Search

Aim: To define ruxolitinib failure and develop parameters to guide transition to next-line therapy for patients with myelofibrosis. Methods: A modified Delphi panel with 14 hematologists-oncologists. Survey concepts included defining primary refractory status, loss of response, disease progression, intolerance and transition to next-line therapy. Results: Ruxolitinib failure may be defined as no improvement in symptoms or spleen size, progressive disease or ruxolitinib intolerance, following a maximally tolerated dose for ≥3 months. Loss of spleen response 1 month after initial response may prompt discontinuation. Lack of evidence to inform transition to next-line therapy was noted; tapering ruxolitinib should be considered according to ruxolitinib dose and patient characteristics. Conclusion: Expert consensus was provided on defining ruxolitinib failure and transition to next-line therapy as summarized in this position paper, which may support considerations in the development of future clinical practice guidelines.

BACKGROUND We report a patient who was diagnosed with toxic myopericarditis secondary to hydrocarbon abuse using cardiac magnetic resonance imaging (CMR). CASE SUMMARY A 25-year-old male presented to emergency department with chest pain for 3 d. Patient also reported sniffing hydrocarbon containing inhalant for the last 1 year. Labs showed elevated troponin and electrocardiography was suggestive of acute pericarditis. Echocardiogram showed left ventricular (LV) ejection fraction (EF) of 40%. Given patient’s troponin elevation and reduced EF, cardiac catheterization was performed which showed normal coronaries. CMR was performed for myocardial infarction with non-obstructive coronary arteries evaluation. CMR showed borderline LV function with edema in mid and apical LV suggestive of myocarditis. CONCLUSION CMR can be used to diagnose toxic myopericarditis secondary to hydrocarbon abuse.

Ruxolitinib (RUX) is a first-line treatment for intermediate or high-risk myelofibrosis (MF) and was shown to improve splenomegaly and MF symptoms; however, patients experience loss of response and discontinuation rates are high (40%-70%). New treatment options have emerged for patients who are intolerant to or progress on RUX. The aim of the study was to establish how treatment failure can be defined in real-world practice and develop parameters to guide appropriate transition to next-line therapy.A 3-round modified Delphi panel was conducted with 14 hematologist-oncologists who had been a principal investigator on ≥1 clinical trial or involved in NCCN Guidelines for Myeloproliferative Neoplasms around the USA. Two survey rounds were completed via online questionnaires and scored using 9-point Likert scales, followed by a consensus meeting to resolve conflicting statements. Agreement was defined as ≥80% of respondents scoring 7-9 and disagreement 1-3.Eighty-four statements were agreed upon to define RUX failure. Consensus was reached for primary refractory treatment failure, defined as patients with no spleen/symptom response within ≥3 months while receiving a maximally tolerated dose. Loss of spleen/symptom response within ≥1 month following initial response or progressive disease, including to blast phase, were agreed upon as indicative of RUX failure. Intolerance can indicate RUX failure, presenting as treatment-emergent toxicities deemed unacceptable to the patient after ≥4 weeks of treatment. Additional consensus statements suggest that patient-reported symptoms of fatigue, poor concentration, inactivity, and bone pain were too general to define RUX failure versus other specific MF symptoms, i.e., night sweats. Following RUX failure, consensus recommendations suggest that next-line treatment should be guided by patient characteristics to mitigate risk of withdrawal and should start as soon as clinically appropriate.This research provides expert consensus on recognizing RUX failure in those with no treatment response or progression based on spleen and symptom control and intolerance. These definitions can be utilized to add guidance to future clinical guidelines or help providers recognize RUX failure in real-world practice. The study was supported by Bristol Myers Squibb. This work was previously presented at the 27th National Comprehensive Cancer Network (NCCN) Annual Conference, 2022.

294 Background: TRANSCEND NHL 001 (TRANSCEND; NCT02631044) evaluated efficacy and safety of the CAR T cell therapy lisocabtagene maraleucel (liso-cel) as third-line or later treatment in patients with R/R LBCL. Prior research demonstrated improvements in HRQOL with liso-cel; however, evidence of HRQOL in the context of CAR T cell‒specific adverse events was not evaluated. In TRANSCEND, the incidence of all-grade cytokine release syndrome (CRS) and neurological events (NE) was 42% and 30%, respectively. This analysis examined longitudinal HRQOL in the presence of CRS and NEs among clinical responders. Methods: Patients in TRANSCEND who responded to liso-cel treatment (n = 137) were stratified into 3 groups: no CRS or NEs, either CRS or NEs but not both, and both CRS and NEs. HRQOL was evaluated with the European Organisation for Research and Treatment of Cancer core quality of life questionnaire (QLQ-C30) and EQ-5D-5L. Summary statistics and change from baseline (liso-cel infusion; CFBL) were calculated for each time point. Results: For liso-cel‒treated patients who responded to treatment and developed CRS, NEs, or both, clinically relevant QLQ-C30 functional (physical, role, and cognitive) and fatigue scores indicated a noticeable nadir (low point) around 1 month post-baseline after liso-cel infusion, followed by a trend toward restoration of baseline status, generally achieved by 2 months after baseline. The primary difference between CRS/NE subgroups appeared to be the extent of decline or depth of the nadir. Patients with no CRS or NEs after liso-cel infusion did not experience an initial decrease in HRQOL/increase in symptom severity and instead showed a trend toward improvement over time (Table; QLQ-C30 fatigue as an illustrative example). This was also observed for EQ-5D-5L index scores. Conclusions: These findings support the anecdotal clinical experience that CRS/NEs are not associated with any long-term detriment in overall HRQOL and indicate a need for discussion with patients before treatment and early symptom monitoring and management of CRS or NEs. Clinical trial information: NCT02631044. [Table: see text]

Background Limb ischemia resulting from peripheral vascular disease is a common cause of morbidity. Vessel occlusion limits blood flow, creating a hypoxic environment that damages distal tissue, requiring therapeutic revascularization. Hypoxia‐inducible factors ( HIF s) are key transcriptional regulators of hypoxic vascular responses, including angiogenesis and arteriogenesis. Despite vascular smooth muscle cells’ ( VSMC s’) importance in vessel integrity, little is known about their functional responses to hypoxia in peripheral vascular disease. This study investigated the role of VSMC HIF in mediating peripheral ischemic responses. Methods and Results We used Arnt SMKO mice with smooth muscle–specific deletion of aryl hydrocarbon receptor nuclear translocator (ARNT, HIF ‐1β), required for HIF transcriptional activity, in a femoral artery ligation model of peripheral vascular disease. Arnt SMKO mice exhibit impaired perfusion recovery despite normal collateral vessel dilation and angiogenic capillary responses. Decreased blood flow manifests in extensive tissue damage and hypoxia in ligated limbs of Arnt SMKO mice. Furthermore, loss of aryl hydrocarbon receptor nuclear translocator changes the proliferation, migration, and transcriptional profile of cultured VSMC s. Arnt SMKO mice display disrupted VSMC morphologic features and wrapping around arterioles and increased vascular permeability linked to decreased local blood flow. Conclusions Our data demonstrate that traditional vascular remodeling responses are insufficient to provide robust peripheral tissue reperfusion in Arnt SMKO mice. In all, this study highlights HIF responses to hypoxia in arteriole VSMC s critical for the phenotypic and functional stability of vessels that aid in the recovery of blood flow in ischemic peripheral tissues.

To describe a minimally invasive surgical technique for procedures involving the caudoventral compartment of the thoracic cavity.Case series.Dogs (n = 13).Thirteen dogs; undergoing epicardial pacemaker implantation (9), palliative pericardial window (2), perforated right ventricle repair with epicardial pacemaker implantation (1), and peritoneopericardial diaphragmatic hernia (1) were operated by a transxiphoid approach. Dogs were positioned in dorsal recumbency and the bony xiphoid process was dissected free of adjoining tissue and transected proximally and distally. The distal transection was proximal to the cartilaginous junction of the process and the diaphragm. Entry to the thoracic cavity without penetration of the abdomen provided access for surgical treatment.All dogs recovered without complication. No dogs required thoracostomy tube placement.Transxiphoid approach is minimally invasive and provides adequate exposure for disorders of the caudoventral thoracic cavity.

Atrial fibrillation (AF) is the most commonly diagnosed supraventricular tachyarrhythmia in dogs. It typically develops when atrial enlargement occurs secondary to underlying cardiovascular disease. Electrocardiographically, AF is characterized by disorganized atrial electrical activity resulting in an absence of P waves and a rapid, irregular ventricular rate. The hemodynamic consequences of AF include decreased cardiac output and the development of clinical signs of heart failure. Therapeutic management focuses on controlling ventricular rate or restoring and maintaining sinus rhythm using antiarrhythmic medication and, in some cases, biphasic transthoracic electrical cardioversion. The prognosis varies and is especially guarded in the presence of significant underlying cardiac disease, such as dilated cardiomyopathy.