Sleep-related painful erections treated with sodium oxybate.

A 39-year-old male with a medical history significant for migraine, psoriatic arthritis, postural orthostatic tachycardia syndrome, vitamin D deficiency, and hypoglycemia presented with a 2-year history of sleep-related painful erections. Because the reported prevalence is low, there is limited understanding of the possible etiologies of the disorder and few published clinical data on treatment algorithms. Thus, he had tried multiple therapies. Baclofen was effective but not tolerated. Pelvic physiotherapy and tadalafil were ineffective. Imipramine, clonazepam, vitamin B, iron, and selenium provided minimal benefit. Opiates were initially effective but lost efficacy after 2-3 weeks. Finally, he was started on sodium oxybate after fully counseling the patient on the potential side effects of the treatment and consenting the patient for off-label use. This has effectively treated his sleep-related painful erections. Sodium oxybate is a novel therapy for and a possible new treatment for this rare and challenging disorder that merits further study. CITATION: Chaudhary HS, Zeidman E, Punjani N, Tashman Y. Sleep-related painful erections treated with sodium oxybate. J Clin Sleep Med. 2024;20(7):1209-1211.

First Line Treatment of Newly Diagnosed Transplant Ineligible Multiple Myeloma: Recommendations from the Canadian Myeloma Research Group Consensus Guideline Consortium.

Although the availability of effective novel treatments has positively impacted the quality of life and survival of newly diagnosed multiple myeloma (MM) patients, benefits in the transplant ineligible MM population may be limited by functional/frailty status. The Canadian Myeloma Research Group Consensus Guideline Consortium proposes consensus recommendations for the first-line treatment of transplant ineligible MM. To address the needs of physicians and people diagnosed with MM, this document further focuses on eligibility for transplant, frailty assessment, management of adverse events, assessment of treatment response, and monitoring for disease relapse. The Canadian Myeloma Research Group Consensus Guideline Consortium will periodically review the recommendations herein and update as necessary.

Fluorescence molecular optomic signatures improve identification of tumors in head and neck specimens.

Background: Fluorescence molecular imaging using ABY-029, an epidermal growth factor receptor (EGFR)-targeted, synthetic Affibody peptide labeled with a near-infrared fluorophore, is under investigation for surgical guidance during head and neck squamous cell carcinoma (HNSCC) resection. However, tumor-to-normal tissue contrast is confounded by intrinsic physiological limitations of heterogeneous EGFR expression and non-specific agent uptake. Objective: In this preliminary study, radiomic analysis was applied to optical ABY-029 fluorescence image data for HNSCC tissue classification through an approach termed "optomics." Optomics was employed to improve tumor identification by leveraging textural pattern differences in EGFR expression conveyed by fluorescence. The study objective was to compare the performance of conventional fluorescence intensity thresholding and optomics for binary classification of malignant vs. non-malignant HNSCC tissues. Materials and Methods: Fluorescence image data collected through a Phase 0 clinical trial of ABY-029 involved a total of 20,073 sub-image patches (size of 1.8 × 1.8 mm2) extracted from 24 bread-loafed slices of HNSCC surgical resections originating from 12 patients who were stratified into three dose groups (30, 90, and 171 nanomoles). Each dose group was randomly partitioned on the specimen-level 75%/25% into training/testing sets, then all training and testing sets were aggregated. A total of 1,472 standardized radiomic features were extracted from each patch and evaluated by minimum redundancy maximum relevance feature selection, and 25 top-ranked features were used to train a support vector machine (SVM) classifier. Predictive performance of the SVM classifier was compared to fluorescence intensity thresholding for classifying testing set image patches with histologically confirmed malignancy status. Results: Optomics provided consistent improvement in prediction accuracy and false positive rate (FPR) and similar false negative rate (FNR) on all testing set slices, irrespective of dose, compared to fluorescence intensity thresholding (mean accuracies of 89% vs. 81%, P = 0.0072; mean FPRs of 12% vs. 21%, P = 0.0035; and mean FNRs of 13% vs. 17%, P = 0.35). Conclusions: Optomics outperformed conventional fluorescence intensity thresholding for tumor identification using sub-image patches as the unit of analysis. Optomics mitigate diagnostic uncertainties introduced through physiological variability, imaging agent dose, and inter-specimen biases of fluorescence molecular imaging by probing textural image information. This preliminary study provides a proof-of-concept that applying radiomics to fluorescence molecular imaging data offers a promising image analysis technique for cancer detection in fluorescence-guided surgery.

Antiproliferative activity and electrochemical oxygen evolution by Ni(II) complexes of N'-(aroyl)-hydrazine carbodithioates.

The electrochemical water splitting by transition metal complexes is emerging very rapidly. The nickel complexes also play a very vital role in various biological activities. Here, three new ligands {H2mbhce = N'-(4-methyl-benzoyl), H2pchce = N'-(pyridine-carbonyl) and H2hbhce = N'-(2-hydroxy-benzoyl) hydrazine carbodithioic acid ethyl ester} and their corresponding Ni(II) complexes [Ni(Hmbhce)2(py)2] (1), [Ni(pchce)(o-phen)2]·CH3OH·H2O (2) and [Ni(hbhce)(o-phen)2]·1.75CHCl3·H2O (3) have been synthesized and fully characterized by various physicochemical and X-ray crystallography techniques. The photoluminescence study and thermal degradations were also examined. The treatment of K562 cells with the increasing concentrations of the nickel salts, ligands, and complexes 1, 2, and 3 showed dose-dependent cytotoxicity. The cytotoxic activity of ligands reveals that ligand H2mbhce is more potent in inhibiting the growth of tumor cells in comparison to other ligands H2pbhce and H2hbhce. Cytotoxicity assay results indicate that all complexes have remarkable cytotoxic potential in comparison to either nickel salts or the free ligands. Among these complexes, complex 1 has significantly better anti-tumor activity as compared to complexes 2 and 3. The electrochemical study of complexes 1, 2, and 3 for water oxidation reveals that all the complexes possess admirable electrocatalytic activity towards oxygen evolution reaction (OER) and have lower overpotential (328, 338, and 370 mV, respectively) than many previously reported complexes and RuO2 (390 mV). Among complexes 1, 2, and 3, complex-2 shows a better water oxidation response. Consequently, these complexes have great potential to be utilized in fuel cells. The more reliable electrochemical parameter TOF is also calculated for all three complexes.

Renal failure among multiple myeloma patients utilizing carfilzomib and associated factors in the "real world".

Carfilzomib, a next-generation proteasome inhibitor, improves outcomes in patients with multiple myeloma (MM); however, a proportion of those treated develop renal failure due to adverse event, comorbidity, or myeloma progression. The rate of renal failure and associated risk factors remains unknown in real-world populations. Adults with relapsed/refractory MM who received carfilzomib between the years 2013 and 2016 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Renal failure was defined using the corresponding International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) diagnostic codes and procedure codes for dialysis. Patients with a pre-existing diagnosis of renal failure were excluded to distinguish an adverse event from comorbidity. Multivariate cox regression analysis was performed to identify the variables independently associated with the development of renal failure among MM patients utilizing carfilzomib. A total of 1950 patients were included in the analysis. Renal failure developed in 22% of patients during the study period. The median time to development of renal failure from first carfilzomib administration was 1.6 months (range < 0.1-23.3). Increasing age (adjusted hazard ratio [aHR] 1.01 per year, p = 0.018), pre-existing heart failure (aHR 1.50, p = 0.005), and pre-existing chronic kidney disease (aHR 2.00, p < 0.001) were associated with a higher risk of developing renal failure. Renal failure occurred in up to 22% of patients on carfilzomib therapy. The exact cause and mechanism of renal failure cannot be determined from our study and may be multifactorial. Future studies are needed to further understand the cause of renal failure among patients on carfilzomib and devise strategies to mitigate the risk.

Symptom burden in transplant ineligible patients with newly diagnosed multiple myeloma: a population-based cohort study.

Not available.

Transplant-ineligible newly diagnosed multiple myeloma: Current and future approaches to clinical care: A Young International Society of Geriatric Oncology Review Paper.

Multiple myeloma is the second most common hematological malignancy in the USA and Europe. Despite improvements in the 5-year and overall survival rates over the past decade, older adults (aged ≥65 years) with multiple myeloma continue to experience disproportionately worse outcomes than their younger counterparts. These differences in outcomes arise from the increased prevalence of vulnerabilities such as medical comorbidities and frailty seen with advancing age that can influence treatment-delivery and tolerance and impact survival. In general, geriatric assessments can help identify those patients more likely to benefit from enhanced toxicity risk-prediction and aid treatment decision-making. Despite the observed benefits of geriatric assessments and other screening frailty tools, provider and systems-level barriers continue to influence the overall perception of the feasibility of geriatric assessments in clinical practice settings. Clinical trials are underway evaluating the efficacy and safety of various multiple myeloma therapies in less fit/frail older adults, with a minority examining fitness-based/risk-adapted approaches. Thus, significant gaps exist in knowing which myeloma therapies are most appropriate for older and more vulnerable adults with multiple myeloma. The purpose of this Review is to discuss how geriatric assessments can be used to guide the management of transplant-ineligible patients; and to highlight frontline therapies for standard-risk and high-risk cytogenetic abnormalities [i.e., t(4;14), t(14;16), and del(17p)] associated with multiple myeloma. We also discuss the current shortcomings of the existing clinical approaches to care and highlight ongoing clinical trials evaluating newer fitness-based approaches to managing transplant-ineligible patients.

Burden of Treatment Among Older Adults With Newly Diagnosed Multiple Myeloma.

BACKGROUND: Multiple myeloma is an incurable hematologic malignancy with significant recent treatment advances; however, the magnitude of treatment burden among patients in the first year after diagnosis has yet to be fully researched and reported. PATIENTS AND METHODS: Patients with multiple myeloma newly diagnosed between 2007 and 2013 were identified in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases. Treatment burden was captured as the number of total days with a health care encounter (including acute care and outpatient visits), oncology and nononcology physician visits, and the number of new prescriptions within the first year after diagnosis. Logistic regression was used to identify factors associated with high treatment burden. RESULTS: A total of 3065 patients were included in the analysis. There was a substantial burden of treatment within the first year after diagnosis (median, 77 days; interquartile range, 55-105 days), which was highest during the first 3 months. Patients with high comorbidities (adjusted odds ratio [aOR] 1.27 per 1-point increase in Charlson comorbidity index, P < .001), poor performance status (aOR 1.85, P < .001), myeloma-related end organ damage, particularly bone disease (aOR 2.28, P < .001), and those who underwent autologous stem-cell transplantation (aOR 2.41, P < .001) were more likely to have a higher treatment burden. CONCLUSION: There is considerable burden of treatment in patients with newly diagnosed multiple myeloma within the first year after diagnosis, particularly within the first 3 months. Future tailored interventions aimed at optimizing this treatment burden when possible while simultaneously providing support to manage it may improve patient-centered care.

Disparities in treatment patterns and outcomes among younger and older adults with newly diagnosed multiple myeloma: A population-based study.

INTRODUCTION: Multiple myeloma, a cancer of older adults, has seen significant improvement in therapeutic options over the past two decades. Uncovering disparities in treatment patterns and outcomes is imperative in order to ensure older adults, who are underrepresented in clinical trials, are benefitting from these advances. METHODS: Adults with newly diagnosed multiple myeloma (NDMM) were identified using linked provincial administrative databases between 2007 and 2017 in Ontario, Canada. Trends in rate of no treatment, novel drug and autologous stem cell transplant (ASCT) usage was evaluated within one year following diagnosis along with the associated early mortality (<12 months) for the aforementioned cohorts among younger (≤65 years) and older adults (>65 years) with NDMM. RESULTS: A total of 8841 adults with NDMM were identified. Rates of no treatment decreased in both age groups during the study period; however still remain considerably high among older patients (from 34.9% in 2007 to 27.4% in 2017) with high associated early mortality in the older untreated group (54.1% 1 yr mortality over study period). Despite increased usage of novel drugs in both age groups, early mortality decreased among younger patients utilizing novel drugs (16.1% to 5.6%) but remained high and stagnant in older patients using novel drugs (18.2% 1 yr mortality over study period). ASCT utilization increased in both age groups during the study period with decreasing early mortality among older patients undergoing ASCT (from 26.3% in 2007 to 1.1% in 2017). CONCLUSION: While several improvements have been made, rates of no treatment and early mortality among patients not treated and those started on novel drugs remains a concern in older adults with NDMM.

Dual-agent fluorescent labeling of soft-tissue sarcomas improves the contrast based upon targeting both interstitial and cellular components of the tumor milieu.

BACKGROUND: Current practices for fluorescence-guided cancer surgery utilize a single fluorescent agent, but homogeneous distribution throughout the tumor is difficult to achieve. We hypothesize that administering a perfusion and a molecular-targeted agent at their optimal administration-to-imaging time will improve whole-tumor contrast. EXPERIMENTAL DESIGN: Mice bearing subcutaneous xenograft human synovial sarcomas were administered indocyanine green (ICG) (3 mg/kg) or ABY-029 (48.7 µg/kg)-an epidermal growth factor receptor-targeted Affibody molecule-alone or in combination. Fluorescence contrast and signal distribution were compared between treatment groups. Two commercial fluorescence imaging systems were tested for simultaneous imaging of ICG and ABY-029. RESULTS: ABY-029 has a moderate positive correlation with viable tumor (ρ = 0.2 ± 0.4), while ICG demonstrated a strong negative correlation (ρ = -0.6 ± 0.1). The contrast-to-variance ratio was highest in the ABY-029 +ICG (2.5 ± 0.8), compared to animals that received ABY-029 (2.3 ± 0.8) or ICG (2.0 ± 0.5) alone. Moreover, the combination of ABY-029 + ICG minimizes the correlation between viable tumor and fluorescence intensity (ρ = -0.1 ± 0.2) indicating the fluorescence signal distribution is more homogeneous throughout the tumor milieu. CONCLUSION: Dual-agent imaging utilizing a single channel in a commercial fluorescence-guided imaging system tailored for IRDye 800CW is a promising method to increase tumor contrast in a clinical setting.

Maintenance therapy in transplant ineligible adults with newly-diagnosed multiple myeloma: A systematic review and meta-analysis.

BACKGROUND: The role of maintenance therapy in transplant ineligible multiple myeloma (MM) patients following a period of fixed duration induction therapy remains unclear. OBJECTIVES: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) examining maintenance therapy compared to observation. METHODS: We conducted a comprehensive search including MEDLINE, Embase, and the Cochrane database up to February 28, 2020, for RCTs comparing maintenance therapy to observation in newly diagnosed transplant ineligible MM patients. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. We performed meta-analyses using a random-effects model and assessed certainty using GRADE methodology. MAIN RESULTS: We included five RCTs with a total of 1139 patients. Patients receiving maintenance therapy had improved progression-free survival (PFS) compared to observation (Hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.38 to 0.62, high certainty); however, there was no difference in overall survival (HR 0.96, 95% CI 0.76-1.2, moderate certainty). Adverse events were higher in the maintenance group compared to observation (very low to moderate certainty). CONCLUSION: Maintenance therapy increases PFS in transplant ineligible MM patients following a fixed period of induction therapy; however, this must be weighed against the increased risk of adverse events.

Geriatric Assessment and Frailty Scores Predict Mortality in Myeloma: Systematic Review and Meta-analysis.

The incidence of multiple myeloma is increasing as the proportion of older adults is growing rapidly. A critical evaluation of the evidence available is needed to guide the management of older patients with myeloma. A systematic review was conducted to report the prognostic value of geriatric assessment and frailty scores in older patients with multiple myeloma. We conducted a literature search in February and August 2018. Two researchers extracted the data and assessed the quality of the studies. Geriatric assessment and frailty scores were defined as those evaluating at least 2 geriatric domains. Main outcomes were mortality or toxicity. We estimated the pooled hazard ratios (HR) with 95% confidence intervals (CIs) using a random-effects model. We screened titles and abstracts of 1672 citations for eligibility. Seven studies were included in the qualitative analysis, of which 3 were included in the meta-analysis. Two studies reported similar risks of hematologic adverse events in intermediate-fit and in frail patients compared to frail, but a significantly increased risk of nonhematologic adverse events in frail patients compared to fit patients. In meta-analysis, a significantly increased HR for death was observed in patients with activity of daily living score ≤ 4 (pooled HR = 1.576; 95% CI, 1.051-2.102; χ2 = 0.87; P = .647; I2 = 0). Patients classified as frail showed higher risk of death than fit patients (pooled HR = 2.169; 95% CI, 1.002-2.336; χ2 = 3.02; P = .221; I2 = 33.7%). GA and frailty score are effective in predicting mortality in older adults with myeloma.

Preclinical imaging of epidermal growth factor receptor with ABY-029 in soft-tissue sarcoma for fluorescence-guided surgery and tumor detection.

BACKGROUND AND OBJECTIVES: Fluorescence-guided surgery using epidermal growth factor receptor (EGFR) targeting has been performed successfully in clinical trials using a variety of fluorescent agents. We investigate ABY-029 (anti-EGFR Affibody® molecule labeled with IRDye 800CW) compared with a small-molecule perfusion agent, IRDye 700DX carboxylate, in a panel of soft-tissue sarcomas with varying levels of EGFR expression and vascularization. METHODS: Five xenograft soft-tissue sarcoma cell lines were implanted into immunosuppressed mice. ABY-029 and IRDye 700DX were each administered at 4.98 µM. Fluorescence from in vivo and ex vivo (fresh and formalin-fixed) fixed tissues were compared. The performance of three fluorescence imaging systems was assessed for ex vivo tissues. RESULTS: ABY-029 is retained longer within tumor tissue and achieves higher tumor-to-background ratios both in vivo and ex vivo than IRDye 700DX. ABY-029 fluorescence is less susceptible to formalin fixation than IRDye 700DX, but both agents have disproportional signal loss in a variety of tissues. The Pearl Impulse provides the highest contrast-to-noise ratio, but all systems have individual advantages. CONCLUSIONS: ABY-029 demonstrates promise to assist in wide local excision of soft-tissue sarcomas. Further clinical evaluation of in situ or freshly excised ex vivo tissues using fluorescence imaging systems is warranted.

Development of a Medicare Health Outcomes Survey Deficit-Accumulation Frailty Index and Its Application to Older Patients With Newly Diagnosed Multiple Myeloma.

Purpose: To develop a frailty index using the Rockwood Accumulation of Deficits approach for the Medicare Health Outcomes Survey (MHOS) and apply it in a subset of older patients with newly diagnosed multiple myeloma. Methods: Data from 2,692,361 patients without cancer, > 66 years of age, in SEER-MHOS linked databases between 1998 and 2009 were analyzed. A frailty index was constructed, resulting in a 25-item scale; cutoff values were created for individuals classified as frail. This frailty index was then applied to 305 patients with newly diagnosed myeloma in the database to predict overall survival. Results: In the derivation cohort of patients without cancer, the median age was 74 years and the mean frailty index was 0.23 (standard deviation, 0.17). Among patients without cancer, each 10% increase in frailty index (approximately three to four more deficits) was associated with a 40% increased risk for death (adjusted hazard ratio, 1.397; 95% CI, 1.396 to 1.399; P < .001). In the cohort of patients with newly diagnosed myeloma, the median age was 76 years an d the mean frailty index was 0.28 (standard deviation, 0.17). Each 10% increase in frailty index was associated with a 16% increased risk for death (adjusted hazard ratio, 1.159; 95% CI, 1.080 to 1.244; P < .001). Fifty-three percent of patients with multiple myeloma were considered frail. The estimated median overall survival of patients considered frail was 26.8 months, compared with 43.7 months (P = .015) for those who were not. Conclusion: The MHOS-based frailty index was prognostic for patients with multiple myeloma in predicting overall survival.

Novel Treatments for Multiple Myeloma: What Role Do They Have in Older Adults?

Multiple myeloma is a malignant plasma cell disease, which typically affects older patients, with a median age at diagnosis of 70 years. The recent introduction of novel drugs and ongoing improvements in supportive care have significantly contributed to overall better management and outcomes for patients with multiple myeloma. Autologous stem-cell transplantation has been a standard part of therapy for myeloma patients for many years, first in younger patients and increasingly in older, and may still be considered in selected older patients with myeloma. In addition, in both newly diagnosed patients and in the relapsed/refractory setting, a number of novel agents tested in large phase III trials have yielded improvements in overall outcomes. As clinical trials under-enrol older patients and have stringent exclusion criteria, the data and results from them may not be generalizable to all older adults. In this review, we examine the treatment options for older adults with myeloma with a specific focus on the currently available data on novel agents in this cohort. The clinical efficacy and unique toxicity profile of each novel agent must be considered prior to the treatment plan in older adults.