Citations

580 Background: Patients (pts) in Cohort A of the American College of Surgeons Oncology Group Z1031 (Alliance) trial of NET for cStage II-III breast cancer were randomized to anastrozole [ANA], letrozole [LET] or exemestane [EXE] for 16-18 weeks (wks). In Cohort B, pts chose between ANA and LET and switched to chemotherapy or surgery if a tumor biopsy after 2-4 wks of NET had Ki67 >10%. Treatments after surgery were not defined by the trial protocol. SET2,3 measures nonproliferation gene expression related to estrogen and progesterone receptors adjusting for a baseline prognostic index that combines clinical tumor and nodal stage and a 4-gene molecular subtype (RNA4) defined by ESR1, PGR, ERBB2 and AURKA. High SET2,3 in a pre-treatment biopsy using cStage information is defined as SET2,3 >1.77. Methods: 379 pts had gene expression data from a research tumor biopsy prior to NET (Agilent 44K microarrays). A bioinformatician blinded to pt treatment and clinical outcomes determined SET2,3. The trial statistician then examined the association between SET2,3 and pharmacodynamic response at 2-4 wks (N=141, Cohort B): Ki67 ≤10% and complete cell cycle arrest (CCCA Ki67 ≤2.7%); pathologic outcomes in pts who completed NET: ypStage 0/1 (N=329, Cohorts A&B), PEPI-0 rate (N=155, Cohort B); and event-free survival (EFS) post-registration (N=244, Cohorts A&B). We used Fisher’s exact tests to assess whether responses, and Cox modeling to evaluate whether EFS, differed with respect to SET2,3 status. Results: High SET2,3 in 48% of pts (183/379) was associated with older age (median: 66 vs 63 years; p=0.012); cStage II (95% vs 75%; p <0.001); and pre-NET Ki67 ≤10% (37% vs 20%; p< 0.001) in pts with low SET2,3. In Cohort B, pts with high SET2,3 had a higher rate of pharmacodynamic response in their tumor at wk 2-4 than pts with low SET2,3 (Table). In the subset of Cohort B pts with wk 2-4 Ki67 ≤10%, pre-treatment SET2,3 trended numerically higher in pts who achieved PEPI-0 score (p=0.049) but the proportion achieving PEPI-0 did not differ by SET2,3 high/low status (Table). EFS was significantly longer for pts with high SET2,3 than pts with low SET2,3 (HR[H/L]: 0.52; 95% CI: 0.34-0.80; p=0.003). Conclusions: An exploratory analysis of Z1031 data demonstrated that the rate of pharmacodynamic suppression of proliferation by NET at 2-4 wks was greater and EFS was longer for pts with breast cancer expressing high SET2,3 disease than pts with low SET2,3. Support: U10CA180821, U10CA180882, U24CA196171; https://acknowledgments.alliancefound.org ; Clinical trial information: NCT00265759. [Table: see text]

Purpose: New-onset persistent diplopia has become a common complication after glaucoma drainage device (GDD) placement. Understanding the orbital anatomy of such patients may provide information regarding risk of diplopia, GDD selection, and post-operative management. The purpose of this study was to examine the orbital anatomic differences in diplopic and non-diplopic patients after GDD implantation using high-resolution MRI. Methods: Seven eyes ( N = 4 with diplopia and N = 3 without diplopia after GDD placement) of seven patients that had undergone placement of Baerveldt 250 (B250), Baerveldt 350 (B350), or Ahmed FP7 (FP7) GDD were prospectively enrolled at a single institution. All patients underwent a 3.0T orbital MRI with 3D volumetric T1 and T2 weighted sequence. Images were analyzed for orbital volume, axial length, orbital distances, presence of superior rectus-lateral rectus (SR-LR) band, position of GDD, and SR-LR angles. Results: Patients with diplopia had smaller mean ± SD orbital axial (911.5 ± 111.8 mm 3 vs 931.7 ± 79.7 mm 3 ) and coronal volumes (1162.5 ± 145.5 mm 3 vs 1180 ± 34.6 mm 3 ) compared to non-diplopic patients. Average orbital rim distances were larger for the diplopic group. The SR-LR displacement angle for diplopic patients was larger (101.6° ± 8.1 vs 94.7° ± 17.6) while the SR-LR quadrantic angle (86.6° ± 4.2 vs 89.1° ± 4.3) was smaller. SR-LR band was present and intact in all patients. GDD malpositioning was not evident in any patient. Conclusion: The decreased orbital axial and coronal volumes as well as increased orbital rim distances in diplopic patients suggests the need for further studies to understand the role of orbital anatomy in occurrence of diplopia. Dynamic MRI imaging may be helpful in identifying differences in extraocular muscle function that reveal an etiology of diplopia in patients with GDD implantation.

Abstract Introduction: The inconsistent use of standardized approaches for classifying postamputation pain (PAP) has been a barrier to establishing its prevalence. Objectives: The primary objective of this systematic review and meta-analysis is to determine the prevalence of nontraumatic lower-extremity PAP using an established taxonomy. The secondary objective is to determine the prevalence of PAP subtypes, including phantom limb pain and residual limb pain (RLP). Methods: An a priori protocol was registered, and a database search was conducted by a reference librarian. Randomized trials and uncontrolled studies were eligible for inclusion. The risk of bias was assessed using a tool developed for uncontrolled studies. A total of 2679 studies were screened, and 13 studies met inclusion criteria (n = 1063). Results: The sources of risk of bias included selection bias and, to a lesser extent, whether the outcome was adequately ascertained. Two studies reported the prevalence of PAP and the pooled prevalence was 61% (95% confidence interval [CI], 33%–86%) with high heterogeneity (I2 = 93%). Thirteen studies reported the prevalence of phantom limb pain and the pooled prevalence was 53% (95% CI, 40%–66%) with high heterogeneity (I2 = 93%). Eight studies reported the prevalence of RLP and the pooled prevalence was 32% (95% CI 24%–41%) with high heterogeneity (I2 = 76%). Clinical subtypes of RLP were not reported. Conclusions: The prevalence of PAP is high in patients with nontraumatic lower-extremity amputations. Ongoing research that uses a taxonomy for PAP is needed to fully delineate the prevalence of PAP subtypes.

Abstract Dermal filler injections, one of the most commonly performed procedures in facial esthetic surgery, are rising in popularity. This has also led to an increase in nonmedical grade filler injections performed by nonmedical personnel, including that of injectable silicone. Surgical removal of silicone fillers is challenging, as the hydrophobic material often disperses within the soft tissue as droplets. This can lead to a systemic inflammatory reaction requiring steroid treatment. MRI localization of the filler material does not enable intraoperative guidance, and palpitation of the material is challenging since the filler droplets are often too small to palpate and located in multiple planes. We present a case demonstrating the advantages of utilizing intraoperative ultrasound to localize and silicone filler material. Utilizing this technique, we were able to achieve a high degree of excision of silicone filler material and the patient was able to stop her previous necessary immunosuppressive steroid regimen successfully.

Objective Haemorrhoidal disease (HEM) affects a large and silently suffering fraction of the population but its aetiology, including suspected genetic predisposition, is poorly understood. We report the first genome-wide association study (GWAS) meta-analysis to identify genetic risk factors for HEM to date. Design We conducted a GWAS meta-analysis of 218 920 patients with HEM and 725 213 controls of European ancestry. Using GWAS summary statistics, we performed multiple genetic correlation analyses between HEM and other traits as well as calculated HEM polygenic risk scores (PRS) and evaluated their translational potential in independent datasets. Using functional annotation of GWAS results, we identified HEM candidate genes, which differential expression and coexpression in HEM tissues were evaluated employing RNA-seq analyses. The localisation of expressed proteins at selected loci was investigated by immunohistochemistry. Results We demonstrate modest heritability and genetic correlation of HEM with several other diseases from the GI, neuroaffective and cardiovascular domains. HEM PRS validated in 180 435 individuals from independent datasets allowed the identification of those at risk and correlated with younger age of onset and recurrent surgery. We identified 102 independent HEM risk loci harbouring genes whose expression is enriched in blood vessels and GI tissues, and in pathways associated with smooth muscles, epithelial and endothelial development and morphogenesis. Network transcriptomic analyses highlighted HEM gene coexpression modules that are relevant to the development and integrity of the musculoskeletal and epidermal systems, and the organisation of the extracellular matrix. Conclusion HEM has a genetic component that predisposes to smooth muscle, epithelial and connective tissue dysfunction.

Background Diffuse intracranial susceptibility abnormalities have recently been described among patients with coronavirus disease 2019 (COVID-19), although prior studies have consisted of case reports and/or series. This brief literature review seeks to compile and catalogue the available data to elucidate characteristic features of such findings. Materials and methods Scientific articles and studies on intracranial microhemorrhages in the setting of COVID-19 were searched on PubMed, Google Scholar, and the Cochrane Library. Included studies described intracranial microbleed(s) on magnetic resonance imaging in patients with COVID-19. If multiple patients were described, only patients with intracranial microhemorrhage on magnetic resonance imaging were included for analysis. Patient demographics, severity of illness (e.g. intensive care unit admission and/or intubation), time from diagnosis of COVID-19 to magnetic resonance imaging, and location(s) of any observed microhemorrhages were noted. Results A total of 39 patients with suspected intracranial microhemorrhages have been described in prior studies. The average age of patients was 64.7 years; 21.9% were women. The average time between COVID-19 diagnosis and magnetic resonance imaging was 31.7 days. All patients in the cohort were admitted to critical care and were either intubated or treated with extracorporeal membrane oxygenation during their clinical course. Microhemorrhages were most commonly located in the subcortical/juxtacortical white matter and corpus callosum. Conclusions Intracranial microbleeds are a well-documented finding in patients with severe COVID-19, and are most commonly callosal and subcortical/juxtacortical in location.

Abstract Spinal cord stimulation (SCS) is used to treat a variety of chronic pain conditions refractory to more conservative management including refractory angina pectoris. We identified 31 patients who underwent SCS implantation for the indication of refractory angina at a single institution from 2003 through 2018. Sixteen patients were male, and 15 were female. Average age was 53.9 years. Prior to SCS implantation, all patients had at least one coronary angiogram. Ten (32.3%) patients had undergone percutaneous coronary intervention, and four (12.9%) had undergone coronary artery bypass grafting. Thirty patients (96.7%) were currently using anti-angina medications. Twenty-six patients (83.9%) were on antiplatelet or anticoagulant agents at the time of SCS evaluation. Spinal cord stimulation implanters must perform a comprehensive evaluation incorporating appropriate multidisciplinary care particularly in patients with refractory angina given their cardiovascular comorbidities. It is important to have baseline data (e.g., pain scores, nitroglycerin consumption, frequency of angina episodes, and a questionnaire, such as the Seattle Angina Questionnaire) to compare with follow-up data to help define treatment success. We report a single institution’s pre-operative experience for patients undergoing SCS for refractory angina to illustrate unique pre-operative SCS considerations in this chronic pain population.