Citations

In mammals, breathing requires an inspiratory pump to generate a negative intrathoracic pressure and thus pull air into the lungs for gas exchange. Exclusively in mammals, the diaphragm muscle (DIAm) is the major inspiratory pump, which separates the thoracic and abdominal cavities. With DIAm contraction, a negative intrathoracic and positive abdominal pressure are generated [i.e., transdiaphragmatic pressure (P di )]. During breathing, the DIAm is very active, with a duty cycle (time active vs. inactive) similar to that of the heart. Like the heart, this is a pump that cannot fail! Thus, in controlling breathing, the nervous system must activate DIAm to accomplish pump function while avoiding fatigue. The timing of DIAm activations must also be coordinated with activation of the upper airway muscles (the pipes) to avoid airway occlusion and aspiration and the intercostal and abdominal muscles to appropriately stiffen the body cavities. Similarly, neural control and coordination of the DIAm in nonventilatory behaviors (airway protection, swallowing, vocalization, and voiding) are equally complex, with coordinated activation of the DIAm and abdominal muscles. It is becoming increasingly clear that impaired nonventilatory functions underlie the pathophysiology of a variety of medical conditions. In this review, we will delve into the detailed mechanistic underpinnings of the neural control of the DIAm and the symphonic coordination of its activation during breathing and other behaviors. We will attempt to move the field from considering the DIAm only as an inspiratory pump, emphasizing neural control of airway, intercostal, and abdominal muscles that must be coordinated with DIAm activation.

Background: Obstructive Sleep Apnea (OSA) is a common occurrence in the perioperative patient population but is often undiagnosed. Point-of-Care Ultrasound (POCUS) has emerged as a promising tool for perioperative assessment; however, its effectiveness in detecting the presence or severity of OSA needs to be evaluated. Objective: We assessed the ability of airway POCUS as a screening and severity evaluation tool for OSA by examining its correlation with STOP-BANG scores and the Apnea–Hypopnea Index (AHI). Design: Cross-sectional observational study. Setting: A single-center study in a tertiary care hospital between June 2020 to May 2021. Patients: Adult patients aged 18–65 with prior Polysomnography (PSG) for OSA workup were screened. Interventions: The participants completed the STOP-BANG questionnaire and subsequently underwent POCUS examinations, either pre- or post-surgery. Ten different POCUS views previously used for evaluating OSA were acquired in a predefined sequence, with subsequent measurements of airway parameters. Outcome measures: Generalized linear modeling was used to explore and assess the relationships between the measured parameters, STOP-BANG, and AHI scores (modeled continuously and categorized into risk levels of STOP-BANG and AHI). Results: A total of 260 patients were screened, of which 142 were enrolled and 127 completed the scanning studies. The median AHI was 16.71, while the STOP-BANG scores were mostly between 5 and 6, indicating a moderate-to-high OSA risk in the study population. Notably, only neck circumference was significantly associated with AHI severity (p = 0.012), whereas none of the other POCUS measures were. Among the POCUS measures, significant associations with STOP-BANG scores were observed for the Tongue Cross-Sectional Area (T-CSA) (p = 0.002), Retro-Palatal Diameter (RPD) (p = 0.034), Distance Between Lingual Arteries (DLA) (p = 0.034), and Geniohyoid Muscle Thickness (GMT) (p = 0.040). Conclusions: Neck circumference is a more reliable predictor of OSA severity (AHI) compared to other POCUS measurements. Many of the POCUS measures had a good correlation with the STOP-BANG scores, highlighting the utility of POCUS as a screening tool for OSA rather than as a severity evaluation tool.

Abstract Background The CCDC26 germline variant rs55705857 is causal for development of IDH mutant (IDHmut) adult glioma. However, ~60% of IDHmut patients do not carry the rs55705857 risk allele. We aimed to identify variants associated with developing IDHmut glioma among patients that do not have the rs55705857 risk allele and to further understand development of IDHwt glioma. Methods We used three datasets that included 1216 IDHmut and 1442 IDHwt glioma patients and a case–case design to perform genome-wide association (GWAS) analyses comparing IDHmut versus IDHwt glioma. Analyses were performed overall and stratified by rs55705857 genotype and sex. Multivariable logistic regression and regression trees were used to develop models to predict IDH status using germline variants, age, and contrast enhancement on MRI. Results Three regions were identified comparing IDHmut versus IDHwt: rs55705857 (meta P-value [P] = 1.35 × 10−43), PHLDB1 (rs7125115, P = 3.46 × 10−17), and D2HGDH (rs71430382, P = 2.43 × 10−12). When analyzing only patients that do not have the rs55705857 risk allele, PHLDB1 (rs7125115, P = 1.73 × 10−13) and D2HGDH (rs71430382, P = 8.86 × 10−10) were identified. Among patients who have the rs55705857 risk allele, four variants between ROBO1 and ROBO2 (rs4680975, P = 4.65 × 10−7) increased the likelihood of having an IDHwt tumor. Tumor expression of ROBO1 was associated with rs4680975 genotype in IDHwt patients that have the rs55705857 risk allele (P = 0.034). Multivariable logistic analysis demonstrated that rs55705857, rs71430382 (D2HGDH), and age predicted IDH mutation status. Conclusions To understand the development of adult glioma, we demonstrate that D2HGDH and PHLDB1 should be prioritized for functional studies in IDHmut tumors. The ROBO1 region warrants further investigation in IDHwt tumors.

We report 3-year follow-up results from TRANSFORM comparing lisocabtagene maraleucel (liso-cel) versus standard of care (SOC) for second-line primary refractory/early relapsed (≤12 months) large B-cell lymphoma (LBCL). Adults eligible for autologous stem cell transplantation (N = 184) were randomly assigned 1:1 to liso-cel (100 × 10 6 chimeric antigen receptor–positive T cells) or SOC. Results are reported descriptively. With a median follow-up of 33.9 months, median (95% CI) event-free survival was 29.5 months (9.5 to not reached [NR]) for liso-cel versus 2.4 months (2.2 to 4.9) for SOC (hazard ratio [HR], 0.375; 95% CI, 0.259 to 0.542). Median progression-free survival was NR (12.6-NR) for liso-cel versus 6.2 months (4.3-8.6) for SOC (HR, 0.422; 95% CI, 0.279 to 0.639) with 36-month rates of 51% versus 26.5%. Median overall survival (OS) was NR for both arms (HR, 0.757; 95% CI, 0.481 to 1.191), with 66% of patients crossing over to receive liso-cel; 36-month OS rate was 63% for liso-cel versus 52% for SOC. OS HR (0.566 [95% CI, 0.359 to 0.895]) favored liso-cel when accounting for the treatment effect of crossover. Safety results were consistent with previous reports. At 3-year follow-up, liso-cel confirmed superior, more durable efficacy versus SOC with a favorable safety profile and no new safety signals. These data support liso-cel as an effective second-line treatment with curative potential for relapsed/refractory LBCL.

BACKGROUND AND OBJECTIVES: Gynecological cancers represent 10% to 15% of cancers in women, but brain metastases (BM) are uncommon, with limited evidence regarding their management. This study investigates the role of stereotactic radiosurgery (SRS) for BM from primary gynecological cancers. METHODS: Institutions of the International Radiosurgery Research Foundation participated in this study. Inclusion criteria required histological diagnosis of epithelial ovarian, cervical, or endometrial cancer, SRS between 2000 and 2020, and at least 1 imaging or clinical follow-up. RESULTS: A total of 276 patients having SRS for 977 BM were included. Median age at SRS was 62 years (IQR, 55-70). Primary cancer origin was ovarian in 128 (46%), cervical in 43 (16%), and endometrial in 105 patients (38%). Median Karnofsky Performance Scale was 80%, and systemic disease was active in 124 (45%) of patients. A median of 1 metastasis was treated (IQR, 1-3) per patient. Median individual metastasis volume was 0.27 cc (IQR, 0.05-1.59 cc). The majority (91%) received single-fraction SRS, using a median margin dose of 18 Gy (IQR, 16-20 Gy). Actuarial overall survival was 77%, 65%, and 44% at 6, 12, and 24 months, respectively. Predictors of worsened survival included older age, cervical and endometrial primary, previous whole-brain radiation therapy (WBRT), active systemic disease, worsened Karnofsky Performance Scale, absence of subsequent surgery, and increasing number of BM. Actuarial local control was 94% at 6 months, 89% at 12 months, and 78% at 24 months. Previous SRS or WBRT, tumor bed treatment, and cervical histology increased the risk of local failure. New remote BM and leptomeningeal dissemination occurred in 44% and 11% of patients, respectively. Adverse radiation effects (ARE) occurred in 13% of cases but were symptomatic in only 3%. Previous WBRT or SRS and increased tumor diameter increased the risk of ARE. CONCLUSION: SRS is an effective management for BM from gynecological cancers with low risks of symptomatic ARE.

Aberrant internal carotid artery (ICA) is a vascular anomaly in which a segment of the ICA courses through the middle ear. The association of aberrant ICAs and pseudoaneurysm formation is not well known and can be an important finding to recognize on imaging. In this series, we present three cases of aberrant ICAs having asymmetric contour deformities consistent with pseudoaneurysms diagnosed utilizing CT of the temporal bone.

Abstract Clinicians struggle to accurately classify biliary strictures as benign or malignant. Current endoscopic retrograde cholangiopancreatography (ERCP)-based sampling modalities including brush cytology and forceps biopsy have poor sensitivity for pathologic confirmation of malignancy. Cholangioscopy allows for direct visualization and sampling of biliary pathology; however, this technology is also associated with inaccurate classification of biliary disease. Previously, an artificial intelligence (AI) system that analyzes cholangioscopy footage was found to be more accurate in diagnosing biliary malignancy than ERCP sampling techniques. The aim of this study was to validate this AI system on a new series of examinations. Three academic centers collected all available unedited cholangioscopy recordings. The videos were processed by the cholangioscopy AI system. After analyzing videos, the AI system provided predictions as to whether malignancy was present. AI performance in classifying strictures was compared with the performance of brush cytology and forceps biopsy. 112 cholangioscopy examinations (containing 4 817 081 images) were generated from 99 patients. Of those examinations, 61 (54.5%) were for investigation of biliary strictures (31 [50.8%] benign, 30 [49.2%] malignant). For the correct classification of strictures, the AI system was 80.0% sensitive and 90.3% specific. It was also significantly more accurate for stricture classification (85.2%) than brush cytology (52.5%; P<0.001), forceps biopsy (68.2%; P=0.04), and the combination of brush cytology and forceps biopsy (66.7%; P=0.02). A previously developed cholangioscopy AI system was found to continually outperform standard ERCP sampling modalities for accurate identification of malignancy, without additional retraining, in a multicenter validation cohort.