Acute leukemia with KMT2A rearrangement: A master of disguise.

Mixed-phenotype acute leukemia (MPAL) is a rare form of leukemia with ambiguous lineage, and there are challenges in accurately diagnosing this entity according to formal criteria. Here we report a case which was initially diagnosed as "AML" based on atypical peripheral blood flow cytometry that was subsequently determined to be B-ALL with KMT2A rearrangement based on marrow results. Although KMT2A rearrangements represent a defining genetic abnormality for acute leukemia of ambiguous lineage, this case did not meet the criteria for MPAL based on WHO 2022 criteria. This case highlights the diagnostic challenges of MPAL and the potential limitations of the current classification. We discuss the most appropriate workup and management of these patients and identify areas for future study.

Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease. ESR1 mutations have been identified as a common mechanism of endocrine therapy resistance in ER+ breast cancer. The first-generation selective estrogen receptor degrader (SERD) fulvestrant has shown some activity against ESR1 mutant tumors. However, due to its poor bioavailability and need for intramuscular injection, it may not be the optimal therapy for patients. Second-generation SERDs were developed to overcome these limitations. These newer drugs have improved oral bioavailability and pharmacokinetics, making them more convenient and effective for patients. Several oral SERDs are now in phase III trials for early and advanced ER+ breast cancer. This review summarizes the background of oral SERD development, the current status, and future perspectives.

Effect of osteopathic manipulative treatment and Bio-Electro-Magnetic Energy Regulation (BEMER) therapy on generalized musculoskeletal neck pain in adults.

CONTEXT: General neck pain is a prevalent complaint made by patients to their physicians and is often of a suspected musculoskeletal origin. Osteopathic manipulative treatment (OMT) is a form of manual therapy utilized by osteopathic physicians and some allopathic physicians to treat a broad variety of musculoskeletal ailments, including neck pain. Bio-Electro-Magnetic Energy Regulation (BEMER) is an emerging therapeutic modality that deploys a biorhythmically defined stimulus through a pulsed electromagnetic field and has been shown to reduce musculoskeletal pain. Studies on these treatments have independently yielded promising results. Therefore, it is possible that the utility of OMT and BEMER can produce an additive improvement in the treatment of neck pain. OBJECTIVES: The objectives of this study are to investigate the individual and combined effects of OMT and BEMER therapy on neck pain in adults. METHODS: Adults with nonspecific neck pain were recruited for the study. A total of 44 participants met the study inclusion criteria and were randomized into one of four study groups: OMT-only, BEMER-only, OMT+BEMER, or CONTROL (light touch and sham). Forty subjects completed the study, and data for 38 participants were included in our analyses. An OMT and BEMER protocol were specifically designed for this study under the guidance of a licensed osteopathic physician. Participants underwent intervention for a duration of 3 weeks. Data were obtained through baseline and postintervention assessments utilizing three surveys: Neck Disability Index (NDI), Visual Analog Scale (VAS), and Short Form 12-item Health Survey (SF-12, divided into Mental and Physical). One-way analysis of variance (ANOVA) analysis was performed retrospectively on pre- and postintervention absolute means between study groups. Significance was set at p<0.05. RESULTS: One-way ANOVA analysis demonstrated a statistically significant difference in pre- vs. postintervention mean scores between BEMER and CONTROL (p<0.05), BEMER compared to OMT (p<0.005), and BEMER compared to BEMER+OMT (p<0.05), in the NDI. The OMT+BEMER group reported an average reduction in pain on the VAS of 21.3 (±29.3) points, or a 65.0 % reduction of pain. A similarly substantial decrease in pain was reported in the BEMER study group, which showed a 46.2 % reduction in pain from baseline. The OMT and CONTROL study groups only reported a 2.9 and 23.9 % decrease, respectively. The BEMER and OMT+BEMER study groups also demonstrated a reduction in subjective reporting on the NDI, by 53.8 and 26.3 %, respectively. The BEMER study group also achieved the most substantial improvement in mental and physical well-being as reported by the SF-12. CONCLUSIONS: Study arms that incorporated BEMER yielded improvements on the NDI, VAS, and SF-12, indicating benefits to BEMER regarding improved overall functionality in routine daily activities as well as a reduction in nonspecific neck pain. Perceived pain, as demonstrated on the VAS, was seemingly improved in an additive fashion from the BEMER group to the OMT+BEMER group, although the results did not achieve statistical significance. Further study with greater participation could provide additional insight.

Efficacy and safety of cardioprotective drugs in chemotherapy-induced cardiotoxicity: an updated systematic review & network meta-analysis.

BACKGROUND: Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or precluding chemotherapy entirely. Prior studies have suggested that using common cardioprotective agents may attenuate chemotherapy-induced cardiotoxicity. However, small sample sizes and conflicting outcomes have limited the clinical significance of these results. HYPOTHESIS: A comprehensive network meta-analysis using updated and high-quality data can provide more conclusive information to assess which drug or drug class has the most significant effect in the management of chemotherapy-induced cardiotoxicity. METHODS: We performed a literature search for randomized controlled trials (RCTs) investigating the effects of cardioprotective agents in patients with chemotherapy-induced cardiotoxicity. We used established analytical tools (netmeta package in RStudio) and data extraction formats to analyze the outcome data. To obviate systematic bias in the selection and interpretation of RCTs, we employed the validated Cochrane risk-of-bias tools. Agents included were statins, aldosterone receptor antagonists (MRAs), ACEIs, ARBs, and beta-blockers. Outcomes examined were improvement in clinical and laboratory parameters of cardiac function including a decreased reduction in left ventricular ejection fraction (LVEF), clinical HF, troponin-I, and B-natriuretic peptide levels. RESULTS: Our study included 33 RCTs including a total of 3,285 patients. Compared to control groups, spironolactone therapy was associated with the greatest LVEF improvement (Mean difference (MD) = 12.80, [7.90; 17.70]), followed by enalapril (MD = 7.62, [5.31; 9.94]), nebivolol (MD = 7.30, [2.39; 12.21]), and statins (MD = 6.72, [3.58; 9.85]). Spironolactone was also associated with a significant reduction in troponin elevation (MD = - 0.01, [- 0.02; - 0.01]). Enalapril demonstrated the greatest BNP reduction (MD = - 49.00, [- 68.89; - 29.11]), which was followed by spironolactone (MD = - 16.00, [- 23.9; - 8.10]). Additionally, patients on enalapril had the lowest risk of developing clinical HF compared to the control population (RR = 0.05, [0.00; 0.75]). CONCLUSION: Our analysis reaffirmed that statins, MRAs, ACEIs, and beta-blockers can significantly attenuate chemotherapy-induced cardiotoxicity, while ARBs showed no significant effects. Spironolactone showed the most robust improvement of LVEF, which best supports its use among this population. Our analysis warrants future clinical studies examining the cardioprotective effects of cardiac remodeling therapy in cancer patients treated with chemotherapeutic agents.

Nivolumab-Induced Myasthenia Gravis Concomitant With Myocarditis, Myositis, and Hepatitis.

We report a case of myasthenia gravis, myocarditis, and myositis following the treatment of melanoma with nivolumab. The patient was a 68-year-old Caucasian male with stage 3 melanoma status after two doses of nivolumab with shortness of breath, intermittent palpitations, dizziness, and nausea. During his initial evaluation, he was found to have atrial fibrillation with rapid ventricular response along with new-onset proximal muscle weakness, double vision, dysphagia, and ptosis of the right eye. Further diagnostic workup of the pleural effusion with CT of the chest showed large right pleural effusion with adjacent atelectasis. Thoracentesis was completed without complications and resulted in an exudative effusion with negative cytology and cultures. Serologic studies showed elevated troponin and serum creatine kinase, negative acetylcholine receptor antibody, and negative modulating antibody. Despite negative antibody tests, the patient's symptoms suggested a clinical diagnosis of myasthenia gravis. The ice pack test was performed, which showed temporary improvement of the patient's ptosis. Given the suspicion for myasthenia gravis and positive ice pack test, he was treated with corticosteroids, intravenous immunoglobulin (IVIG), and pyridostigmine. He completed a total of three doses of IVIG with improvement in diplopia. Despite steroids and respiratory support with BiPAP (bilevel positive airway pressure), on the 14th day of hospitalization, the patient had multiple organ failure along with worsening respiratory failure. The patient discussed the situation with his family, and they decided on hospice care. The patient was discharged to hospice on admission day 14.