Oral Decitabine/Cedazuridine Is an Effective Ambulatory Therapy for Patients With Myelofibrosis Refractory to JAK2 Inhibitor Therapy.

BACKGROUND: Outcomes are dismal for patients with myelofibrosis (MF) who are no longer responsive to JAK2 inhibitors (JAKi) and/or have increasing blast cell numbers. Although prior reports have suggested the benefits of intravenous decitabine (DAC) combined with ruxolitinib for patients with Myeloproliferative Neoplasm (MPN) accelerated/blast phase (AP/BP), decitabine-cedazuridine (DEC-C), an oral fixed-dose combination providing equivalent pharmacokinetic exposure, has not been evaluated in MF. METHODS: We conducted a retrospective analysis of 14 patients with high-risk MF refractory to ruxolitinib or MPN-AP (10-19% blasts) treated with DEC-C +/- JAKi at Mount Sinai Hospital from 2021 to 2024. RESULTS: The cohort was elderly (median age,76 years) and almost uniformly possessed high risk mutations with 13 of the 14 patients progressing on JAKi therapy. With a median follow-up of 9.4 months, the median overall survival (OS) was 29 months for the entire cohort. Median OS was 10.8 months for MPN-AP and was not reached for ruxolitinib refractory MF patients. All patients (n = 9) receiving > 4 cycles of DEC-C had clinical benefit exemplified by a reduction in blast cell numbers, spleen size, and lack of progression to MPN-BP (78%). Furthermore, 3/14 patients proceeded to allogeneic stem cell transplant. Myelosuppression was a common adverse event which was managed by reducing the number of days of administration of DEC-C from 5 to 3 per cycle. CONCLUSIONS: This report demonstrates the feasibility, tolerability, and clinical benefit of an exclusively ambulatory regimen for high-risk, elderly patients with advanced MF which warrants further evaluation in a prospective clinical trial.

Interstitial lung disease diagnosis and prognosis using an AI system integrating longitudinal data.

For accurate diagnosis of interstitial lung disease (ILD), a consensus of radiologic, pathological, and clinical findings is vital. Management of ILD also requires thorough follow-up with computed tomography (CT) studies and lung function tests to assess disease progression, severity, and response to treatment. However, accurate classification of ILD subtypes can be challenging, especially for those not accustomed to reading chest CTs regularly. Dynamic models to predict patient survival rates based on longitudinal data are challenging to create due to disease complexity, variation, and irregular visit intervals. Here, we utilize RadImageNet pretrained models to diagnose five types of ILD with multimodal data and a transformer model to determine a patient's 3-year survival rate. When clinical history and associated CT scans are available, the proposed deep learning system can help clinicians diagnose and classify ILD patients and, importantly, dynamically predict disease progression and prognosis.

Influence of thoracic radiology training on classification of interstitial lung diseases.

INTRODUCTION: Interpretation of high-resolution CT images plays an important role in the diagnosis and management of interstitial lung diseases. However, interreader variation may exist due to varying levels of training and expertise. This study aims to evaluate interreader variation and the role of thoracic radiology training in classifying interstitial lung disease (ILD). METHODS: This is a retrospective study where seven physicians (radiologists, thoracic radiologists, and a pulmonologist) classified the subtypes of ILD of 128 patients from a tertiary referral center, all selected from the Interstitial Lung Disease Registry which consists of patients from November 2014 to January 2021. Each patient was diagnosed with a subtype of interstitial lung disease by a consensus diagnosis from pathology, radiology, and pulmonology. Each reader was provided with only clinical history, only CT images, or both. Reader sensitivity and specificity and interreader agreements using Cohen's κ were calculated. RESULTS: Interreader agreement based only on clinical history, only on radiologic information, or combination of both was most consistent amongst readers with thoracic radiology training, ranging from fair (Cohen's κ: 0.2-0.46), moderate to almost perfect (Cohen's κ: 0.55-0.92), and moderate to almost perfect (Cohen's κ: 0.53-0.91) respectively. Radiologists with any thoracic training showed both increased sensitivity and specificity for NSIP as compared to other radiologists and the pulmonologist when using only clinical history, only CT information, or combination of both (p < 0.05). CONCLUSIONS: Readers with thoracic radiology training showed the least interreader variation and were more sensitive and specific at classifying certain subtypes of ILD. SUMMARY SENTENCE: Thoracic radiology training may improve sensitivity and specificity in classifying ILD based on HRCT images and clinical history.

Cardiac Dysfunction in Neonatal HIE Is Associated with Increased Mortality and Brain Injury by MRI.

OBJECTIVE: Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions. RESULTS: A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p = 0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p = 0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p = 0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction. CONCLUSION: Newborns who died or had moderate-to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities. KEY POINTS: · Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury.. · All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction.. · When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function..

Altered biventricular function in neonatal hypoxic-ischaemic encephalopathy: a case-control echocardiographic study.

BACKGROUND: In newborns with hypoxic-ischaemic encephalopathy, more profound altered right and left ventricular function has been associated with mortality or brain injury. Mechanisms underlying cardiac dysfunction in this population are thought to be related to the persistence of increased pulmonary vascular resistance and myocardial ischaemia. We sought to compare cardiac function in newborns with hypoxic-ischaemic encephalopathy to controls using echocardiography. METHODS: We did a retrospective case-control study with moderate or severe hypoxic-ischaemic encephalopathy between 2008 and 2017. Conventional and speckle-tracking echocardiography measures were extracted to quantify right and left ventricular systolic and diastolic function. Fifty-five newborns with hypoxic-ischaemic encephalopathy were compared to 28 controls. RESULTS: Hypoxic-ischaemic encephalopathy newborns had higher estimated systolic pulmonary pressure (62.5 ± 15.0 versus 43.8 ± 17.3 mmHg, p < 0.0001) and higher systolic pulmonary artery pressure/systolic blood pressure ratio [101 ± 16 (iso-systemic) versus 71 ± 27 (2/3 systemic range) %, p < 0.0001]. Tricuspid annular plane systolic excursion was decreased (7.5 ± 2.2 versus 9.0 ± 1.4 mm, p = 0.002), E/e' increased (7.9 ± 3.3 versus 5.8 ± 2.0, p = 0.01), and right ventricle-myocardial performance index increased (68.1 ± 21.5 versus 47.8 ± 9.5, p = 0.0001) in hypoxic-ischaemic encephalopathy. Conventional markers of left ventricle systolic function were similar, but e' velocity (0.059 ± 0.019 versus 0.070 ± 0.01, p = 0.03) and left ventricle-myocardial performance index were statistically different (77.9 ± 26.2 versus 57.9 ± 11.2, p = 0.001). The hypoxic-ischaemic encephalopathy group had significantly altered right and left ventricular deformation parameters by speckle-tracking echocardiography. Those with decreased right ventricle-peak longitudinal strain were more likely to have depressed left ventricle-peak longitudinal strain. CONCLUSION: Newborns with hypoxic-ischaemic encephalopathy have signs of increased pulmonary pressures and altered biventricular systolic and diastolic function.

Effect of Wendler Glottoplasty on Acoustic Measures of Voice.

OBJECTIVES: Voice therapy has been the primary treatment for voice feminization in transfemale patients due to concerns that surgery worsens voice quality. We aim to determine the impact of Wendler glottoplasty on acoustic measures of voice. STUDY DESIGN: Retrospective case series. METHODS: Transgender female patients treated for vocal feminization with Wendler glottoplasty at a single tertiary care center were identified. Pre- and postoperative measures were taken with the Kay Elemetrics Real-Time Pitch, Analysis of Dysphonia in Speech and Voice, and Multidimensional Voice Program. RESULTS: Twenty-eight patients were included in this study. There were no statistically significant changes in fundamental frequency variation, peak amplitude variation, soft phonation index, noise-to-harmonics ratio, cepstral peak prominence, or cepstral spectral index of dysphonia at a significance level of P < .05. Average speaking fundamental frequency (SF0) increased from 143 Hz after voice therapy to 163 Hz after surgery (P = .0009). Lower range decreased in 61% and increased in 26% of patients. Upper range decreased in 52% and increased in 48% of patients. CONCLUSIONS: Wendler glottoplasty does not worsen voice quality based on acoustic measures. Although most patients experience an increase in average SF0, effects on vocal range are variable with approximately half of patients experiencing a reduction and half experiencing an increase in upper pitch limit. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:583-586, 2021.

Addition of Wendler Glottoplasty to Voice Therapy Improves Trans Female Voice Outcomes.

OBJECTIVES/HYPOTHESIS: VT is often considered the preferred treatment for vocal feminization in transgender patients. However, Wendler glottoplasty offers a surgical option for increasing fundamental frequency and perception of vocal femininity. We aimed to determine whether the addition of glottoplasty to VT results in greater fundamental frequency elevation and improvement in quality-of-life measures. STUDY DESIGN: Retrospective case series. METHODS: Forty-eight trans female patients were treated for vocal feminization. Twenty-seven patients underwent VT, and 21 patients underwent VT with additional glottoplasty (VTWG). Pre- and posttreatment acoustic measures, Trans Woman Voice Questionnaire (TWVQ), and Voice Handicap Index-10 (VHI-10) data were compared. RESULTS: Glottoplasty in combination with VT elevated average speaking fundamental frequency (SF0) to a greater extent than VT alone (P < .0001). The VTWG group achieved a 42-Hz increase in SF0, whereas the VT group achieved a 15-Hz increase in SF0. In both the VT and VTWG groups, the lower bound of physiologic range increased by 18 Hz (P = .0008 and P = .016, respectively). The addition of glottoplasty also resulted in greater improvement in voice-related quality of life. Improvement in TWVQ and VHI-10 was significantly greater in the VTWG group than the VT group (P = .007 and P = .029, respectively). TWVQ showed statistically significant improvement in the VTWG group only. CONCLUSIONS: VT results in SF0 elevation and improvement in VHI-10. The addition of glottoplasty to VT results in further improvements in SF0 and VHI-10 and statistically significant improvement in TWVQ. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1588-1593, 2021.