Clinical management of a patient following a granulocyte transfusion from a donor positive for COVID-19.

Granulocyte transfusions are indicated for patients with severe neutropenia and evidence of bacterial or fungal infection who are unresponsive to standard antimicrobial therapy. With a limited expiration time of 24 hours after collection, granulocytes are often transfused before results of infectious-disease screening tests are available, and before a transfusion service can perform a risk assessment if postdonation information is provided after the collection. The case we describe herein demonstrates a clinical scenario meeting indications for granulocyte transfusion, coupled with the clinical management undertaken after the granulocyte donor disclosed a positive result for a COVID-19 self-test taken 1 day after donation. In this case, the patient did not develop new COVID-19 symptoms and tested negative for COVID-19 after transfusion of the implicated unit. These findings add to the body of evidence in the literature that COVID-19 is not transmitted via blood transfusion.

Differences in Achilles tendon mechanical properties between professional ballet dancers and collegiate athletes utilizing shear wave elastography.

PURPOSE: To report normative stiffness parameters obtained using shear wave elastography in dorsiflexion from the Achilles tendons in asymptomatic professional ballet dancers and compare them with college-level athletes. METHODS: An Institutional Review Board (IRB)-approved study consists of 28 professional ballet dancers and 64 asymptomatic collegiate athletes. The athletes were further subdivided into runner and non-runner disciplines. Shear wave elastography (SWE) measurements were made in maximum ankle dorsiflexion position. RESULTS AND DISCUSSION: Forty-eight (52%) males and 44 (48%) females were examined with an overall mean age of 22.2 (± 3.8 years). There were no significant SWE differences between dominant and non-dominant legs in both groups and comparing spin vs. non-spin leg of ballet dancers (p > 0.05). Ballet dancers had significantly higher short-axis velocity values than runners and non-runners (2.34 m/s increase and 2.79 m/s increase, respectively, p < 0.001). Long-axis velocity was significantly higher in ballet dancers compared to non-runners (by 0.80 m/s, p < 0.001), but was not different between ballet dancers and runners (p > 0.05). Short-axis modulus was significantly higher in dancers compared to runners and non-runners (by 135.2 kPa and 159.2 kPa, respectively, p < 0.001). Long-axis modulus (LAM) was not significantly different in ballet dancers when compared to runners. CONCLUSION: Asymptomatic professional ballet dancers exhibit greater short-axis tendon stiffness compared to athletes and greater long-axis tendon stiffness compared to non-runners but similar to runners. The functional benefit from elevated short-axis stiffness in dancers is not clear but may be related to greater axial loading and adaptations of the tendon matrix.

Outcomes of a Remote Cardiac Rehabilitation Program for Patients Undergoing Atrial Fibrillation Ablation: Pilot Study.

BACKGROUND: Risk factor modification, in particular exercise and weight loss, has been shown to improve outcomes for patients with atrial fibrillation (AF). However, access to structured supporting programs is limited. Barriers include the distance from appropriate facilities, insurance coverage, work or home responsibilities, and transportation. Digital health technology offers an opportunity to address this gap and offer scalable interventions for risk factor modification. OBJECTIVE: This study aims to assess the feasibility and effectiveness of a 12-week asynchronous remotely supervised exercise and patient education program, modeled on cardiac rehabilitation programs, in patients with AF. METHODS: A total of 12 patients undergoing catheter ablation of AF were enrolled in this pilot study. Participants met with an exercise physiologist for a supervised exercise session to generate a personalized exercise plan to be implemented over the subsequent 12-week program. Disease-specific education was also provided as well as instruction in areas such as blood pressure and weight measurement. A digital health toolkit for self-tracking was provided to facilitate monitoring of exercise time, blood pressure, weight, and cardiac rhythm. The exercise physiologist remotely monitored participants and completed weekly check-ins to titrate exercise targets and provide further education. The primary end point was program completion. Secondary end points included change in self-tracking adherence, weight, 6-minute walk test (6MWT), waist circumference, AF symptom score, and program satisfaction. RESULTS: The median participant age was 67.5 years, with a mean BMI of 33.8 kg/m2 and CHADs2VASC (Congestive Heart Failure, Hypertension, Age [≥75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female]) of 1.5. A total of 11/12 (92%) participants completed the program, with 94% of expected check-ins completed and 2.9 exercise sessions per week. Adherence to electrocardiogram and blood pressure tracking was fair at 81% and 47%, respectively. Significant reductions in weight, waist circumference, and BMI were observed with improvements in 6MWT and AF symptom scores (P<.05) at the completion of the program. For program management, a mean of 2 hours per week or 0.5 hours per patient per week was required, inclusive of time for follow-up and intake visits. Participants rated the program highly (>8 on a 10-point Likert scale) in terms of the impact on health and wellness, educational value, and sustainability of the personal exercise program. CONCLUSIONS: An asynchronous remotely supervised exercise program augmented with AF-specific educational components for patients with AF was feasible and well received in this pilot study. While improvements in patient metrics like BMI and 6MWT are encouraging, they should be viewed as hypothesis generating. Based on insights gained, future program iterations will include particular attention to improved technology for data aggregation, adjustment of self-monitoring targets based on observed adherence, and protocol-driven exercise titration. The study design will need to incorporate strategies to facilitate the recruitment of a diverse and representative participant cohort.

Test then erase? Current status and future opportunities for Measurable Residual Disease testing in Acute Myeloid Leukemia.

BACKGROUND: Measurable residual disease (MRD) test positivity during and after treatment in patients with acute myeloid leukemia (AML) has been associated with higher rates of relapse and worse overall survival. Current approaches for MRD testing are not standardized leading to inconsistent results and poor prognostication of disease. Pertinent studies evaluating AML MRD testing at specific times points, with various therapeutics and testing methods are presented. SUMMARY: AML is a set of diseases with different molecular and cytogenetic characteristics, and is often polyclonal with evolution over time. This genetic diversity poses a great challenge for a single AML MRD testing approach. The current ELN 2021 MRD guidelines recommend MRD testing by quantitative polymerase chain reaction (qPCR) in those with a validated molecular target or multiparameter flow cytometry (MFC) in all other cases. The benefit of MFC is the ability to use this method across disease subsets, at the relative expense of suboptimal sensitivity and specificity. AML MRD detection may be improved with molecular methods. Genetic characterization at AML diagnosis and relapse is now standard of care for appropriate therapeutic assignment, future initiatives will provide the evidence to support testing in remission to direct clinical interventions. KEY MESSAGES: The treatment options for patients with AML have expanded for specific molecular subsets such as FLT3 and IDH1/2 mutated AML, with development of novel agents for NPM1 mutated or KMT2A rearranged AML ongoing, but also due to effective venetoclax-combinations. Evidence regarding highly sensitive molecular MRD detection methods for specific molecular subgroups, in the context of these new treatment approaches, will likely shape the future of AML care.

Prevalence of Urinary Incontinence and Other Pelvic Floor-Related Symptoms in Female Professional Dancers.

INTRODUCTION: Urinary incontinence (UI) is a common issue in female athletes and is known to negatively impact quality of life and sport performance. However, the prevalence of UI in dancers has not been widely investigated. The purpose of this study was to assess the prevalence of UI as well as other symptoms of pelvic floor dysfunction in female professional dancers. METHODS: An anonymous online survey that included the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) was developed and distributed via e-mail and social media. Two hundred and eight female professional dancers between the ages of 18 and 41 years (mean: 25.4 ± 5.2 years) who had a typical dance training and performance schedule of 25 hours or more per week completed the survey. RESULTS: A total of 34.6% of participants reported experiencing UI, with 31.9% of the dancers who reported UI reporting symptoms consistent with urge UI, 52.8% reporting UI with coughing or sneezing, and 54.2% reporting UI with physical activity or exercise. For those reporting UI, the mean ICIQ-UI SF score was 5.4 ± 2.5 points and the mean score for impact on everyday life was 2.9 ± 1.9. A report of pain with sexual activity and intercourse was significantly associated with presence of UI (p = 0.024), but the effect size was not notable (phi = 0.159). CONCLUSION: The prevalence of UI in female professional dancers is similar to that found in other high-level female athletes. Based on the notable prevalence of UI, health care professionals working with professional dancers should consider regularly screening for UI and other symptoms of pelvic floor dysfunction.

Tocilizumab for Cytokine Release Syndrome Management After Haploidentical Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis.

Cytokine release syndrome (CRS) is a common complication after haploidentical hematopoietic cell transplantation (HaploHCT). Severe CRS after haploHCT leads to higher risk of non-relapse mortality (NRM) and worse overall survival (OS). Tocilizumab (TOCI) is an interleukin-6 receptor inhibitor and is commonly used as first-line for CRS management after chimeric antigen receptor T cell therapy, but the impact of TOCI administration for CRS management on Haplo HCT outcomes is not known. In this single center retrospective analysis, we compared HCT outcomes in patients treated with or without TOCI for CRS management after HaploHCT with post-transplantation cyclophosphamide- (PTCy-) based graft-versus-host disease (GvHD) prophylaxis. Of the 115 patients eligible patients who underwent HaploHCT at City of Hope between 2019 to 2021 and developed CRS, we identified 11 patients who received tocilizumab for CRS management (TOCI). These patients were matched with 21 patients who developed CRS but did not receive tocilizumab (NO-TOCI) based on age at the time of HCT (≤64 years or >65 years or older), conditioning intensity (myeloablative versus reduced-intensity/nonmyeloablative), and CRS grading (1, 2, versus 3-4). Instead of 22 controls, we chose 21 patients because there was only 1 control matched with 1 TOCI treatment patient in 1 stratum. With only 11 patients in receiving tocilizumab for CRS treatment, matching with 21 patients who developed CRS but did not receive tocilizumab, we had 80% power to detect big differences (hazard ratio [HR] = 3.4 or higher) in transplantation outcomes using a 2-sided 0.05 test. The power would be reduced to about 20% to 30% if the difference was moderate (HR = 2.0) using the same test. No CRS-related deaths were recorded in either group. Median time to neutrophil engraftment was 21 days (range 16-43) in TOCI and 18 days (range 14-23) in NO-TOCI group (HR = 0.55; 95% confidence interval [CI] = 0.28-1.06, P = .08). Median time to platelet engraftment was 34 days (range 20-81) in TOCI and 28 days (range 12-94) in NO-TOCI group (HR = 0.56; 95% CI = 0.25-1.22, P = .19). Cumulative incidences of day 100 acute GvHD grades II-IV (P = .97) and grades III-IV (P = .47) were similar between the 2 groups. However, cumulative incidence of chronic GvHD at 1 year was significantly higher in patients receiving TOCI (64% versus 24%; P = .05). Rates of NRM (P = .66), relapse (P = .83), disease-free survival (P = .86), and overall survival (P = .73) were similar at 1 year after HCT between the 2 groups. Tocilizumab administration for CRS management after HaploHCT appears to be safe with no short-term adverse effect and no effect on relapse rate. However, the significantly higher cumulative incidence of chronic GvHD, negates the high efficacy of PTCy on GvHD prophylaxis in this patient population. Therefore using tocilizumab for CRS management in the HaploHCT population with PTCy maybe kept only for patients with severe CRS. The impact on such approach on long term outcome in HaploHCT with PTCy will need to be evaluated in a larger retrospective study or a prospective manner.

Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) have been increasingly used as first-line therapy in hematologic and solid-organ malignancies. Multiple TKIs have been linked with the development of cardiovascular complications, especially atrial arrhythmias, but data on ventricular arrhythmias (VAs) is scarce. METHODS: Herein we describe five detailed cases of VAs related to TKI use in patients with varied baseline cardiovascular risk factors between 2019 and 2022 at three centers. Individual chart review was conducted retrospectively. RESULTS: Patient ages ranged from 43 to 83 years. Three patients were on Bruton's TKI (2 ibrutinib and 1 zanubrutinib) at the time of VAs; other TKIs involved were afatinib and dasatinib. Three patients had a high burden of non-sustained ventricular tachycardia (NSVT) requiring interventions, whereas two patients had sustained VAs. While all patients in our case series had significant improvement in VA burden after TKI cessation, two patients required new long-term antiarrhythmic drug therapy, and one had an implantable defibrillator cardioverter (ICD) placed due to persistent VAs after cessation of TKI therapy. One patient reinitiated TKI therapy after control of arrhythmia was achieved with antiarrhythmic drug therapy. CONCLUSIONS: Given the expanding long-term use of TKIs among a growing population of cancer patients, it is critical to acknowledge the association of TKIs with cardiovascular complications such as VAs, to characterize those at risk, and deploy preventive and therapeutic measures to avoid such complications and interference with oncologic therapy. Further efforts are warranted to develop monitoring protocols and optimal treatment strategies for TKI-induced VAs.

FLT3 Inhibitors as Maintenance Therapy after Allogeneic Stem-Cell Transplantation.

Mutations in the FLT3 gene are associated with poor prognosis in patients with AML, even after consolidation with allogeneic hematopoietic cell transplantation (alloHCT) in first remission. Treatment failure in FLT3-mutated AML is largely driven by excessive risk of relapse compared to other genetic subtypes, including in patients post-alloHCT. As a result, there is substantial interest in studying posttransplant maintenance therapy in FLT3-mutated AML as an approach to optimize disease control and improve long-term outcomes. Clinical trials utilizing posttransplant FLT3 inhibitors, such as sorafenib and midostaurin, have shown feasibility, safety, and encouraging posttransplant outcomes, and there are ongoing studies using newer-generation tyrosine-kinase inhibitors as posttransplant maintenance therapy. Here, we review the toxicities and efficacy of FLT3 inhibitors as posttransplant maintenance, recommendations on the use of FLT3 inhibitors by international consensus guidelines, and highlight key remaining questions.

Dry Needling and Acupuncture in Treatment of Dance-Related Injuries, MD, and PT Perspectives.

Dancers frequently present to health care professionals with musculoskeletal impairments. The role of the health care practitioner, whether physician, physical therapist, or acupuncturist, is to decrease pain and restore function in the short term and to restore adaptive potential and neural connectivity in the long term. When dysfunction is treated, pain improves. Acupuncture and dry needling improve tissue perfusion by improving vasomotor control and can improve strength by removing motor inhibition. Acupuncture and dry needling are safe, complementary modalities aimed at improving the function of the dancer.

Spotlight on Mogamulizumab-Kpkc for Use in Adults with Relapsed or Refractory Mycosis Fungoides or Sézary Syndrome: Efficacy, Safety, and Patient Selection.

Advanced cutaneous T cell lymphomas (CTCL) including mycosis fungoides (MF) and Sézary syndrome (SS) are often difficult to manage once they become resistant to initial systemic treatment. Current systemic treatments usually provide a limited duration of disease control, leaving this an area in desperate need of new treatment options for better long-term control. These conditions often affect the older population where transplantation may not be a feasible option. Recent studies evaluated a novel CCR4 humanized monoclonal antibody, mogamulizumab, in relapsed/refractory MF and SS, which show a meaningful progression free survival (PFS) benefit. In August 2018, mogamulizumab was approved by the FDA for the treatment of patients with relapsed/refractory MF/SS who have failed at least one treatment. Approval was based on the Phase III MAVORIC study comparing mogamulizumab to vorinostat, an FDA approved drug for this indication, in 372 patients. In this trial, mogamulizumab was found to have a superior PFS with a median of 7.7 months compared to 3.1 months in the vorinostat arm, with a hazard ratio of 0.53, p<0.001. Mogamulizumab was well tolerated with the most common AE being infusion-related reactions (32%), drug rash (20%), diarrhea (23%), and fatigue (22%). We reviewed the literature leading to the development and approval of mogamulizumab and suggest which patients may benefit the most from this treatment.

Key Role of Inflammation in Myeloproliferative Neoplasms: Instigator of Disease Initiation, Progression. and Symptoms.

PURPOSE OF REVIEW: Chronic inflammation is a characteristic feature of myeloproliferative neoplasm (MPN) and impacts many aspects of the disease including initiation, progression, and symptomatology. RECENT FINDINGS: The chronic inflammatory state of MPN results from disruption of immune signaling pathways leading to overproduction of inflammatory cytokines by both the neoplastic clones and bystander immune cells. This chronic inflammation may allow for the neoplastic clone to gain a selective advantage. The symptomatic burden felt by MPN patients may be a result of the chronic inflammation associated with MPN, as several cytokines have been linked with different symptoms. Pharmacologic as well as nonpharmacologic treatments of the inflammatory component of this disease may lead to decreased symptomatic burden, prevention of disease progression, and improvement in overall disease trajectory. Inflammation plays a key role in the pathogenesis of MPN and represents an important therapeutic target.

Fluconazole Resistance Patterns in Candida Species that Colonize Women with HIV Infection.

BACKGROUND: The Women's Interagency HIV Study was established in 1993 to study the natural history of HIV disease among women in the United States. It currently has enrolled 2,895 women testing positive for HIV infection and 972 women without HIV infection recruited from 6 national metropolitan locations. The clinical database information collected for each HIV-positive individual included CD4 cell counts, viral load, and antiviral treatment to evaluate HIV prognosis and related conditions in women. OBJECTIVE: To provide a baseline for fluconazole treatment prospects in women who test positive for HIV infection. As part of the ongoing Women's Interagency HIV Study project, we investigated the fluconazole susceptibility of Candida spp. isolated from women with HIV in comparison to volunteer women without HIV. The implication of antifungal treatment on fluconazole susceptibility was evaluated by reviewing antifungal medication use for the past 2 years in each participant. In addition, genotyping of Candida spp. at oral and vaginal sites was monitored for 4 months in 9 patients. METHODS: In a cohort of 59 women with HIV and 24 women without HIV, colonization by Candida albicans and non-albicans species of the oral and vaginal sites was first determined. Fluconazole susceptibility was surveyed in vitro according to Clinical and Laboratory Standards Institute protocol. Antifungal drug treatment history was investigated for each patient to correspond with fluconazole susceptibility. Finally, series of isolates from several patients were followed for resistance and susceptibility. Their lineage was verified by genotyping multilocus sequence typing (MLST). RESULTS: A total of 280 Candida strains were recovered from oral and vaginal swabs of women with and without HIV infection. We found that patients with HIV were colonized with Candida spp. more frequently than women without HIV. The percent of isolates that were susceptibility dose dependent or resistant to fluconazole was higher in Candida glabrata compared with C. albicans isolates, but higher for C. albicans than other published data. Resistance was noted to be more common in vaginal sites. Fluconazole resistance in either species was not associated with relative CD4 cell counts or viral load. However an association with systemic application of fluconazole and resistance was noted. CONCLUSIONS: Systemic antifungal therapy, including a vaginal topical regimen in women with HIV infection correlated with reduced fluconazole susceptibility of oral and vaginal isolates. Genotype profiling has disclosed that a majority of isolates from the same individual are clustered together, suggesting the likelihood of an original strain with some microevolution. We observed a change from a susceptibility dose dependent to a resistant phenotype of isolates in 2 women with HIV infection, even though no treatments were received during the 4-month study and the prior 2 years.