Li, Zhuo

Abstract Objective Molecular breast imaging (MBI) is a supplemental screening modality consistently demonstrating incremental cancer detection over mammography alone; however, its lengthy duration may limit widespread utilization. The study purpose was to assess feasibility of an abbreviated MBI protocol, providing readers with mediolateral oblique (MLO) projections only and assessing performance in lesion detection and localization. Methods Retrospective IRB-exempt blinded reader study administered to 5 fellowship-trained breast imaging radiologists. Independent reads performed for 124 screening MBI cases, half abnormal and half negative/normal. Readers determined whether an abnormality was present, side of abnormality, and location of abnormality (medial/lateral). Abnormal cases had confirmatory biopsy or surgical pathology; normal cases had imaging follow-up ensuring true negative results. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess performance. A false negative result indicated that a reader failed to detect abnormal uptake; a false positive result indicated a reader incorrectly called an abnormality for a negative case. Tests for association included chi-square, Fisher-exact, and analysis of variance. Results Mean reader performance for detecting abnormal uptake: sensitivity 96.8%, specificity 98.7%, PPV 98.8%, and NPV 96.9%. Accuracy in localizing lesions to the medial or lateral breast was 100%. There were no associations in reader performance with reader experience, reader technique, lesion morphology, or lesion pathology. Median lesion size was 1.0 cm (range: 0.4–8.0 cm). All readers correctly identified 97.7% (42/43) of lesions with malignant or elevated risk pathology. Conclusion An abbreviated MBI protocol (MLO images only) maintained high accuracy in lesion detection and localization.

Abstract Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x10 9 /L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

AbstractBackgroundHistologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known.MethodsWe performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly.ResultsHAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%–7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122–755 days). Indications for biopsy were follow‐up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss.ConclusionHAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

Abstract Introduction Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI) based GVHD prophylaxis has shown lower rates of acute and chronic GVHD when compared with the traditional prophylaxis of calcineurin inhibitor (CNI) and methotrexate (MTX) in matched donor (related and unrelated) allo-HCT. The combination of PTCy with sirolimus as a calcineurin inhibitor-free GVHD prophylaxis has shown promising results with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15-27% and 20-27% respectively in patients undergoing matched and haploidentical allo-HCT. We report a single center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy in combination with sirolimus (PTCy/Siro) with those receiving the standard GVHD prophylaxis of tacrolimus and MTX (Tac/MTX). Methods One hundred and sixteen consecutive patients who had undergone a MRD or MUD allo-HCT between January 2018 to January 2021 and received either PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimens were eligible for inclusion. The selection of PTCy with sirolimus or tacrolimus with methotrexate as GVHD prophylaxis regimen was based on physician choice. Primary endpoints were cumulative incidence of acute (grade II to IV) and chronic GVHD. Secondary endpoints were a) neutrophil and platelet engraftment; b) overall survival (OS); c) non-relapse mortality (NRM); d) relapse; e) clinical infections and f) time to immunosuppression (IS) withdrawal. Kaplan-Meier method was used to estimate 1-year and 2-year freedom from long term adverse events, including chronic GVHD, relapse, NRM and OS. All tests were two-sided with alpha level set at 0.05 for statistical significance. Results Out of a total of 116 patients undergoing MRD and MUD allo-HCT, 29 received PTCy/Siro and 87 Tac/MTX. Baseline characteristics were similar between the two arms except patients in PTCy/Siro were younger with median of 48 (range: 24-69) years vs. 61 (range: 20-73) years (p=0.004) in Tac/MTX. There was difference in primary indication for allo-HCT between the two arms with non-hodgkin lymphoma (NHL) being the most common in PTCy/Siro and acute myeloid leukemia (AML) in the Tac/MTX group. Patients receiving PTCy/Siro had a significantly higher median CD3 day 100 chimerism at 100 (90-100) vs. 90 (40-100) % (&lt;0.001) and a significantly shorter median time to IS withdrawal at 138 (37-312) vs 232(66-1120) days for patients receiving Tac/MTX. There was no difference between the two arms for length of hospital stay and time to neutrophil engraftment, but PTCy/Siro had a significantly longer median time for platelet engraftment at 17.5 (12-74) vs.14 (11-38) days (p= 0.001). No significant difference was observed between the two arms for incidence of grade II to IV acute GVHD, grade III to IV acute GVHD, steroid refractory acute GVHD or clinical infections (Table 1). After a median follow up of 1.1 (range: 0-1.8) years, patients receiving PTCy/Siro were significantly less likely to have chronic GVHD with 2-year freedom from GVHD of 75% (95%CI: 58-98%) vs 20% (95%CI 10-40%), p=0.005 (Figure 1). There was no difference between the two arms for OS, disease relapse or non-relapse mortality (Table 2). Conclusion In this study, the combination of PTCy/Siro is associated with a significantly lower risk of chronic GVHD when compared against the traditional GVHD prophylaxis of CNI and methotrexate, despite significantly earlier IS withdrawal. Other long-term outcomes of interest remained comparable between the two arms. Chronic GVHD contributes to significant morbidity and mortality in patients undergoing allo-HCT. Newer strategies to limit the impact of chronic GVHD are needed. The results of our study warrant validation in a large, multicenter, randomized prospective trial. Figure 1 Figure 1. Disclosures Murthy: CRISPR Therapeutics: Research Funding. Foran: gamida: Honoraria; takeda: Research Funding; novartis: Honoraria; trillium: Research Funding; boehringer ingelheim: Research Funding; OncLive: Honoraria; abbvie: Research Funding; certara: Honoraria; sanofi aventis: Honoraria; syros: Honoraria; taiho: Honoraria; revolution medicine: Honoraria; bms: Honoraria; servier: Honoraria; pfizer: Honoraria; actinium: Research Funding; aptose: Research Funding; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding.

AbstractBackgroundHypertrophic cardiomyopathy (HCM) presents with a hypertrophied left ventricle (LV). It is often associated with LV outflow tract obstruction (LVOTO) and a risk for sudden death. This study aimed to describe outcomes of patients with HCM who underwent liver transplant (LT).MethodsA retrospective review was conducted for patients diagnosed with HCM undergoing LT. Patient characteristics, preoperative echocardiography results, HCM risk of sudden cardiac death prediction model score, and 5‐year mortality were examined. A univariable Cox proportional hazards model was used to evaluate the association between risk factors and 5‐year mortality. All tests were two‐sided with the alpha level set at .05.ResultsTwenty‐nine patients were included in the analysis. Six patients (21%) had a perioperative cardiopulmonary complication. The 5‐year survival rate was 61% (95% CI, 45–82). The analyzed risk factors showed that 5‐year post‐LT survival was significantly predicted by maximal LV outflow tract gradient at rest > 60 mmHg (hazard ratio, 1.04 [95% CI, 1.01‐1.06]).ConclusionsPreoperative LV outflow tract resting gradient > 60 mmHg was associated with 5‐year post‐LT mortality. The results suggest the severity of LVOTO identified by echocardiography is a prognostic tool for patients with HCM after LT.

AbstractBackgroundCoccygodynia is a painful condition of the tailbone that occurs more commonly in females. The association of coccyx pain with pelvic floor symptoms and the prevalence of coccyx pain in women with pelvic pain has not previously been reported.ObjectiveTo identify the prevalence of coccygodynia in women with pelvic pain and to describe the association of coccygodynia with pelvic floor examination findings and symptoms.DesignRetrospective cohort analysis.SettingTertiary medical institution.ParticipantsOne hundred twenty‐seven women presenting for outpatient pelvic floor physical therapy treatment who underwent vaginal and rectal pelvic floor examination.Main Outcome MeasuresPrevalence of coccygodynia, pain scores, association of coccygodynia with other comorbidities and diagnoses, and association of coccygodynia with physical examination findings.ResultsSixty‐three (49.6%) of 127 women with pelvic pain presented with coccygodynia and 64 (50.4%) did not. Women with coccygodynia had significantly higher rates of muscle spasm (50.8% vs. 31.2%, p = .025) higher visual analog scale pain scores (median 5 vs. 3, p = .014), higher rates of outlet dysfunction constipation (31.7% vs. 10.0%, p = .032), and higher rates of fibromyalgia (15.9% vs. 3.1%, p = .014). On pelvic examination, women with coccygodynia were significantly more likely to have sacrococcygeal joint hypomobility (65.1% vs. 14.1%, p < .001), coccygeus muscle spasm (77.8% vs. 17.2%, p < .001), anococcygeal ligament pain (63.5% vs. 9.4%, p < .001), external anal sphincter pain/spasm (33.3% vs. 13.1%, p < .001), and impaired pelvic floor muscle coordination (77.8% vs. 57.8%, p = .016).ConclusionsAlmost 50% of women seeking pelvic floor physical therapy for pelvic pain had coexisting coccygodynia. These women had higher pain scores, increased pelvic floor dysfunction, and significantly greater abnormal physical exam findings. This study demonstrates a strong link between coccygodynia, pelvic floor symptoms, and pelvic pain and highlights the importance of screening for and identifying coccyx pain when evaluating women with pelvic pain.

Background Surgical resection is the curative treatment for all subtypes of cholangiocarcinoma (CCA), including intrahepatic, hilar/peri-hilar, and distal. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival. Methods A retrospective cohort study was performed for patients who underwent surgical resection for CCA at our institution from 1995 to 2016. Demographics, operative variables between CCA tumors, and postoperative complications were analyzed. Predictors of overall and recurrence-free survival were determined via statistical analysis. Results A total of 170 patients with a mean age of 61 years old underwent surgical resection of intrahepatic (n = 64, 37.6%), hilar/peri-hilar (n = 75, 44.1%), and distal (n = 31, 18.2%) CCA. Operations performed included liver resections (n = 83, 48.8%), liver transplants (n = 56, 32.9%), and pancreaticoduodenectomies (n = 31, 18.2%). The overall survival rate at 1, 5, and 10 years was 81.1%, 32.4%, and 17.2%, respectively. Low pathological stage and negative resection margins were associated with lower recurrence and higher survival rates. Tumor location and the type of operation performed were not predictive of recurrence or OS in this cohort. Discussion This study shows that definitive surgical resection with negative margins can result in long-term survival even at 10 years. Small tumor size and low pathological stage are predictive of higher survival rates post-surgery, emphasizing the importance of early diagnosis and appropriate surgical treatment in achieving positive outcomes.

AbstractPurposeInduction immunosuppression has improved the long‐term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR).MethodsSixty‐seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR‐received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA.ResultsDe novo HLA DSA were detected in 22/67 (32.8%) LTR within 1‐year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant.ConclusionInduction immunosuppression utilizing a modified regimen of single‐dose rATG is associated with a significant reduction in de novo DSA production in LTR.

Abstract Introduction/Aims Cortical hyperexcitability is a feature of amyotrophic lateral sclerosis (ALS) and cortical excitability can be measured using transcranial magnetic stimulation (TMS). Resting motor threshold (MT) is a measure of cortical excitability, largely driven by glutamate. Perampanel, a glutamate α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptor blocker, is predicted to increase the cortical excitability threshold. This study aimed to evaluate TMS to functionally assess target engagement in a study of perampanel in ALS. Method We studied the MT of ALS patients randomized to a single dose of perampanel or placebo 5:1 hourly for 4 h. Twelve patients participated at 4 mg and 7 returned for dosing and retesting at 8 mg. The study was terminated in April 2020 due to coronavirus disease 2019‐related restrictions, after 7 out of 12 planned patients had received the 8 mg dose. Serum concentrations were also measured. Results Ten patients received the 4 mg dose (2 received placebo) and 5 received the 8 mg dose (2 received placebo). Motor Threshold increased at 2 h after dosing in the combined treatment group +7% of maximal stimulator output ( P < .01). Change could be detected in the larger 4 mg group ( P = .02), but not in the smaller 8 mg dose group ( P = .1). No side effects were reported after single dose exposure. Discussion This study shows that perampanel effects the physiology of upper motor neurons. Studies aiming at gauging the effect of perampanel on ALS disease progression are already ongoing. Motor threshold may serve as a marker of biological target engagement.