Therapeutics

Background/Objectives: Our objective was to describe the safety and efficacy of enteral droxidopa, a norepinephrine prodrug, for intravenous (IV) vasopressor weaning in intensive care unit (ICU) patients. Methods: This was a single-center, retrospective descriptive study of adult ICU patients. Patients who received ≥ 4 consecutive doses of droxidopa for IV vasopressor weaning were included. The cessation of the IV vasopressor without re-initiation within 72 h of droxidopa initiation was the primary outcome. The adverse events assessed included hypotension, hypertension, and arrhythmias. Results: Forty-six patients were included, with a median age of 61. Forty-two patients (91%) were on midodrine at the time of droxidopa initiation. The median daily midodrine dose was 80 mg. The median time from ICU admission to droxidopa initiation was 17 days. Patients were on a median of one IV vasopressor at the time of droxidopa initiation, with norepinephrine as the most common agent (50%). The median initial daily droxidopa dose was 300 mg, with a median maximum daily dose of 900 mg. Vasopressor support was discontinued within 72 h of droxidopa initiation in 46% of patients, with a median time to IV vasopressor cessation of 3.3 days. There were no incidences of hypotension, hypertension, arrhythmias, or ICU readmissions related to droxidopa. Droxidopa was continued upon discharge in 29% of patients. Conclusions: Droxidopa may be a safe and effective option to facilitate the weaning of IV vasopressor support in patients who are refractory or intolerant to midodrine. Larger prospective studies are needed to confirm these findings. Full article

Background: Psoriasis has a huge impact on a patient’s life. Treatment dissatisfaction and non-adherence are common among patients with psoriasis, partly due to discordance between individual preferences and recommended treatments. The modern strategy for psoriasis should be focused on human-centric treatment that recognizes the needs and preferences of patients with a goal for safe, effective, quality and acceptable health services for a lifetime. The aim of this analysis was to capture patients’ preferences with moderate-to-severe psoriasis regarding various treatment attributes. Methods: A specialized questionnaire containing four attributes with three levels, each, was used, followed by an orthogonal plan based on conjoint analysis. Nine combinations of therapeutic scenarios were produced as a result, to investigate participants’ preferences. Respondents were asked to rank alternatives from best to worst. Results: The risk of developing pneumonia or other serious infections within a decade seems to be higher in patients with an implied assigned value of 37. The second attribute was the type and frequency of the administration with a value of 27, followed by the treatment effectiveness with great improvement of body surface with a value of 25. The lowest utility (11) was the sustainability of early remission of psoriasis. Conclusions: Psoriasis patients want safe, effective and easy to administer treatments. Full article

Hematopoietic stem cell (HSC) therapy remains essential in treating blood disorders, autoimmune diseases, neurodegenerative conditions, and cancers. Despite its potential, challenges arise from the inherent heterogeneity of HSCs and the complexity of their regulatory niche. Recent advancements in single-cell RNA sequencing and chromatin accessibility sequencing have provided deeper insights into HSC markers and chromatin dynamics, highlighting the intricate balance between intrinsic and extrinsic regulatory mechanisms. Zebrafish models have emerged as valuable tools in HSC research, particularly through live imaging and cellular barcoding techniques. These models have allowed us to describe critical interactions between HSCs and embryonic macrophages, involving reactive oxygen species and calreticulin signaling. These are essential for ensuring HSC quality and proper differentiation, with implications for improving HSC transplant outcomes. Furthermore, the review examines clonal hematopoiesis, with a focus on mutations in epigenetic regulators such as DNMT3A, TET2, and ASXL1, which elevate the risk of myelodysplastic syndromes and acute myeloid leukemia. Emerging technologies, including in vivo cellular barcoding and CRISPR-Cas9 gene editing, are being investigated to enhance clonal diversity and target specific mutations, offering potential strategies to mitigate these risks. Additionally, macrophages play a pivotal role in maintaining HSC clonality and ensuring niche localization. Interactions mediated by factors such as VCAM-1 and CXCL12/CXCR4 signaling are crucial for HSC homing and the stress response, opening new therapeutic avenues for enhancing HSC transplantation success and addressing clonal hematopoiesis. This review synthesizes findings from zebrafish models, cutting-edge sequencing technologies, and novel therapeutic strategies, offering a comprehensive framework for advancing HSC biology and improving clinical outcomes in stem cell therapy and the treatment of hematologic diseases. Full article

Background/Objectives: Cytomegalovirus (CMV) infection is a frequent complication after lung transplantation, especially in high-risk donor-positive/recipient-negative (D+/R−) patients. CMV-specific hyperimmunoglobulin (CMV-HIG), administered either with antivirals or as monotherapy, may be beneficial for preventing or treating CMV infection in selected clinical scenarios. This study evaluated CMV-HIG indications and their impact on clinical outcomes in our lung transplant unit. Methods: We retrospectively analyzed adult lung transplant recipients (2010–2023) who received ≥2 doses of CMV-HIG for universal prophylaxis, monotherapy prophylaxis, preemptive therapy, or treatment of invasive disease. Results: CMV-HIG was administered to 204 out of 336 recipients (61%). CMV-HIG was well tolerated, with no treatment-related adverse events. Indications were preemptive therapy (63%), universal prophylaxis (24%), monotherapy prophylaxis (7%), and treatment of invasive disease (6%). CMV-HIG was well tolerated, with no treatment-related adverse events. No patients developed invasive disease during combination prophylaxis or preemptive treatment. The combination treatment of patients with invasive disease was also effective, and no cases of VGC resistance were detected. CMV-HIG monoprophylaxis has allowed us to delay or prevent viral replication in recipients who developed VGC side effects. Rates of acute rejection, Chronic Lung Allograft Dysfunction (CLAD), and overall survival were similar across CMV risk groups. Conclusions: Our results showed that the combined use of CMV-HIG and antiviral agents is effective in preventing CMV infection and disease in high-risk lung transplant recipients. This combination is also useful in treating invasive disease and preventing VGC resistance. Additionally, CMV-HIG monoprohylaxis can delay or prevent viral replication in recipients experiencing VGC-related side effects. These findings support the use of CMV-HIG in selected clinical settings, although prospective studies are needed to define its potential benefits within the current therapeutic armamentarium. Full article

Background/Objectives: Biochemical recurrence (BCR) occurs in 15–40% of men within five years of radical prostatectomy (RP), presenting a major challenge for long-term disease control. While salvage radiotherapy (SRT) and androgen deprivation therapy (ADT) are established post-RP interventions, the optimal integration of ADT with SRT—regarding timing, duration, and patient selection—remains unclear. We aimed to synthesize current clinical evidence on the efficacy and safety of combining ADT with SRT in patients experiencing BCR after RP. Methods: A narrative review was conducted, encompassing retrospective cohort studies, prospective randomized controlled trials (notably RTOG 9601, GETUG-AFU 16, RADICALS-HD, and SPPORT), and meta-analyses. Studies were selected based on relevance to combined ADT + SRT versus SRT alone, with outcomes of interest including biochemical progression-free survival (bPFS), metastasis-free survival (MFS), and overall survival (OS). Trial characteristics, ADT duration (short-term [4–6 months] versus long-term [≥24 months]), radiation scheme, and prostate specific antigen (PSA) thresholds at SRT initiation were extracted and compared. Results: The combination of ADT and SRT represents a promising strategy for the treatment of prostate cancer with BCR after RP. Current evidence supports its benefit in terms of disease control and survival, particularly in high-risk patients. Conclusions: Differences in inclusion criteria, ADT duration, and the heterogeneous quality of the available studies limit the formulation of universal recommendations. Well-designed prospective trials are needed to optimize therapeutic approaches and personalize treatment based on each patient’s risk profile. Full article

Background: The outgrowth of castration-resistant prostate cancer (CRPC) dictates patient morbidity and mortality. Recurrence of prostate cancer (PC) following androgen-deprivation therapy (ADT) often occurs due to constitutively active androgen receptor (AR) splice variants (AR-Vs), primarily AR-V7. Therefore, safe and effective therapies enabling the suppression of both full-length AR (AR-FL) and AR-Vs are urgently needed. The natural compound dimethyl sulfoxide (DMSO) has negligible cytotoxicity at concentrations below 5% and has anticancer potential. DMSO has been broadly used in biomedical research as a solvent for pharmaceuticals, as a cryoprotectant for cells, and as a topical treatment to suppress pain and inflammation. We investigated the effect of low-dose DMSO on AR expression, cell viability, and metastatic ability in PC cell lines expressing both AR-FL and AR-V7 (e.g., 22Rv1) and those expressing only AR-FL (e.g., C4-2B). Methods: MTT cell viability assays were performed to measure DMSO-induced cytotoxicity. Wound-healing assays were conducted to monitor the effect of DMSO on the migratory phenotype of cancer cells. Western blot analyses were performed to study the efficacy of DMSO in suppressing the protein levels of AR-FL and AR-V7, and expression of heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) was measured as a possible mechanism. Results: At concentrations of 0.1–1% (v/v), DMSO treatment showed minimal cytotoxicity, whereas the highest concentration used (2.5%) showed approximately 20% cytotoxicity at 96 h. Interestingly, however, DMSO treatment at concentrations of 1.0 and 2.5% significantly inhibited the migration of PC cells. Treatment with DMSO led to a dose-dependent inhibition of both AR-FL and AR-V7. Notably, in 22Rv1 cells, DMSO potently downregulated the expression of hnRNPH1, a splicing factor often associated with AR expression and signaling. Conclusions: Our findings suggest that low concentrations of DMSO may have potential as an effective anticancer agent, both at the initial and later stages when PC cells become castration resistant. Full article

Background/Objectives: Gender-affirming surgery (GAS) is associated with improved mental health outcomes in transgender and gender-diverse (TGD) individuals. However, TGD populations experience disproportionately high rates of substance use disorders (SUDs), which are established risk factors for surgical complications. Despite this, the relationship between preoperative SUDs and postoperative outcomes following GAS has not been studied. Our objective was to evaluate how specific SUD subtypes, including tobacco, alcohol, and cannabis, impact short- and medium-term postoperative complications following GAS. Methods: A retrospective cohort study was conducted using the TriNetX Research Network, which includes de-identified electronic health records from over 100 million U.S. patients. Adults with documented gender dysphoria who underwent GAS between April 2015 and April 2025 were included. Patients were divided into four groups: no SUD, tobacco use, alcohol use, and cannabis use. Propensity score matching was used to control for demographic variables. Postoperative complications were assessed at 30 days and 6 months. Results: Alcohol use was significantly associated with increased rates of delayed wound healing, wound dehiscence, gastrointestinal symptoms, and postoperative pain at both 30 days and 6 months. Cannabis use was linked to higher rates of wound dehiscence, infections, GI symptoms, and pain. Tobacco use showed the broadest impact, significantly associated with nearly all complications measured except pain at 30 days. These associations persisted at six months. Conclusions: This is the first study to quantify the relationship between substance use and GAS outcomes. Preoperative use of tobacco, alcohol, and cannabis was independently associated with increased postoperative complications. These findings underscore the need for systematic preoperative screening and the development of SUD-specific perioperative care pathways to improve outcomes and advance equity in surgical care for TGD patients. Full article

Background: Multiple Chemical Sensitivity (MCS) is a complex, disabling condition marked by non-specific symptoms in response to low-level chemical exposures. It often leads to substantial impairments in quality of life, psychological health, and daily functioning. Although non-pharmacological approaches—such as lifestyle and psychological interventions—are widely used, their clinical effectiveness remains unclear. Objective: We aim to evaluate the effectiveness of lifestyle-based approaches in improving clinical and psychosocial outcomes in adults with Multiple Chemical Sensitivity. Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251013537). Literature searches were carried out in MEDLINE (PubMed), CINAHL, Google Scholar, and ResearchGate between March and April 2025. Eligible studies included adults (≥18 years) with a confirmed diagnosis of MCS and reported outcomes such as perceived stress, anxiety, depressive symptoms, or quality of life. Methodological quality and risk of bias were independently assessed using the PEDro scale, NIH Quality Assessment Tool, CEBMa checklist, and Cochrane RoB 2.0. Results: Twelve studies (N = 378) met the inclusion criteria. Cognitive and behavioral therapies demonstrated the most consistent evidence of efficacy, with reductions in symptom severity, maladaptive cognitive patterns, and functional limitations. Mindfulness-based stress reduction showed favorable outcomes, while other mindfulness-based interventions yielded mixed results. Exposure-based therapies contributed to increased chemical tolerance and reduced avoidance behavior. Electromagnetic and biomedical approaches demonstrated preliminary but limited effectiveness. Aromatherapy was well tolerated and perceived as relaxing, though its clinical impact was modest. Conclusions: Cognitive and behavioral therapies appear to be most effective among lifestyle-based interventions for MCS/IEI. However, study heterogeneity limits the generalizability of findings, underscoring the need for more rigorous research. Full article

Background and Aims: Gastroesophageal reflux disease (GERD) is the most common esophageal disorder worldwide and a progressive condition leading to Barrett’s esophagus and adenocarcinoma. Continuous medical therapy with proton pump inhibitors fails to restore the antireflux barrier and is unable to relieve symptoms in up to 40% of patients. A tailored and standardized antireflux surgical procedure may increase cure rates and meet patient expectations. Methods and Results: Antireflux surgery aims to reestablish the natural antireflux barrier, which includes the diaphragmatic crura, the lower esophageal sphincter (LES), and the angle of His along with the gastroesophageal flap valve. For decades, the Nissen total fundoplication has been the primary procedure and remains the gold standard for surgical treatment. Alternatives such as Toupet partial fundoplication, Dor partial fundoplication, and the magnetic sphincter augmentation (LINX™) procedure have been developed to mitigate side effects like dysphagia, gas-bloat syndrome, and the inability to belch or vomit. Recent clinical findings regarding a novel procedure, RefluxStop™, indicate that restoring the gastroesophageal flap valve, in conjunction with anterior fundoplication and a silicone device for stabilizing the LES beneath the diaphragm, can achieve lasting reflux control and enhance patient-reported outcomes. Conclusions: The planning of healthcare services and actionable strategies to improve equity and quality of treatment is critical to address the global burden of GERD. Modern laparoscopic surgery for GERD is safe and effective and should be performed in centers offering a complete diagnostic pathway and specific surgical techniques tailored to the individual GERD phenotype. Shared decision-making between the surgeon and the patient is essential for the choice of operation. A personalized approach can offer clinical benefits over total fundoplication and improve patient-reported outcomes. Full article

Background: Human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) allow for high-throughput evaluation of cardiomyocyte (CM) physiology in health and disease. While multimodality testing provides a large breadth of information related to electrophysiology, contractility, and intracellular signaling in small populations of iPSC-CMs, current technologies for analyzing these parameters are expensive and resource-intensive. Methods: We have designed a novel 2D/3D hybrid organoid system that can harness optical imaging techniques to assess electromechanical properties and calcium dynamics across CMs in a high-throughput manner. We validated our methods using a doxorubicin-based system, as the drug has well-characterized cardiotoxic, pro-arrhythmic effects. Results: This novel hybrid system provides the functional benefit of 3D organoids while minimizing optical interference from multilayered cellular systems through our cell-culture techniques that propagate organoids outwards into 2D iPSC-CM sheets. The organoids recapitulate contractile forces that are more robust in 3D structures and connectivity, while 2D CMs facilitate analysis at an individual cellular level, which recreated numerous doxorubicin-induced electrophysiologic and propagation abnormalities. Conclusions: Thus, we have developed a novel 2D/3D hybrid organoid model that employs an integrated optical analysis platform to provide a reliable high-throughput method for studying cardiotoxicity, providing valuable data on calcium, contractility, and signal propagation. Full article

Animal models are indispensable in biomedical research, offering critical insights into disease mechanisms and therapeutic strategies. However, existing models often inadequately replicate human pathophysiology, leading to discrepancies between preclinical and clinical outcomes. Despite their contributions, many models exhibit significant limitations, especially concerning cancer and infectious diseases. Inaccurate modeling of human biological responses can result in failed clinical trials, escalated research costs, and delays in developing effective treatments. The golden hamster (Mesocricetus auratus) has emerged as a viable model, particularly in cancer and infectious disease research. Sharing physiological and immunological profiles similar to humans, the golden hamster offers distinct advantages over other rodent models, such as mice and rats. This review explores the benefits of using golden hamsters in cancer research, highlighting their contributions to scientific advancements while also addressing the limitations due to incomplete immunological and molecular knowledge about this species. Full article

Background: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are chronic conditions often accompanied by a prothrombotic state. Antifibrotic therapies, including nintedanib and pirfenidone, have demonstrated efficacy in slowing disease progression. Despite the known interactions between coagulation pathways and fibrotic processes, there is a lack of data in the literature on the safety of the concomitant use of anticoagulants and antifibrotics. Objectives: This study aimed to evaluate the safety and clinical impact of combining antifibrotics and anticoagulants in patients with IPF or PPF. A single-center, retrospective study was conducted on 137 patients diagnosed with IPF or PPF, 25 of whom were on concurrent anticoagulant therapy (AC+). Baseline demographics, pulmonary function tests (PFTs), bleeding risk scores (HAS-BLED, RIETE), and clinical outcomes were analyzed over a 12-month follow-up period. Methods: Statistical analyses included t-tests, χ² tests, Kaplan–Meier survival analysis, and multivariate logistic regression. Results: Two clinically relevant bleeding events were observed, with one in the AC+ group. No major bleeding episodes occurred in either group. Baseline forced vital capacity (FVC) was lower in the AC+ group (73.4 ± 16.9% vs. 83.0 ± 21.9%; p = 0.04), but no significant differences were observed in FVC, forced expiratory volume (FEV1), or diffusing capacity for carbon monoxide (DLCO) at 6 and 12 months. Survival rates and radiological progression were comparable between groups. Multivariate analysis revealed that DLCO was an independent predictor of mortality (HR 0.84; p = 0.005), while anticoagulant use was not. Conclusions: The concomitant use of antifibrotics and anticoagulants appears safe, with no significant increase in bleeding risk or adverse effects on disease progression. Future prospective studies are required to confirm these findings and explore the long-term impact of this therapeutic combination. Full article

Venous thromboembolic events (VTEs), especially in the form of portal vein thrombosis (PVT), are common complications of cirrhosis and are associated with significant morbidity. These patients can also be easily tipped toward bleeding because of deficiencies in procoagulant factors and pharmacokinetic and pharmacodynamic changes that occur during disease progression. Therefore, the understanding of how to use pharmacotherapy to treat VTE is a key to success in achieving VTE resolution without potentiating adverse bleeding events (AEs). Based on a review of the literature and the authors’ clinical experience, it was determined that unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, argatroban, warfarin, and direct oral anticoagulants all have evidence of use in patients with cirrhosis and VTE. However, the available literature is mostly limited to retrospective studies and case reports. There appears to be a paucity of prospective, randomized trials that compare the available pharmacotherapy at typical and adjusted doses. Overall, the decision as to the choice of agent and dose prescribed for anticoagulant therapy should include assessment on clot burden, bleeding risk, drug-drug/disease interactions, and the risk of presence of AEs. Full article

Background: In metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation, osimertinib is the cornerstone treatment able to prolong overall survival (OS). Evidence around osimertinib being effective in leptomeningeal metastasis (LM) is scarce. Methods: We conducted a retrospective cohort study of patients with metastatic NSCLC-EGFR mutation treated with osimertinib at Sunnybrook Hospital. Results: We identified a total of 56 patients. Of these, 45 (79.4%) were never smokers, 53 (94.6%) had adenocarcinoma histology, and 26 (46.42%) had either the EGFR exon 21-L858R mutation or exon 19 deletion. The estimated median OS was 51 months (43.5–58.5). All eight patients with LM died during the study period. From the time of NSCLC diagnosis, the OS of patients without LM was 53 months (95% CI 47.2–58.7), and with LM was 21 months (95% CI 3.0–39), p = 0.001. However, the median OS from LM diagnosis was 2 months (95% CI, 1.0–26). Conclusions: In our population of patients with metastatic NSCLC-EGFR mutation who received osimertinib, there was a significant reduction in life expectancy in the group with LM. Patients who had advanced stage at diagnosis and were more likely to develop LM exhibited poorer survival compared to those who had early-stage cancer at diagnosis and developed metastases later on. Full article

Background/Objectives: The epigenetic drug 5-azacytidine (AzaC) is being used for the treatment of myeloproliferative diseases. It has multiple immunomodulating activities: it enhances the activity of Treg cells and suppresses effector T cell proliferation and function. Our aim was to repurpose AzaC for the treatment of multiple sclerosis (MS). AzaC treatment of myelodysplastic syndrome often improves the autoimmune disorders accompanying it. Another epigenetic drug, decytabin, was effective in EAE, suggesting that AzaC might behave similarly. Earlier, we found that AzaC improves aggrecan-induced arthritis in mice, further supporting our hypothesis. Methods: AzaC was tested in an animal model of MS: MOG_35–55-induced experimental allergic encephalomyelitis (EAE) in B6 mice. In addition to AzaC, its ester, prodrug triacetyl-5-azacytidine (TAC), reported earlier to exhibit improved stability and oral bioavailability, was also tested. Results: In our proof-of-concept experiment, i.p. administered AzaC ameliorated EAE. Then, we demonstrated that oral TAC is as effective as the positive comparator fingolimod. Next, we demonstrated that sub-optimal doses of oral TAC and fingolimod positively synergize. Importantly, the myelosuppression induced by TAC was not worse than that of the gold-standard fingolimod. Conclusions: Ours is the first study reporting the therapeutic activity of oral TAC. Both AzaC and TAC were effective in EAE; therefore, they can be proposed for the treatment of remitting–relapsing MS and possibly other autoimmune diseases. In addition, combination treatment with TAC and fingolimod might allow for lower individual drug doses, thus offering an alternative when side effects limit the use of current multiple sclerosis drugs. Full article

Plant extracts are increasingly becoming an answer to expensive, high-dose, synthesized chemotherapy, with milder side effects and easier accessibility. Many botanical plants contain active ingredients, such as terpenoids and alkaloids, which may combat cancer; however, studies need to be performed to test whether they are solely effective enough and whether the extracted compounds are selective for the tumor itself. Many chemotherapy drugs were initially of botanical origin, such as vincristine from Catharanthus roseus and paclitaxel from the Taxus baccata tree. The objective of this review is to assess the mechanisms of herbal therapeutics in their role against malignancy. Ajwa, curcumin, ginseng, lycopene, and ursolic acid were all respectively evaluated in the paper for their prevalent properties, their method of extraction, notable usage in medicine, which pathways they activate, and whether the transductions can disrupt cancer formation or proliferation. The findings from the review demonstrated that all the therapeutics exhibited pro-apoptotic behavior, Ajwa and curcumin exerted cell cycle arrest upon neoplasms, and Ajwa, curcumin, and lycopene showed anti-metastatic behavior. Most extracts were tested on colorectal cancer, and the pathways most commonly applied were through BAX/Bcl2 and endoproteases, such as caspase-3 and caspase-9, indicating predominantly mitochondrial apoptosis. In addition, cell cycle arrest was noted to occur during the G2/M phase via Wnt/β-catenin in both curcumin and ginseng, independently of the Wnt/β-catenin pathway in Ajwa constituents, reducing cell viability. All of these studies were demonstrated in vitro within varieties of single cell cultures, which did not take into account bioavailability nor properly demonstrate the tumor microenvironment, which may not yield the same results in vivo. Clinical trials need to be undergone to appropriately test effective dosages, as if a compound is strongly pro-apoptotic, it may not be selective just to tumor cells but also to healthy cells, which may impair their functions. Full article

Background: Handgrip strength (HGS) is strongly recommended for use in clinical settings because it is a convenient assessment of muscle strength and a robust prognostic indicator of health. However, it may lack use in clinical settings, and may not be well understood by healthcare providers and patients. We sought to determine the healthcare provider and patient perceptions of HGS in an internal medicine resident clinic. Methods: Healthcare providers were presented with didactic sessions for HGS and engaged in routine follow-up meetings. HGS was measured on eligible older adult patients during an approximately 9-month phased study period. Both healthcare providers and patients were asked to complete a questionnaire with 10-point Likert scale response items regarding their experiences with HGS. Results were presented as descriptive. Results: Overall, patients had a positive perception of HGS, as they understood HGS instructions (score: 9.8 ± 0.7), their results (score: 9.5 ± 1.3), and found value in HGS for their health (score: 8.4 ± 2.3). However, healthcare providers were generally neutral about HGS, such that at study end HGS was viewed as moderately valuable for their practice (score: 6.0 ± 2.1) and patients (score: 6.0 ± 2.1). Conclusions: Overall, patients had a positive perception of HGS, but healthcare providers were neutral. Our findings should be used to guide HGS for possible implementation and quality management in appropriate healthcare settings. Full article

Background/Objectives: This scoping review aims to identify the diverse existing tools applicable for the measurement of SUD outcomes, examining and comparing their item characteristics, benefits, limitations, cost effectiveness, and overall utility. This study provides recommendations on the next steps toward the design and dissemination of a unified version of a standard SUD outcome measurement tool. Methods: Using PRISMA-ScR guidelines, the databases PubMed and Embase, as well as the grey literature, were searched for existing SUD outcome measurement tools. Additionally, references and information on tools were found via the Addictions Drug and Alcohol Institute Library at the University of Washington. Tools were examined based on their characteristics, benefits, limitations, and overall utility. Results: Thirteen tools met the analysis requirements and were analyzed, revealing great variance. The domains covered by each tool is categorized for comparison among other tools, showing strong focus over some domains more than others. Additionally, great variance in characteristics such as the number of questions, question structure, time required for completion, and scoring were seen. Sources for each of these tools’ development were seen to reveal the unique origination of each, as well as their intended utility. Conclusions: Our analysis highlights the importance of considering certain characteristics when selecting measurement instruments, emphasizing the need for clear and concise questions to enhance levels of adherence and interpretation. The current lack of standardization among SUD measurement tools in assessing new and existing SUD treatment modalities has hindered progress in the field, compromising the quality of care delivered. Full article

Background: Plasma cell myeloma is an incurable malignancy of clonal plasma cells. Recent success in immunotherapeutic strategies has altered the landscape of myeloma treatment. Daratumumab is an anti-CD38 IgG kappa monoclonal antibody that has shown great efficacy in the treatment of myeloma. However, Daratumumab brought with it new challenges in post-therapeutic laboratory assessment, including therapeutic antibody interference with serum protein electrophoresis and serum immunofixation electrophoresis assays. In this study, we highlight the interference identified in post-therapeutic flow cytometry analysis related to bound Daratumumab on normal hematopoietic cells. We also highlight the methods of detection of residual plasma cell neoplasm, post-Daratumumab therapy.: A total of 28 patients with refractory plasma cell myeloma who received Daratumumab (2016–2018) were included in this study. Flow cytometry was performed using 4- or 10-color antibody panels (BD FASC Canto) and analyzed by cluster analysis (Cytopaint Classic software) using four tube panels including VS38c for measurable residual disease (MRD) testing. Pretreatment and post-Daratumumab follow-up bone marrow flow cytometry samples were analyzed. In addition, 10 multiple myeloma patient samples were reflexed to multi-epitope CD38 analysis by flow cytometric analysis of post-Daratumumab residual disease. When discussing CD38 expression, we will refer to CD38 as being detected by conventional reagents. Results: All post-Daratumumab-treated cases (100%) showed negative staining for CD38 using conventional reagents on all plasma cells in the specimens. MRD testing successfully identified small clonal plasma cell populations using VS38C and multi-epitope CD38 (meCD38) antibodies, despite the absence of demonstrable CD38 expression. Additionally, all cases exhibited weak kappa light chain staining on hematogones, attributed to the binding of Daratumumab kappa monoclonal antibody. This interaction can create the appearance of a CD10+ monotypic B-cell population. We also noted diminished CD38 staining on myeloblasts, resulting in an atypical CD34/CD38 staining pattern. This alteration could potentially be misinterpreted as indicative of a myelodysplastic neoplasm (MDS). Furthermore, decreased staining of CD38 was noted on T cells, natural killer (NK) cells, basophils, monocytes, and plasmacytoid dendritic cells. Conclusions: With the emergence of successfully targeted immunotherapies, such as anti-CD38 antibodies, it is important to understand and correctly interpret variations in flow cytometry that may arise from the therapy. Hematogones exhibit high-intensity levels of CD38 expression; thus, Daratumumab binds to them, creating the appearance of kappa expression on all hematogones. Stage I/early stage II hematogones normally lack surface immunoglobulin light chain expression, but in the presence of Daratumumab, they appear to be a CD10(+) monotypic population of B cells. The misinterpretation of these normal cells as a CD10(+) B-cell clone can lead to inaccurate assessment, unnecessary bone marrow immunohistochemical evaluation, and unwarranted anxiety. Additionally, artefacts on various other hematopoietic cells can result in inaccurate assessments of immunophenotypic aberrancy due to binding of the drug. This may lead to the false interpretation of a secondary/therapy-related myeloid neoplasm. This study highlights in detail the interferences that must be considered when assessing residual disease in the era of targeted drug therapies. Full article