Therapeutics, Volume 2, Issue 1 (March 2025) – 5 articles

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

Background: Past studies have found mixed benefits to treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in heart failure (HF) patients. Here we evaluate the effect of OSA treatment in symptomatic HF patients who received an inpatient sleep study. Methods: We performed a retrospective observational review of 6-month outcomes in 109 hospitalized HF patients with newly diagnosed OSA who followed up to initiate PAP therapy (N = 48) or never started PAP (N = 61). Primary outcomes were cardiovascular readmissions and all-cause mortality. Results: Patients who started PAP overall had worse apnea–hypopnea index (AHI) compared to those who did not (AHI 49.4 vs. 31.3). There were significantly fewer deaths in the “PAP” group versus the “non-PAP” group: 2% versus 15% (p = 0.04). We then sub-analyzed our population based on strict CPAP adherence, defined as ≥4 PAP hours per night and at least ≥70% of nights used. Twenty-eight out of 48 PAP patients met adherence criteria. The “Adherent” group (N = 28) had notable PAP use of 6.3 h per night (interquartile range 5–7.7 h/night). In comparison to the “Non-Adherent or Never Started PAP” group (N = 81), the Adherent group had no observed deaths and significantly fewer first-time readmissions: 11% versus 33% (p = 0.026). Conclusions: Despite worse baseline OSA in our PAP population, we found an association between PAP compliance and improved cardiovascular outcomes. Future research should investigate dose–response relationships between PAP use and HF outcomes. There are important limitations to our study. Full article