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Despite significant improvements in survival of patients with multiple myeloma (MM), outcomes remain heterogeneous, and a significant proportion of patients experience suboptimal outcomes. Importantly, traditional prognostic factors based on data from patients treated with older therapies no longer capture prognosis accurately in the contemporary era of novel triplet or quadruplet therapies. Therefore, risk stratification requires refinement in the context of available and investigational treatment options in routine practice and clinical trials, respectively. The current identification of high-risk MM (HRMM) in routine practice is based on the Revised International Staging System, which stratifies patients using a combination of widely available serum biomarkers and chromosomal abnormalities assessed via fluorescence in situ hybridization. In recent years, a substantial body of evidence concerning additional clinical, biological, and molecular/genomic prognostic factors has accumulated, along with new MM risk stratification tools and consensus reports. The International Myeloma Society, along with the International Myeloma Working Group, convened an Expert Panel with the primary aim of revisiting the definition of HRMM and formulating a practical and data-driven consensus definition, based on new evidence from molecular/genomic assays, updated clinical data, and contemporary risk stratification concepts. The Panel proposes the following Consensus Genomic Staging (CGS) of HRMM which relies upon the presence of at least one of these abnormalities: (1) del(17p), with a cutoff of >20% clonal fraction, and/or TP53 mutation; (2) an IgH translocation including t(4;14), t(14;16), or t(14;20) along with 1q+ and/or del(1p32); (3) monoallelic del(1p32) along with 1q+ or biallelic del(1p32); or (4) β2 microglobulin ≥5.5 mg/L with normal creatinine (<1.2 mg/dL).

PURPOSE To compare overall survival (OS) in patients with baseline metastatic gastric adenocarcinoma (GA) with and without ovarian metastasis (OM). Furthermore, within the group that had ovarian metastases, we aimed to assess whether there was a survival benefit (SB) with palliative oophorectomy (PO). PATIENTS AND METHODS This is a single-institution retrospective analysis of the clinicopathological features of women diagnosed with metastatic GA with a comparison of outcomes based on PO status. We identified 240 women with baseline metastatic GAs who were treated at MD Anderson Cancer Center between February 2003 and September 2022. Among these women, we categorized a subgroup of 102 women who had OM from their primary GA. Patients were analyzed whether they underwent PO. RESULTS Patients who developed OM were most often non-Caucasian, had peritoneal involvement, and had tumors that were both human epidermal growth factor receptor 2–negative and PD-L1–negative, with signet ring cell features and diffuse histological type. Among patients with ovarian metastases, those who had PO had an Eastern Cooperative Oncology Group = 0, more comprehensive molecular and immunohistochemical profiling, lower percentage of family history of gastroesophageal malignancies, and lower interval between diagnosis of the GA primary and the OM. PO was associated with significantly improved OS in this subgroup (hazard ratio, 0.5 [95% CI, 0.31 to 0.81]; P = .005). CONCLUSION To our knowledge, this is the largest multiethnic population study assessing SB of PO in patients with GA with OM. Additionally, it is the largest study analyzing survival in this population according to the patient's multiethnic characteristics and metastasis timing and growth patterns. PO presents as a therapeutic option for women with GAs with OM if the patient is clinically suitable for surgical resection.

BACKGROUND AND OBJECTIVES: Aneurysm risk prediction remains an imprecise science that places patients at risk for either over or undertreatment. Machine learning (ML) models may improve clinical practice by adding precision to risk assessment. This study aims to comprehensively assess the current landscape of ML applications in predicting the risk of aneurysm rupture and compare the performance with the widely used PHASES score. METHODS: A systematic review of PubMed, Scopus, and Web of Science was conducted. All studies using ML tools to predict the rupture risk of intracranial aneurysms were included. Meta-analysis was conducted with consideration to the ML algorithms and compared with the PHASES score. RESULTS: Thirty-six studies involving 22 462 patients were included in the final analysis. ML techniques, including 124 models using 25 algorithms, were employed. Among various ML models, while they had comparable diagnostic performance, deep learning exhibited a slightly better performance profile (sensitivity = 0.792, specificity = 0.788, and accuracy = 0.778 in external validation). Based on our analysis, ML, regardless of the algorithm, provides comparable sensitivity (0.743 vs 0.771, P = .60) and higher specificity (0.763 vs 0.507, P < .01) compared with the PHASES score. Consistently, pooling the area under the receiver operating characteristic curve (AUC) for 60 ML models and 5 PHASES score data, ML models exhibited higher AUC (0.84 vs 0.64, P < .01). Using hemodynamic parameters as input for models improved specificity ( P < .01) in the test sets without any significant changes in the sensitivity. The later improvement was not observed in the external validation sets. CONCLUSION: ML techniques have the potential to enhance the prediction of intracranial aneurysm rupture compared with traditional approaches, like the PHASES score. Incorporating hemodynamic parameters may further enhance the accuracy of ML models. Feature prospective studies are required to validate the utility of ML models for clinical integration.

10019 Background: The reported incidence of second malignant neoplasms (SMN) in long-term survivors of Hodgkin lymphoma (HL) is derived from patients treated with outdated radiation therapy (RT) techniques. We modeled the risk of SMN in pediatric patients with high-risk classic HL treated with modern mediastinal RT. Methods: In patients who received mediastinal RT on the Children’s Oncology Group study AHOD1331, we modeled the lifetime attributable risk (LAR) at 70 years of age of thyroid, lung, and breast carcinoma. This value indicates the absolute increased risk of SMN at 70 years of age due to RT, above the baseline population risk (mean baseline rates at 70 years of age are 0.7%, 3.3%, and 8.9% for thyroid, lung, and breast carcinoma, respectively, https://seer.cancer.gov/data/ ). Results: In 296 patients who received protocol-directed mediastinal RT, median age at diagnosis was 15.1 years, 55% were female, and 98% had large mediastinal adenopathy. Following 5 cycles of chemotherapy, patients received RT targeting the mediastinum based on criteria of this study; in addition, some patients received RT to other supradiaphragmatic sites that contained slowly responding lesions, including the axilla (n = 3, 1%), lung (n = 7, 2.4%), upper neck (n = 4, 1.3%), and lower neck (n = 8, 2.7%). The RT modality was proton therapy in 25.3%, photon intensity modulated RT (IMRT) in 45.6%, and photon 3-dimensional conformal RT (3D-CRT) in 27.7%. The RT prescription dose was 21 Gy in 83% and 30 Gy in 16% who had a partial metabolic response at the completion of chemotherapy. The mean (range) doses to the thyroid, lungs, and breasts were 12.8 Gy (0-30.3), 8.0 Gy (0.1-15.2), and 4.2 Gy (0.2-14.5), respectively. For the complete cohort, the mean LAR at 70 years of age of thyroid carcinoma was 0.063% and of lung carcinoma was 5.34%. For females, the mean LAR at 70 years of age of breast carcinoma was 2.92%. The Table summarizes the LAR for each SMN, stratified by RT modality. Conclusions: In patients treated with mediastinal RT on a recent multi-institutional study of pediatric HL, the predicted long-term risk of SMN is substantially lower than in historical cohorts. Clinicians should consider the toxicity associated with a current RT approach when selecting therapies and counseling patients. Clinical trial information: NCT02166463 , this is a post hoc modeling study that includes patients enrolled on this study. Mean [range] lifetime attributable risk (%) at an attained age of 70 years for thyroid, lung, and breast carcinoma. Thyroid Lung Breast (females) 3D-CRT 0.046 [0.002-0.332]N=81 5.07 [0.12-10.82]N=82 1.82 [0.67-5.98]N=46 IMRT 0.064 [0.001-0.386]N=135 6.24 [2.22-11.79]N=135 4.36 [0.66-8.43]N=76 Proton 0.086 [0-1.160]N=74 4.15 [0.94-7.77]N=75 1.45 [0.17-7.23]N=40

OBJECTIVE Cervical spondylotic myelopathy (CSM) is often accompanied by neck pain, which, along with more recognized neurological deficits like motor and sensory changes, significantly impacts patients’ quality of life. The authors examined whether age influences improvements in neck disability and related quality-of-life measures after surgery for CSM. Using the Neck Disability Index (NDI) as the primary outcome, they compared long-term outcomes at 24 months among patients aged ≥ 65, ≥75, and < 65 years, exploring the effects of surgical intervention on both pain-related disability and functional recovery in older adults. METHODS Using the Quality Outcomes Database, the authors conducted a detailed propensity score–matched analysis on cohorts aged ≥ 65 and ≥ 75 years compared with a < 65-year-old cohort while controlling for baseline NDI scores, other demographic variables, health status, underlying pathology, number of levels, indication for surgery, surgical approach, and type of surgery. Differences in NDI total and subdomain scores at 24 months postoperatively were the primary measures of improvement. Age-related variability in NDI differential was assessed. EQ-5D and calculated SF-6D were secondary measures. RESULTS Of the 1141 patients in the cohort (January 2016 to December 2018), 687 patients were < 65 years, 325 were 65 to < 75 years, and 129 were ≥ 75 years of age. After propensity score matching, 197 patients each were well matched in the ≥ 65-year (mean 71.4 years) and < 65-year (mean 55.3 years) cohorts; similarly, 57 patients each were matched in the ≥ 75-year (mean 78.3 years) and < 65-year (mean 55.8 years) cohorts. Improvements in NDI scores and subdomain scores, EQ-5D, and calculated SF-6D were consistent at 3, 12, and 24 months postoperatively across all cohorts. At 24 months, patients ≥ 65 years showed NDI score improvements (−14.7 ± 22.3) similar to those < 65 years (−13.0 ± 21.3, p = 0.454), and patients ≥ 75 years demonstrated NDI improvements (−15.0 ± 19.7) comparable to those < 65 years (−17.6 ± 20.4, p = 0.499). A sensitivity analysis for linear relationship found that NDI improvement was statistically greater in older patients (7.5 points every 30 years, p < 0.0001), but this difference was below the minimal clinically important difference. Other clinical outcomes were similar between cohorts. CONCLUSIONS Surgical intervention for CSM yields substantial and similar improvements in NDI scores and other metrics among various age groups, including those aged at least 65 and 75 years. These results highlight the effectiveness of surgery across a broad patient demographic, underscoring its value in treating CSM irrespective of age.

BACKGROUND AND OBJECTIVES: There has been limited assessment between anterior cervical diskectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) on patient-reported outcome measures (PROMs) in the treatment of cervical spondylotic myelopathy. We sought to compare PROMs from two-level ACDF with single-level ACCF procedures. We evaluate these results in the context of minimum clinically important difference (MCID) thresholds, which have not been performed previously. METHODS: This retrospective analysis of prospectively collected data from the Quality Outcomes Database Spine Collaborative Research Study Group compared two-level ACDF and single-level ACCF at 3-, 12-, and 24 months postoperatively. PROMs included arm pain Numeric Rating Scale, neck pain Numeric Rating Scale, Neck Disability Index, and North American Spine Society Patient Satisfaction Index. Multivariate logistic regression was used to determine differences in perioperative outcomes, as well as the impact of two-level ACDF vs one-level ACCF on PROMs. MCID thresholds were based off previously established limits. RESULTS: Three hundred and thirty patients were included (236 ACDF, 94 ACCF), and the follow-up rate was 82% at 2 years. There was a significantly higher baseline age, American Society of Anesthesiologists grade, proportion of diabetes, osteoarthritis, ambulation dependence, and myelopathy severity in the ACCF cohort. On multivariable analysis, the ACCF group had greater average length of stay and estimated blood loss. There were no significant differences between reoperation rates or nonroutine discharge. There were similar rates of MCID achievement for PROMs at all time points. CONCLUSION: This study suggests that both ACDF and ACCF procedures for cervical spondylotic myelopathy are able to achieve similar, clinically meaningful improvements in PROMs by 2 years. Patients undergoing single-level ACCF have more estimated blood loss and longer length of stay, as well as worse baseline myelopathy. Both procedures have efficacious, durable outcomes. It is reasonable that other factors, such as radiographic characteristics and patient symptoms, may influence patient selection for ACDF vs ACCF.

ABSTRACT Background and hypothesis Podocytopathy associated with likely pathogenic/pathogenic variants of Transient receptor potential cation channel subfamily C member 6 (TRPC6) (TRPC6-AP) has been recognized for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype–phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterized clinical, histological and genetic correlates of familial and sporadic patients with TRPC6-AP. Methods In this multicentre observational study, an online questionnaire followed by a systematic literature review was performed to create a cohort with comprehensive data on genetic and clinical outcomes [age of onset, clinical presentation, treatment response, kidney biopsy findings and progression to kidney failure (KF)]. Logistic regression, Cox proportional hazards model and Kaplan–Meier analyses investigated the associations between genetic variants and disease progression. Results Among 87 families (96 familial and 45 sporadic cases), 31 distinct missense TRPC6 variants (including 2 novel) were identified, with c.2683C&gt;T p.(Arg895Cys) and c.523C&gt;T p.(Arg175Trp) the commonest variants. Proteinuric kidney disease/nephrotic syndrome was the most common clinical presentation (83.7%), while focal segmental glomerulosclerosis was the most common histological finding (89.4%). By 33 (interquartile range 17–40) years, 48.9% (69/141) of patients had progressed to KF. Sporadic TRPC6-AP demonstrated an earlier progression to KF than familial cases (P = .001) and were more likely to present with nephrotic syndrome [odds ratio 4.34 (1.85–10.15); P = .001]. Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs 44.4%; P = .004). Compared with patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to KF earlier [median kidney survival of 21 years, hazard ratio 2.985 (95% confidence interval 1.40–5.79); and 38 years, hazard ratio 1.65 (95% confidence interval 1.01–2.81), respectively, log-rank P = .005]. Conclusion Our study shows unique clinical and genetic correlations of TRPC6-AP, which may enable personalized care and promising novel therapies.

Abstract Background Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. Objective To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. Methods The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. Results In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations. In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC—including contraception as a key component—showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception. In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy. In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition. In individuals with PDM, we suggest either a carbohydrate-restricted diet (&lt;175 g/day) or usual diet (&gt;175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day. In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM. In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target &lt;140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting &lt;95 mg/dL (5.3 mmol/L), 1-hour postprandial &lt;140 mg/dL (7.8 mmol/L), and 2-hour postprandial &lt; 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose &gt; 126 mg/dL (7 mmol/L). In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI −4.24 to 11.86) and reduced time below range (MD −0.88%; 95% CI: −2.04 to 0.27) with the use of hybrid closed-loop pump technology. In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing. In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. Conclusion The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

Abstract Rationale: The US prison population carries a high burden of chronic disease and disability, with older adults constituting the fastest growing subpopulation. When medical needs exceed a prison's healthcare service capabilities, incarcerated patients are transported to clinics and hospitals in surrounding communities. The influence of prison policies on off-site medical care of incarcerated patients is poorly understood. This study aims to identify and classify correctional policies regulating the care of incarcerated patients in community hospitals. Methods: Between 6/2024-10/2024 we searched the Internet for policies from states’ Departments of Corrections (DOC) pertaining to healthcare of incarcerated patients. We compiled, reconciled and organized those policies according to date, jurisdiction and relevance to hospital care. We then developed a preliminary thematic coding scheme and, using mixed inductive and deductive content analysis, two coders independently applied our codebook to each policy. Any coding discrepancies were resolved by consensus, and when necessary, with adjudication by a third team member. Results: Forty-eight state DOCs and the District of Columbia (totaling 49 “states”) have publicly available policies pertaining to healthcare. Among these, 20/49 (41%) have policies pertaining to the protection of bodily privacy during healthcare encounters. Separately, 31 (63%) have policies regarding the confidentiality of incarcerated patients’ medical encounters and records. Thirty-four (69%) maintain policies regarding incarcerated individuals’ right to select and consent to treatment. Thirty-three (67%) include language about the right to refuse treatment. Twenty-six states (53%) direct that incarcerated individuals be informed of their right to access healthcare either in writing (22/49; 45%), verbally (20/49; 41%), or through posted signage (5/49; 10%). Twenty-one states (43%) address shackling during off-site medical care, but only 15 (31%) address responding to requests from off-site clinicians to minimize or remove patients’ restraints. Just 4/49 states (8%) use person-centered language (avoiding terms like “offender” and “inmate”). Policy excerpts addressing key domains are depicted in the Table. Conclusions: Correctional policies regarding the care of incarcerated patients in community hospitals vary significantly in scope and content across states. While incarcerated people have a Constitutionally protected right to accept or refuse healthcare, including making their own treatment decisions, many state policies do not explicitly mandate how these disclosures must be communicated to patients or their healthcare providers. These silences, when combined with security measures like shackling and the ubiquitous presence of officers, countermand person-centered care and undermine the ability of hospital healthcare professionals to uphold the rights and dignity of incarcerated patients.

Objective To develop and validate classification criteria for pediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by EULAR and the American College of Rheumatology (ACR). Methods This international initiative had 4 phases: (1) candidate items were proposed in a survey of pediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. Results The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anemia, C‐reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. Conclusion These new classification criteria for pediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.