Citations

Abstract Lineage switch (LS), defined as the immunophenotypic transformation of acute leukemia, has emerged as a mechanism of relapse after antigen-targeted immunotherapy, which is associated with dismal outcomes. Through an international collaborative effort, we identified cases of LS after a host of antigen-targeted therapies (eg, CD19, CD22, CD38, and CD7), described how LS was diagnosed, reviewed treatment approaches, and analyzed overall outcomes for this form of postimmunotherapy relapse. Collectively, 75 cases of LS were evaluated, including 53 (70.7%) cases of B-cell acute lymphoblastic leukemia (B-ALL) transforming to acute myeloid leukemia (AML), 17 (22.7%) cases of B-ALL transforming to mixed phenotypic acute leukemia (MPAL)/acute leukemias of ambiguous lineage (ALAL), and 5 (6.7%) cases of rare LS presentation (ie, T-cell ALL to AML). An additional 10 cases with incomplete changes in immunophenotype, referred to as “lineage drift” were also described. With a primary focus on the 70 cases of LS from B-ALL to AML or MPAL/ALAL, LS emerged at a median of 1.5 months (range, 0-36.5) after immunotherapy, with 81.4% presenting with LS within the first 6 months from the most proximal immunotherapy. Although most involved KMT2A rearrangements (n = 45, 64.3%), other rare cytogenetic and/or molecular alterations were uniquely observed. Treatment outcomes were generally poor, with remission rates of <40%. The median overall survival after LS diagnosis was 4.8 months. Outcomes were similarly poor for those with rare immunophenotypes of LS or lineage drift. This global initiative robustly categorizes lineage changes after immunotherapy and, through enhanced understanding, establishes a foundation for improving outcomes of LS.

Background: No biomechanical study has established the effect of different graft positions or bone block options on anterior glenohumeral joint stability. Purpose/Hypothesis: The purpose of this study was to compare graft choice (distal clavicular vs coracoid autograft for Latarjet) and position on stability of the bone block for anterior glenohumeral instability. It was hypothesized that both grafts would be comparable if flush with the glenoid but that the sling effect of the Latarjet procedure would lead to greater stability in case of graft medialization. Study Design: Controlled laboratory study. Methods: Eight cadaveric shoulders were included. Defects stabilized using a distal clavicular graft and a coracoid graft were consecutively positioned at 0, 4, and 8 mm medially. The starting position was determined by the humeral head’s being seated at its most medial position on the glenoid surface. Each experiment comprised maximal external rotation and glenohumeral abduction at 60° while applying a constant 50-N medial compressive force to the humerus under all conditions. The conjoint tendon was routed through a split in the subscapularis and loaded with a 5-N weight using a pulley system for all Latarjet trials to simulate the sling effect. Results: Regarding the clavicular graft, the stability ratio significantly decreased versus the intact condition at all medial offsets ( P = .007 for 0 mm, P < .001 for 4 mm, and P < .001 for 8 mm), and it was significantly lower in the 4-mm versus 0-mm position ( P = .008), significantly higher in the 4-mm versus 8-mm position ( P < .001), and significantly lower in the 8-mm versus 0-mm position ( P < .001). Regarding the coracoid graft, the stability ratio was comparable with intact for the 0-mm position ( P = .12), while it was significantly lower in the 4-mm and 8-mm positions ( P < .001 for both). The distal clavicular graft at 0-mm offset was comparable with the coracoid graft at 0-mm offset. Conclusion: In shoulders with anterior glenoid bone loss, the coracoid and distal clavicular autografts were biomechanically comparable when placed flush with the glenoid. The distal clavicle at 0-mm offset did not restore stability compared with the intact specimen, but the Latarjet at 0-mm offset was not significantly different from the intact condition. Clinical Relevance: The Latarjet procedure provides higher stability compared with distal clavicular autograft when medialized.

BACKGROUND: Bioprosthetic valve dysfunction and reoperations/reinterventions are common after aortic valve replacement (AVR) with bioprosthetic valves, leading to cycles of left ventricular (LV) pressure overload and unloading. The purpose of this study was to compare postoperative changes in LV structure and function and their relationship to clinical outcomes in young patients who underwent AVR with bioprosthetic valves (Bio_AVR group) versus mechanical prosthetic valves (Mech_AVR group). METHODS: Retrospective study of adults with congenital heart disease who underwent AVR at Mayo Clinic (2003–2023). The Bio_AVR group was matched 1:2 to the Mech_AVR group. LV indices (LV mass index, relative wall thickness, LV global longitudinal strain, averaged e′, and averaged E/e′) and clinical indices (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and New York Heart Association class) were assessed preoperatively, and at 1, 5, and 10 years post-AVR. RESULTS: We studied 151 and 302 patients in the Bio_AVR and Mech_AVR groups, respectively (age 38±16 years, 58% males). Both groups had similar LV and clinical indices at baseline and 1 year post-AVR. However, the Bio_AVR group had higher LV mass index, relative wall thickness, and averaged E/e′, and lower averaged e′ and LV global longitudinal strain at 5 and 10 years post-AVR. Of 51 patients from the Bio_AVR group who underwent a second AVR, there was less robust improvement in LV indices and clinical indices after the second AVR compared with the first AVR. CONCLUSIONS: AVR with a bioprosthetic valve was associated with progressive LV hypertrophy and dysfunction, and worsening clinical status compared with mechanical prosthetic valves. This provides further evidence against the use of bioprosthetic AVR in young patients.

OBJECTIVE Triceps motor branch transfer to the anterior division of the axillary nerve (AXN) was originally described for patients with a loss of deltoid function secondary to upper trunk (UT) brachial plexus injuries but has evolved to restore deltoid function in isolated peripheral AXN injuries. The purpose of this study was to compare functional outcomes in patients who had undergone this procedure in the setting of UT brachial plexus injury versus peripheral AXN injury. METHODS The records of patients who had undergone triceps branch to anterior division of the AXN transfer at a single academic institution between 2001 and 2023 were retrospectively reviewed. Patients were included in the study if they had either a UT or an AXN injury and were excluded if their follow-up was less than 2 years. Pre- and postoperative outcomes, including modified British Medical Research Council grade and range of motion, were compared between the two groups. RESULTS Forty-two patients met the criteria for inclusion. Thirty cases were classified as UT injury and 12 cases as AXN injury. The mean postoperative abduction strength was significantly higher in the AXN injury group (3.2 ± 1.5 vs 1.9 ± 1.2, p = 0.007), as was the postoperative change in abduction strength (2.8 ± 1.7 vs 1.6 ± 1.4, p = 0.01). The mean postoperative forward flexion (136° ± 57° vs 79° ± 54°, p = 0.005) and abduction (129° ± 64° vs 59° ± 47°, p = 0.004) were significantly better in the AXN group, although postoperative changes in flexion and abduction were not different between the groups. Triceps strength preoperatively was similar to that postoperatively in both groups. CONCLUSIONS Patients with an AXN injury, compared to those with a UT injury, had better postoperative abduction strength and shoulder range of motion after triceps branch transfer to the anterior division of the AXN. Triceps strength was not significantly changed after the procedure in the two groups. The study findings suggest that the outcomes of triceps branch transfer to the anterior division of the AXN are different based on the location and type of injury, providing insight into prognosis while counseling patients.

Abstract Preeclampsia and other hypertensive disorders of pregnancy are major contributors to maternal morbidity and mortality worldwide. This group of disorders includes chronic hypertension, gestational hypertension, preeclampsia, preeclampsia superimposed on chronic hypertension, and eclampsia. The body undergoes important physiological changes during pregnancy to allow for normal placental and fetal development. Several mechanisms have been proposed that may lead to preeclampsia, including abnormal placentation and placental hypoxia, impaired angiogenesis, excessive pro‐inflammatory response, immune system imbalance, abnormalities of cellular senescence, alterations in regulation and activity of angiotensin II, and oxidative stress, ultimately resulting in upregulation of multiple mediators of endothelial cell dysfunction leading to maternal disease. The clinical implications of preeclampsia are significant as there are important short‐term and long‐term health consequences for those affected. Preeclampsia leads to increased risk of preterm delivery and increased morbidity and mortality of both the developing fetus and mother. Preeclampsia also commonly leads to acute kidney injury, and women who experience preeclampsia or another hypertensive disorder of pregnancy are at increased lifetime risk of chronic kidney disease and cardiovascular disease. An understanding of normal pregnancy physiology and the pathophysiology of preeclampsia is essential to develop novel treatment approaches and manage patients with preeclampsia and hypertensive disorders of pregnancy. © 2023 American Physiological Society. Compr Physiol 13:4231‐4267, 2023.

ABSTRACT Background The relationship between height differences related to graft anatomy and physiological pressure indices in coronary bypass grafts has not been studied. We sought to study the impact of hydrostatic pressure on fractional flow reserve (FFR) in saphenous vein grafts (SVGs). Methods Included were 66 symptomatic patients (76 SVGs) with prior coronary artery bypass grafting who underwent coronary computed tomography angiography (CCTA) preceding invasive coronary angiography with FFR interrogation of ≥ 1 SVGs. The graft course and height excursion were reconstructed based on CCTA images. The impact of hydrostatic pressure on FFR (corrected FFR) was calculated by adding or subtracting 0.077 mmHg to the distal coronary pressure for every millimeter height difference in a supine position between the SVG ostium and the pressure wire tip position. Results The height difference (mm) between the SVG ostium and pressure wire tip position was largest for single SVGs to the circumflex artery (Cx; −55.1 ± 17.0), followed by sequential SVGs to the Cx (−51.8 ± 17.3) and the right coronary artery (RCA; −36.7 ± 21.6). The correlation between height difference and uncorrected FFR was −0.59 ( p < 0.001). Corrected FFR was lower as compared to uncorrected FFR in the overall cohort (0.86 ± 0.17 vs. 0.88 ± 0.18), in single SVGs to Cx (0.85 ± 0.17 vs. 0.90 ± 0.18), and in sequential SVGs to Cx (0.92 ± 0.14 vs. 0.96 ± 0.15) and RCA (0.82 ± 0.17 vs. 0.85 ± 0.21) ( p < 0.001 for all). Conclusions Hydrostatic pressure related to height differences along the course anatomy of SVGs can impact FFR measurements, with corrected FFR being significantly lower in SVGs to the Cx and sequential SVGs to the RCA.