Citations

We describe the design and results from the BraTS 2023 Intracranial Meningioma Segmentation Challenge. The BraTS Meningioma Challenge differed from prior BraTS Glioma challenges in that it focused on meningiomas, which are typically benign extra-axial tumors with diverse radiologic and anatomical presentation and a propensity for multiplicity. Nine participating teams each developed deep-learning automated segmentation models using image data from the largest multi-institutional systematically expert annotated multilabel multi-sequence meningioma MRI dataset to date, which included 1000 training set cases, 141 validation set cases, and 283 hidden test set cases. Each case included T2, FLAIR, T1, and T1Gd brain MRI sequences with associated tumor compartment labels delineating enhancing tumor, non-enhancing tumor, and surrounding non-enhancing FLAIR hyperintensity. Participant automated segmentation models were evaluated and ranked based on a scoring system evaluating lesion-wise metrics including dice similarity coefficient (DSC) and 95% Hausdorff Distance. The top ranked team had a lesion-wise median dice similarity coefficient (DSC) of 0.976, 0.976, and 0.964 for enhancing tumor, tumor core, and whole tumor, respectively and a corresponding average DSC of 0.899, 0.904, and 0.871, respectively. These results serve as state-of-the-art benchmarks for future pre-operative meningioma automated segmentation algorithms. Additionally, we found that 1286 of 1424 cases (90.3%) had at least 1 compartment voxel abutting the edge of the skull-stripped image edge, which requires further investigation into optimal pre-processing face anonymization steps.

Abstract Purpose: Digital proteomic profiling was performed to identify spatial context in relationship to patient response and survival after anti–PD-1 therapy in metastatic colorectal cancer. Experimental Design: Primary colorectal cancers with deficient mismatch repair from patients treated with anti–PD-1 antibodies were analyzed (N = 30) using digital spatial profiling (GeoMx nCounter). At the invasive margin, 71 proteins were profiled in 10 regions of interest/slide that were segmented into 3 compartments labeled with pan-cytokeratin (epithelia), CD45 (stromal cells), and SYTO13 (nuclei). In an independent cohort (n = 13), digital spatial profiling data and single-cell transcriptomic data were analyzed. Differential protein abundance, after Benjamini–Hochberg correction, was examined by clinical response and progression-free survival (PFS) using multivariable Cox regression. Results: Protein abundance varied significantly between epithelial and stromal compartments. Nonresponders to anti–PD-1 showed higher fibronectin and smooth muscle actin abundance in the epithelial compartment that was associated with significantly shorter PFS (adjusted HR: 6.49 and 4.52, respectively; P < 0.05). In CD45+ stroma, increased expression of proteins related to T cells (CD3 and CD4), NK cells (CD56), antigen presentation (CD40), immune activation (CD27, ICOS), and apoptosis (GZMA) were found in responders (vs nonresponders) to anti–PD-1; each marker was significantly associated with longer patient PFS (0.02 < adjusted HR < 0.17; P < 0.05). In a separate cohort, consistent results by compartment were found for fibronectin and CD56. Gene expression data revealed that fibronectin and smooth muscle actin were primarily derived from cancer-associated fibroblasts. Conclusions: Spatially resolved protein profiles within microenvironments of deficient mismatch repair colorectal cancers can influence patient response and survival after anti–PD-1, highlighting their potential clinical significance.

ABSTRACT Background and Hypothesis Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B cell maturation antigen (BCMA), and chimeric antigen receptor T cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy. Methods This was a retrospective study involving 64 patients with relapsed/refractory MM treated with either teclistamab or CAR-T therapy. All patients had previously received at least four lines of chemotherapy before being treated with either teclistamab or CAR-T. The primary outcome was the incidence of AKI, and secondary outcomes included AKI severity, kidney recovery rates, and mortality. Kaplan–Meier estimates for AKI-free survival were calculated, and hazard ratios (HRs) for AKI risk were determined using Cox proportional hazards models. Results Sixty-four patients met inclusion criteria for this study (30 received CAR-T and 34 received teclistamab therapy). Among these patients, 14 AKI events occurred in total (22%), with 10 events (29%) in the teclistamab group and four events (13%) in the CAR-T group. AKI-free survival estimates at 180 days after treatment initiation were 68% [95% confidence interval (CI): 53%–87%] for teclistamab patients and 90% (95% CI: 79%–100%) for CAR-T patients. While patients receiving teclistamab were found to have an increased risk of an AKI event compared to those receiving CAR-T therapy, the results were not statistically significant [HR (95% CI): 3.38 (0.93–12.31), P = .065]. Conclusions This study suggests that patients treated with teclistamab may experience a higher incidence of AKI compared to those receiving CAR-T therapy. However, further research is required to determine whether this increased risk is attributable to disease progression or teclistamab itself. These results highlight the need for close kidney function monitoring in patients receiving teclistamab.

Introduction: Thrombotic thrombocytopenic purpura (TTP) has been previously described in pregnancy, however there is limited data available on the impact of TTP in this subset of patients. In this analysis, we evaluate the maternal and fetal morbidity outcomes of TTP in hospitalized pregnant patients. Methods: We used retrospective data from the National Inpatient Sample (NIS) to identify all hospital admissions of pregnant patients with and without TTP from 2012 to 2021 using ICD-9/10 codes. To describe the impact of TTP on maternal and fetal morbidity, we identified different morbidity indicators using standard Centers for Disease Control and Prevention (CDC) definitions with a particular focus on preeclampsia/eclampsia, thromboembolic events (venous and arterial), other organ failure, maternal morbidity and fetal outcomes including intrauterine growth restriction (IUGR) and fetal loss. To account for the effects of acute TTP during pregnancy versus a history of TTP, we separately analyzed hospitalizations that included plasma therapeutic plasma exchange (TPE). Predictors of maternal/fetal morbidities in pregnant TTP patients were determined using multivariable logistic regression analysis. Results: We identified 7,514,304 pregnancy hospitalizations with a mean age of 29 years. Of these, 234 women had a diagnosis of TTP, with 74 receiving TPE during admission (acute TTP during pregnancy). Compared to pregnancy-related hospitalizations in women without TTP, those with TTP were more likely to be African American, admitted to urban teaching hospitals, have lower income, and have a higher Charlson Comorbidity Index (CCI). Most maternal morbidity outcomes were significantly higher in hospitalizations with TTP as compared to those without TTP including increased eclampsia (2.1% vs 0.08%), acute myocardial infarction (1.7% vs 0.01%, p<0.001), puerperal cerebrovascular disorders (8.1% vs 0.7%, p<0.001), cardiac arrest (0.9% vs 0.01%), acute renal failure (35% vs 0.2%, p<0.001), adult respiratory distress syndrome (ARDS) (6.4% vs 0.06%, p<0.001), disseminated intravascular coagulation (DIC) (18% vs 0.2%, p<0.001), pulmonary edema/acute heart failure (5.1% vs 0.1%, p<0.001), sepsis (9% vs 0.22%, p<0.001), shock (6.4% vs 0.1%, p<0.001), air/thrombotic embolism (3.0% vs 0.05%, p<0.001), blood transfusion requirement (25.6 vs 1.28%, p<0.001), and ventilation requirement (6.4% vs 0.06%, p<0.001). There was also a higher need for cesarean sections in TTP hospitalizations compared to non-TTP (57.1% vs 36.9%). For fetal morbidity outcomes, intrauterine growth restriction (IUGR) was more common in TTP hospitalizations (6.8% vs 2.4%, p<0.001), while there was no statistical difference between the two groups in the rates of preterm delivery (3.9% vs 3.3%, p=0.651). In-hospital mortality (1.7% vs 0.02%, p<0.001), and length of stay (11 vs 3 days, p<0.001) were also significantly higher in hospitalizations with TTP. Patients with TTP who received TPE during the hospital stay had worse maternal morbidity outcomes than those who did not, likely reflecting the active nature of the disease in this cohort. In the multivariate analysis, CCI ≥ 1 (OR 3.52, 95% CI, 1.64-7.54) and receipt of TPE (OR 2.99, 95% CI, 1.52-5.86) were associated with higher likelihood of maternal/fetal morbidity in TTP hospitalizations. Conclusion: In conclusion, TTP has a significant impact on hospitalized pregnant patients, both on maternal and fetal outcomes. Further studies are needed to assess risk factors associated with TTP in pregnancy and ideal treatment regimens for these patients.

Abstract Context Dystonia is a movement disorder that causes involuntary muscle contractions leading to abnormal movements and postures, such as twisting. Dystonia is the third most common movement disorder in the United States, with as many as 250,000 people affected. Because of its complexity, dystonia presents a significant challenge in terms of management and treatment. Despite limited research, osteopathic manipulative treatment (OMT) has been considered as an adjunctive treatment due to its inexpensive and noninvasive nature, as opposed to other modalities such as botulinum toxin injections, deep brain stimulation (DBS), and transcranial magnetic stimulation, which are often expensive and inaccessible. OMT treatments performed in case studies and series such as balanced ligamentous tension/articular ligamentous strain (BLT/ALS), muscle energy (ME), high-velocity low-amplitude (HVLA), and myofascial release (MFR) have shown reduction of pain and muscle hypertonicity, including in patients with dystonia. Objectives The studies reviewed in this paper provide a snapshot of the literature regarding the current evidence of OMT’s role for dystonia. Methods A medical reference librarian conducted a thorough literature search across multiple databases including PubMed and Google Scholar to find articles relevant to the use of OMT for dystonia. The search employed a combination of Medical Subject Headings (MeSH) terms and keywords related to osteopathic medicine and dystonia to ensure precise retrieval of relevant articles within the last 20 years. Despite limited research on the topic, all four relevant reports found in the literature were selected for review. Results Of the four relevant reports, case series and studies highlighted the potential benefits of OMT in managing dystonia, particularly cervical dystonia and foot dystonia. OMT has shown promising results addressing pain, stiffness, and impaired motor function. In cases of foot dystonia in Parkinson’s disease, OMT has helped improve gait and reduce pain by targeting somatic dysfunctions (SDs) associated with dystonia, such as abnormalities in foot progression angle (FPA) and musculoskeletal imbalances. Also, OMT has been found to alleviate symptoms of cervical dystonia, including tremors, muscle spasms, and neck stiffness. These interventions performed in case studies and series led to improvements in gait biomechanics in foot dystonia and overall symptom severity in patients with cervical dystonia. Conclusions Currently, botulinum toxin, oral medications, physical therapy, and rehabilitation are commonly utilized in managing dystonia. The studies reviewed in this paper suggest that these treatments may lead to improvements in pain and muscle hypertonicity in patients with dystonia. It is important to investigate whether factors such as the type of dystonia (eg, focal vs. segmental) and its underlying cause (eg, idiopathic, trauma, infection, autoimmune, medication side effects) influence treatment outcomes. Further research is recommended to explore the role of OMT in managing dystonia.

A 40 year old woman who underwent combined heart-lung transplant for familial severe pulmonary hypertension experienced episodes of nonsustained ventricular tachycardia followed by sudden ventricular fibrillation arrest 8 days after transplant. Postarrest investigations revealed left lower lobe herniation into the right lower hemithorax, prompting emergent reoperation, and hernia reduction. Arrhythmias resolved following reduction of the herniated lung and facilitated rapid weaning from vasopressor and ventilatory support. To our knowledge, this is the first reported case of cardiac arrest due to lung herniation after combined heart-lung transplantation. Herein, we describe this rare presentation and offer insights and management strategies for the cardiac intensivist.