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Background. Surgical-site infections (SSIs) are common in liver transplant recipients. The optimal SSI antimicrobial prophylaxis agent and duration are not established. We aimed to explore risk factors for SSIs after transplant, with a particular interest in the impact of perioperative antibiotic regimen on the development of SSIs. Methods. Retrospective study of adults undergoing liver transplant across 3 transplant programs between January 1, 2020, and June 01, 2021. Results. Of 557 patients included in the study, 32 (5.7%) were infected or colonized with a multidrug-resistant organism (MDRO) within 1 y before liver transplant. Narrow-spectrum SSI prophylaxis with ceftriaxone or cefazolin alone was administered in 488 of 577 patients (87.6%); the remaining 69 patients (12.4%) received broad-spectrum prophylaxis with vancomycin and aztreonam (n = 40), piperacillin–tazobactam (n = 11), carbapenems (n = 8), ceftriaxone and another antibiotic (n = 7), and others. Patients with pretransplant MDRO were more likely to receive broad-spectrum coverage than those without pretransplant MDROs (28.1% versus 11.4%, P = 0.005). SSIs were identified in 40 patients (7.2%); 25 (62.5%) were organ–space infections, 3 (7.5%) were deep incisional infections, and 12 (30.0%) were superficial incisional infections. The median time from liver transplant to SSIs was 14 d (interquartile range, 10–20.2). MDROs were identified in 12 SSIs (30%). Multivariable analysis revealed no significant association between antimicrobial spectrum and risk of SSIs (P = 0.5), whereas surgical leak (P<0.001) and reoperation (P = 0.017) were independently associated with increased risk of SSIs. SSIs were not significantly associated with composite risk of death or liver allograft failure. Conclusions. The spectrum of antimicrobial prophylaxis did not impact the development of SSIs in liver transplant recipients.

BACKGROUND Several studies have highlighted the poor outcomes observed among patients with relapsed/refractory multiple myeloma (MM), particularly those with triple-class refractory (TCR; refractory to at least one PI, one IMiD, and one anti-CD38 mAb) disease. The aim of this study was to describe the longitudinal changes in quality of life (QOL) and other patient-reported outcomes (PROs) among TCR MM patients in real-world clinical practice who initiate a new line-of-therapy. METHODS A prospective, multi-site observational study of patients with TCR MM was conducted through the Mayo Clinic system. Patients initiating a new post-TCR therapy (defined as the index date) were followed for a 12-month observation period during which PRO surveys were administered for the first 6 months. For patients initiating a CAR-T therapy, a survey assessment was conducted at apheresis, lymphodepletion chemotherapy, and every month after T-cell infusion until Month 6. All other patients received a survey assessment before index and then every month thereafter until Month 6. PRO measures included the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30; including the Global Health Score [GHS]), the EORTC Multiple Myeloma Questionnaire (QLQ-MY20; including the Disease Symptoms [DS] domain score), the EORTC QLQ for Chemotherapy-Induced Peripheral Neuropathy (CIPN20), the EuroQoL-5 Dimensions (EQ-5D), the Patient Global Impression of Severity (PGIS), and the Patient Global Impression of Change (PGIC). Patient surveys were supplemented with retrospective chart reviews conducted 3 months and 12 months following the index date to obtain clinical information. Descriptive data were reported at each timepoint separately for patients who received CAR-T and non-CAR-T index therapies. The study is ongoing and this abstract reflects all patient visit data as of April 2023. RESULTS N=55 patients (60% male, 96% White, mean age 66 years) were included in this interim analysis. The median time interval between becoming TCR and the index date was 3.9 months (interquartile range [IQR]: 1.7, 15.5). Most patients had an ECOG score of 0 or 1 (53% and 38%, respectively) and were R-ISS I or II (36% and 54%, respectively); 53% of patients had high-risk cytogenetics and 20% had extramedullary disease. The median (IQR) number of prior treatment lines was 4 (4.0, 5.5). N=24 patients initiated a CAR-T therapy as their index therapy (equally split between ide-cel and cilta-cel); the remaining N=31 patients predominantly initiated a treatment regimen containing an IMiD (52%), a PI (55%), an anti-CD38 antibody (13%), or an alkylating agent (36%). Among CAR-T patients, QOL and disease-related symptoms worsened from baseline through Month 2-3 (eg, mean GHS was 65.9 at apheresis, 64.9 at lymphodepletion, and 53.3 at Month 2 [higher scores indicate better QOL]; mean DS domain score from the QLQ-MY20 was 24.1 at apheresis, 23.4 at lymphodepletion, and 33.7 at Month 2 [higher scores indicate more symptoms]; see Table 1). These decrements were followed by improvement back to baseline levels and, in some cases, improvement above baseline levels (eg, GHS was 67.9 and 65.0 at Months 4 and 5, respectively; DS was 18.3 and 17.8 at Months 4 and 5), though few patients had sufficient follow up to analyze QOL at later timepoints. Based on the PGIC, 77.8% of patients reported being “a little better” or “much better” as early as Month 1, though this number declined over time. Among non-CAR-T patients, QOL largely plateaued (GHS was 62.2 at baseline and 58.3 at Month 6), though disease symptoms improved over time (DS was 28.6 at baseline and 24.5 at Month 6; pain was 42.3 at baseline and 29.2 at Month 6). Based on the PGIC, 34.7% of patients reported being “a little better” or “much better” at Month 1, which improved to 50% by Month 6. CONCLUSIONS In this interim analysis of an ongoing prospective observational study, QOL and symptom measures generally worsened over the first few months for CAR-T patients in the real-world though improved to baseline levels and beyond at later time points. Patients did, however, directly report improvement in their disease state as early as Month 1 based on the PGIC. Non-CART patients generally showed a QOL plateau with some modest improvement in disease symptoms which was also reflected in their self-reported assessment of disease state improvement based on the PGIC.

Abstract Introduction/Objective Anaplastic thyroid carcinoma (ATC) is a fatal malignancy. We report an unusual case of a patient with ATC whose chief complaint and clinical history were listed as “jaundice and liver mass” without mention of disease in the neck. Methods/Case Report A 66-year-old female presented to the emergency department with worsening “yellow-green skin discoloration” for a few weeks. She also reported worsening dyspnea and recent dysphagia with solid foods, fatigue, abdominal pain and recent hemoptysis. Physical examination revealed conjunctival icterus, jaundice, a tender neck mass, right upper chest wall tenderness and palpable lymphadenopathy in the lower neck. Assessment notes indicated inability to carry out self-care and being bedridden, even though she reported having been active, swimming and cycling, up to one month before her presentation. Computed tomography studies confirmed findings compatible with widespread malignancy with mass lesions in her liver, lungs, adrenals, kidneys, neck, pancreas, gallbladder, and brain. Mild anemia, hemoglobin 10.5g/dL, mild leukocytosis, leukocytes 17,000/mm3, were confirmed. Bilirubin was 15µmol/L, and hepatic enzymes were elevated. An ultrasound-guided liver biopsy was performed and evaluated for cytologic features, histologic features and pattern of immunoreactivity. The combined cytomorphologic and histologic features were those of a pleomorphic sarcomatoid high-grade malignancy with variably spindled to epithelioid morphology and associated necrosis. Immunohistochemical studies performed on sections from the accompanying core biopsy confirmed the malignant cells to be positive with CK-AE1/AE3, CK 7, TTF-1, GATA3, PAX8, SATB2, and BRAF V600E. The malignant cells were nonreactive with CK 20, thyroglobulin, calcitonin, napsin, CDX2, PCEA, and ER. The combined clinical setting, imaging findings, cytomorphology, histomorphology and ancillary testing results together allowed for a specific diagnosis of metastatic anaplastic thyroid carcinoma. The patient was referred for palliative care services and died within a few days of diagnosis. Results (if a Case Study enter NA) NA Conclusion Metastatic disease from a sarcomatoid ATC, as diagnosed in this case, is an important differential diagnosis to keep in mind when an elderly patient presents with multisite metastases from an undefined primary source. Clinical, radiological and laboratory correlations are of paramount importance in correlating with cytomorphology/histomorphology and in helping to determine the best panel of IHC studies to consider.

Abstract Recurrence pattern in high grade glioma is classified as local and distant recurrence based on distance from original resection cavity and radiation field. We report the first series of three cases of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylated high grade glioma with distant recurrence without local recurrence throughout the disease course. Patient 1: 65 year-old female with WHO grade 4 glioblastoma, isocitrate dehydrogenase enzyme (IDH) wild type (WT), MGMT methylated. She underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was &lt; 1 ml. Distant recurrence occurred 4 months after completion of Stupp protocol. Patient 2: 55 year-old male with WHO grade 4 glioblastoma, IDH wild type, MGMT methylated. He underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was 18 ml. Distant recurrence occurred 5 months after completion of Stupp protocol. Patient 3: 31 year-old male with WHO grade 4 astrocytoma, IDH mutant, MGMT promoter methylated. He underwent gross total resection followed by Stupp protocol. Postoperative ischemic volume was 2 ml. Distant recurrence occurred 10 months after completion of Stupp protocol. Distant recurrence is more common in MGMT promoter methylated tumors. All 3 patients in our case series had poor outcomes after distant recurrence without local recurrence at the original tumor site. This observation indicates good local control in MGMT promoter methylated high grade glioma with current standard treatment. For one patient, next generation sequencing (NGS) was available for both original and recurrent tumor and did not reveal any major differences in the genetics of original tumor and distant recurrent tumor other than temozolomide induced high tumor mutational burden in the distant recurrent tumor. Understanding risk factors for distant recurrence in MGMT promoter methylated high grade gliomas and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve outcomes.

AbstractBackgroundThe PI3K/AKT pathway, extensively studied in cancer, is vital for regulating cell metabolism, differentiation, and proliferation. Pathogenic variants in the PIK3R1 gene, which encodes three regulatory units of class IA PI3Ks, have been found in affected tissue of individuals with vascular lesions. These variants predominantly occur in the iSH2 domain, disrupting inhibitory contacts with the catalytic unit and leading to PI3K activation. Germline variants in this gene are also linked to an immunological condition called Activated PI3K delta syndrome type 2 (APDS2).MethodsThis is a case report and literature review. Clinical data were retrieved from medical records.ResultsA male patient presented with extensive vascular malformation covering over 90% of his body, along with complete 2–3 toe syndactyly, suggesting a vascular malformation syndrome called PROS. Low levels of IgA and IgG were detected. The patient achieved his developmental milestones and had above‐average weight, height, and head circumference. Exome sequencing of skin and blood DNA revealed a de novo variant in PIK3R1 (c.1746‐2A>G, p.?) in 9% of the patient's blood cells and 25% of cultured fibroblasts. Initially, classified as a variant of uncertain significance, this variant was later confirmed to be the cause.ConclusionsThis is the first intronic SNV in a canonical splice site within iSH2 described, highlighting the importance of iSH2 in the regulation of the PI3K/AKT pathway and its involvement in the development of vascular overgrowth and antibody deficiency.