Citations

BACKGROUND: Chronic entrapment neuropathy results in a clinical syndrome ranging from mild pain to debilitating atrophy. There remains a lack of objective metrics that quantify nerve dysfunction and guide surgical decision-making. Mechanomyography (MMG) reflects mechanical motor activity after stimulation of neuromuscular tissue and may indicate underlying nerve dysfunction. OBJECTIVE: To evaluate the role of MMG as a surgical adjunct in treating chronic entrapment neuropathies. METHODS: Patients 18 years or older with cubital tunnel syndrome (n = 8) and common peroneal neuropathy (n = 15) were enrolled. Surgical decompression of entrapped nerves was performed with intraoperative MMG of the hypothenar and tibialis anterior muscles. MMG stimulus thresholds (MMG-st) were correlated with compound muscle action potential (CMAP), motor nerve conduction velocity, baseline functional status, and clinical outcomes. RESULTS: After nerve decompression, MMG-st significantly reduced, the mean reduction of 0.5 mA (95% CI: 0.3-0.7, P < .001). On bivariate analysis, MMG-st exhibited significant negative correlation with common peroneal nerve CMAP ( P < .05), but no association with ulnar nerve CMAP and motor nerve conduction velocity. On preoperative electrodiagnosis, 60% of nerves had axonal loss and 40% had conduction block. The MMG-st was higher in the nerves with axonal loss as compared with the nerves with conduction block. MMG-st was negatively correlated with preoperative hand strength (grip/pinch) and foot-dorsiflexion/toe-extension strength ( P < .05). At the final visit, MMG-st significantly correlated with pain, PROMIS-10 physical function, and Oswestry Disability Index ( P < .05). CONCLUSION: MMG-st may serve as a surgical adjunct indicating axonal integrity in chronic entrapment neuropathies which may aid in clinical decision-making and prognostication of functional outcomes.

Background: Abortion is a spontaneous loss of pregnancy before 20 weeks. Approximately 42 million pregnancies end in abortion. The maternal infections that are transmissible from mother to fetus are caused by many pathogens, of which the TORCH complex contributes majorly to neonatal and infant deaths globally. The aim of this study is to detect the prevalence and types of infectious causes of abortion. One hundred aborted women admitted to King Faisal Medical Complex Maternity Hospital in Taif City between the period of 2018 and 2020 were enrolled in this study. The serological test reports (TORCH panel), as well as reports of hematological (CBC) and chemical parameters, were obtained from laboratory management system databases, reviewed, and then analyzed. The H&E-stained microscopic slides of their product of conception (POC) were examined under a microscope and compared with histopathological reports. The prevalence of TORCH infections was 8% in aborted women. Hepatitis B virus (HBV) and mixed TORCH infections constituted the highest percentage of TORCH pathogens in aborted women, constituting 6%. The most detected histopathological finding in seropositive cases (50%) was POC, with mixed inflammatory infiltrates and chronic endometritis, while in seronegative aborted women, POC was normal (64.1%). There is a statistically significant increase in the mean count of white blood cells in seropositive women. Therefore, it is important to provide health campaigns to bring awareness to the population about the risk factors of infectious agents to be avoided, especially during pregnancy.

Abstract The receptor tyrosine kinase AXL is a member of the TYRO3, AXL, and proto-oncogene tyrosine-protein kinase MER family and plays pleiotropic roles in cancer progression. AXL is expressed in immunosuppressive cells, which contributes to decreased efficacy of immunotherapy. Therefore, we hypothesized that AXL inhibition could serve as a strategy to overcome resistance to chimeric antigen receptor T (CAR T)–cell therapy. To test this, we determined the impact of AXL inhibition on CD19-targeted CAR T (CART19)–cell functions. Our results demonstrate that T cells and CAR T cells express high levels of AXL. Specifically, higher levels of AXL on activated Th2 CAR T cells and M2-polarized macrophages were observed. AXL inhibition with small molecules or via genetic disruption in T cells demonstrated selective inhibition of Th2 CAR T cells, reduction of Th2 cytokines, reversal of CAR T-cell inhibition, and promotion of CAR T-cell effector functions. AXL inhibition is a novel strategy to enhance CAR T-cell functions through two independent, but complementary, mechanisms: targeting Th2 cells and reversing myeloid-induced CAR T-cell inhibition through selective targeting of M2-polarized macrophages.

A 41-year-old female with hyperlipidemia presented with typical exertional angina, dyspnea, and pre-syncope of 6 months duration. Physical examination was unremarkable. ECG showed low voltage QRS (Figure A), and Chest CTA was negative for obstructive-CAD, pulmonary emboli, aortic, and lung disease. Cardiac MRI was negative for myocarditis/pericarditis . Resting TTE was unremarkable with normal systolic and diastolic function. NT-Pro BNP, hs-CRP, serum/ urine protein electrophoresis, and free light chains ratio were normal. Regadenoson PET myocardial perfusion test showed a medium-sized area of stress-induced ischemia in mid/apical segments (Figure B) . Resting right heart Cath showed mean RA pressure (9mmHg) and RVEDP (10mmHg), mean PA pressure (19mmHg), and PCWP (15mmHg) with large v-waves, PCWP increased to 28mmHg with limited supine bike exercise, diagnostic of HFpEF (Figure C) . Angiography showed normal coronary arteries while coronary reactivity testing was diagnostic of severe epicardial and microvascular endothelial dysfunction (60% mid/distal LAD constriction and 19% decreased blood flow in response to intracoronary (IC) acetylcholine), and endothelial-independent microvascular dysfunction (coronary flow reserve 2.4 in response to IC adenosine), diagnostic of HFpEF due to coronary endothelial and microvascular disease (Figure D) . The patient’s symptoms improved at 2 weeks follow-up after initiation of furosemide, diltiazem, isosorbide mononitrate, and atorvastatin.

Abstract BACKGROUND: Multiple Myeloma (MM) is an incurable disease with no known germline high penetrant risk gene. The higher risk of MM among affected relatives suggests a genetic contribution to the etiology. To date, 24 common risk variants with low effect sizes were identified using genome-wide association studies, which account for 17% of heritability. However, a systematic analysis of the known rare alleles in cancer predisposition genes has not been undertaken so far in MM. We collaborated with six other academic centers across the United States to identify and select cases for analysis of germline predisposition of MM. METHODS: We performed whole exome, next-generation sequencing of 2,387 familial or early onset germline MM cases from the myeloma sequencing consortium (MMSEQ). We called 1.5 million variants and performed standard quality control of the data. We also obtained exome data on 1,285 cases from UK Biobank (UKBB) and 344,513 non-cancer controls (total=3,672 cases). We analyzed the ultra-rare, coding variants in 90 clinically relevant or putative candidates for cancer predisposition. We then used the automated variant curator PathoMAN to annotate and assert pathogenicity of each variant. We contrasted our results with assertions of pathogenicity from ClinVar and tested for gene association with MM. RESULTS: Overall, we observed several pathogenic or likely pathogenic variants, both singleton and recurrent founder mutations. In the MMSEQ, 8.7% of MM cases harbored a pathogenic variant in these known/putative cancer predisposition genes. Predominant group of pathogenic variants were observed within CHEK2 (19%), TP53 (8%), and ATM (5%). A case-control analysis revealed strong association with TP53 and weakly with ATM. In the familial/early onset MMSEQ cases, TP53 mutations were enriched 68 times more than in the UKBB controls. Our preliminary results suggest that known genes of cancer susceptibility such as TP53 and ATM may also play a role in myeloma risk. CONCLUSION: In a large study of multi-center MM cases, we identified a significant proportion of individuals who are carriers of known (solid) cancer predisposition genes. This study suggests that these known cancer predisposition genes may be relevant in a subset of MM cases. Citation Format: Michael T. Conry, Nicola Camp, Celine Vachon, Michelle Hildebrandt, Elizabeth E. Brown, Steven M. Lipkin, Judy Garber, Susan L. Slager, Samantha Stokes, Aaron D. Norman, Aalin Izhar, Sita Dandiker, Kylee Maclachlan, Kenneth Offit, Saad Usmani, Vijai Joseph. Pathogenic germline mutations and risk of multiple myeloma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5229.