intervention We developed a standardised and easy-to-use bedside team rounding tool to improve patient communication with physicians and nurses. Results Postintervention patient satisfaction top-box scores exceeded target improvements for both physician (from 78.5% to 82.0%, p<0.01) and nurse (from 80.5% to 83.1%, p=0.04) communication domains. Physicians had a 33-point increase in percentile rank (from 41st to 74th percentile rank), and nurses had a 25-point increase in percentile rank (from 59th to 84th percentile rank). This increase in communication ranked our institution at the top of national benchmark organisations. Conclusions Overwhelmingly positive patient feedback was achieved, and postintervention employee satisfaction was primarily positive when compared with preintervention satisfaction.

Background: Metacarpophalangeal (MCP) joint arthritis is common secondary to a variety of inflammatory, degenerative, and traumatic causes. Although MCP arthroplasty is more common for the second to fifth digits, primary arthrodesis can be used for high-demand patients with arthritis or unsalvageable fractures of the MCP joint. There has been limited recent studies on the outcomes of these patients. Methods: A retrospective review of 38 fingers in 27 patients with primary arthrodesis from 1990 to 2020 was conducted. The major outcomes were complications, reoperations, radiographic union, and time to union. Patient-reported outcomes including the Michigan Hand Outcomes Questionnaire and a questionnaire specific to the operative MCP joint were collected. Results: Rate of radiographic union was 84% including revisions. The average time to union was 3.6 months. Rates of complications, reoperation, and amputation were 26%, 16%, and 7%, respectively. Arthrodesis as part of emergent trauma reconstruction was significantly more likely to result in reoperation (50% vs 7%) and complication (63% vs 17%) than chronic arthritis. Patient-reported outcomes were fair to good with improvement in pain (79%), function (66%), and appearance (40%). Sixty-six percent (66%) of patients were satisfied with their surgery, and 73% would repeat the surgery. Conclusion: Arthrodesis for unsalvageable MCP fractures was associated with higher rates of reoperation and complication than inflammatory or degenerative arthritis. Excluding emergent trauma, MCP fusion was reliable with a reoperation rate of 7% and a modest complication rate of 17%. Patients rated reasonable levels of satisfaction and willingness to repeat the procedure despite complications.

Abstract Refinement of breast cancer risk estimates with a polygenic-risk score (PRS) may improve uptake of risk-reducing endocrine therapy (ET). A previous clinical trial assessed the influence of adding a PRS to traditional risk estimates on ET use. We stratified participants according to PRS-refined breast cancer risk and evaluated ET use and ET-related quality of life (QOL) at 1-year (previously reported) and 2-year follow-ups. Of 151 participants, 58 (38.4%) initiated ET, and 22 (14.6%) discontinued ET by 2 years; 42 (27.8%) and 36 (23.8%) participants were using ET at 1- and 2-year follow-ups, respectively. At the 2-year follow-up, 39% of participants with a lifetime breast cancer risk of 40.1% to 100.0%, 18% with a 20.1% to 40.0% risk, and 16% with a 0.0% to 20.0% risk were taking ET (overall P = 0.01). Moreover, 40% of participants whose breast cancer risk increased by 10% or greater with addition of the PRS to a traditional breast cancer-risk model were taking ET versus 0% whose risk decreased by 10% or greater (P = 0.004). QOL was similar for participants taking or not taking ET at 1- and 2-year follow-ups, although most who discontinued ET did so because of adverse effects. However, these QOL results may have been skewed by the long interval between QOL surveys and lack of baseline QOL data. PRS-informed breast cancer prevention counseling has a lasting, but waning, effect over time. Additional follow-up studies are needed to address the effect of PRS on ET adherence, ET-related QOL, supplemental breast cancer screening, and other risk-reducing behaviors. Prevention Relevance: Risk-reducing medications for breast cancer are considerably underused. Informing women at risk with precise and individualized risk assessment tools may substantially affect the incidence of breast cancer. In our study, a risk assessment tool (IBIS-polygenic-risk score) yielded promising results, with 39% of women at highest risk starting preventive medication.

AbstractBackgroundTriplication of the APP allele in Down syndrome (DS) leads to excess amyloid production and Alzheimer’s disease (AD) related cognitive decline. Key biomarkers (amyloid, tau, neurodegeneration) can identify pathological processes that occur before clinical symptoms and more precisely stage adults with DS along the AD continuum. Previous research has used changes in cortical thickness (CT) as an indicator of neurodegeneration in autosomal‐dominant AD1, but not DS‐related AD. It is unclear when and where cortical thinning occurs along the AD continuum in DS and if these differences are associated with increasing AD pathology.MethodCross‐sectional analysis compared DS participants from the Alzheimer Biomarkers Consortium‐Down Syndrome (106 amyloid‐/cognitively unimpaired, nonclinical, 20% reserved for receiver‐operating characteristic, ROC, analyses; 45 amyloid+/cognitively unimpaired, preclinical; 27 amyloid+/cognitively impaired, clinical) who had amyloid positron emission tomography and magnetic resonance imaging (MRI). Amyloid positivity was defined using standardized uptake value ratio (partial volume corrected) cortical mean values (1.42/1.19 for PIB/AV452) and impairment was based on consensus diagnosis. CT differences between nonclinical and clinical groups were calculated in FreeSurfer v5.3 for multiple thresholds (p<.05/.01/.005/.001/.0005/.0001) using a cluster‐wise false discovery rate of .001, corrected across hemispheres, after controlling for age and sex. CT values were extracted for each threshold and used in ROC analyses (nonclinical reserved participants compared against preclinical and preclinical compared against clinical) to identify key cortical regions that best discriminated amyloid positivity and between unimpaired and impaired.ResultSignificant decreases in parietal and inferior temporal CT were observed between nonclinical and clinical (Figures 1 and 2). ROC analyses identified regions in the left (threshold .05) and right (threshold .005) hemispheres that best differentiated nonclinical from preclinical. Observed area under the curves (AUCs) of .772 and .830 exceeded those previously reported for autosomal‐dominant AD (.547/.540)1. Analyses differentiating preclinical from clinical observed AUCs of .786 for left (threshold .0005) and .770 for right (threshold .0005) hemispheres.ConclusionCT differences primarily within posterior cortical regions differentiated adults with DS by amyloid status and cognitive impairment. CT differences were more diffuse for amyloid positivity but more focal for impairment.1. Dincer (2020). NeuroImage: Clinical, 28, 102491.2. Su (2019). Alzheimer’s Dement, 11, 180‐190.