Citations

AbstractBackgroundIn the management of Gram‐negative bloodstream infection (GN‐BSI), short antimicrobial courses have been increasingly demonstrated to be non‐inferior to prolonged therapy, with lower risk of Clostridioides difficile infection (CDI) and emergence of multi‐drug resistant (MDR) organisms. However, immunocompromised hosts were excluded from these studies. We investigated outcomes of short (≤10 days), intermediate (11–14 days), and prolonged (≥15 days) antimicrobial durations for GN‐BSI in neutropenic patients.MethodsA retrospective cohort study was conducted on neutropenic patients with monomicrobial GN‐BSI between 2018 and 2022. The primary outcome was a composite of all‐cause mortality and microbiologic relapse within 90 days after therapy completion. The secondary outcome was a composite of 90‐day CDI and development of MDR‐GN bacteria. Cox regression analysis with propensity score (PS) adjustment was used to compare outcomes between the three groups.ResultsA total of 206 patients were classified into short (n = 67), intermediate (n = 81), or prolonged (n = 58) duration. Neutropenia was predominantly secondary to hematopoietic stem cell transplantation (48%) or hematologic malignancy (35%). The primary sources of infection included intra‐abdominal (51%), vascular catheter (27%), and urinary (8%). Most patients received definitive therapy with cefepime or carbapenem. No significant difference in the primary composite endpoint was observed for intermediate versus short (PS‐adjusted hazard ratio [aHR] 0.89; 95% confidence interval [95% CI] 0.39–2.03) or prolonged versus short therapy (PS‐aHR 1.20; 95% CI 0.52–2.74). There was no significant difference in the secondary composite endpoint of CDI or MDR‐GN emergence.ConclusionOur data suggest that short antimicrobial courses had comparable 90‐day outcomes as intermediate and prolonged regimens for GN‐BSI among immunocompromised patients with neutropenia. image

3083 Background: Cancer-Specific Plectin (CSP) is a novel pro-tumorigenic target that is selectively expressed on the surface of tumors, while absent from benign tissue. CSP is highly expressed in many solid cancers, particularly pancreatic (PC), cholangiocarcinoma (CCA), and ovarian (OC). ZB131 (Zielbio), is a humanized anti-CSP IgG1 monoclonal antibody that binds specifically to CSP on the surface of tumor cells, rapidly internalizes and modulates key proliferative and cytoskeletal remodeling signaling pathways to decrease cancer cell growth and increase the recruitment of anti-tumor immune infiltrates. Methods: The dose escalation (3+3 design) and expansion are enrolling adult patients (pts) with advanced treatment-refractory solid tumors. ZB131 was administered IV over 60 minutes (without premedication) weekly. The starting dose of ZB131 is 0.3 mg/kg followed by 1,3, 9, 15 and 30 mg/kg. Primary objectives are safety, tolerability, and maximum tolerated dose/determination of Phase 2 dose. Secondary objectives are preliminary efficacy (RECIST v1.1), Pharmacokinetic (PK) and pharmacodynamic parameters in blood and paired tumor biopsies. Results: As of 31 Jan 2023, 24 pts had enrolled (9 PC, 6 CCA, 4 OC, 5 other). The median age was 59.5 yr (range, 35 – 84) with a median of 4 prior lines of therapy. The median ZB131 treatment duration is 5.3 weeks (range, 1 – 33). No dose-limiting toxicities were observed up to the dose of 30 mg/kg which is currently enrolling. Treatment-related adverse events (TRAEs) were grade 1/ 2: nausea (n=6), fatigue (n=5), anemia (n=3), diarrhea (n=2), flulike symptoms (n=2), and vomiting (n=2). Mild flu-like symptoms and nausea/vomiting were observed during or following infusion at doses of 9 mg/kg and above. Except for one episode of Gr 3 neutropenia at the 30 mg/kg dose, no other drug-related grade 3/4 TRAE’s were reported. Five pts had stable disease range, 12 – 33 weeks (2 PC, 1 CCA, 2 OC), with a 43% decrease in CA-125 observed in one OC pt. The PKs are linear and dose-proportional for all dose levels evaluated (estimated T ½ of 6-9 days). No antidrug antibodies have been detected. Conclusions: Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472 .

AbstractBackgroundIt is challenging to assess the accuracy of volume CT Dose Index (CTDIvol) when the axial scan modes corresponding to a helical scan protocol are not available. An alternative approach was proposed to directly measure using helical acquisitions and relatively small differences (< 20%) from CTDIvol were observed.PurposeTo visually demonstrate the 3D dose distribution for both axial and helical CT acquisitions and quantitively compare and CTDIvol.Methods3D dose distribution within the standard CTDI phantoms (16 and 32 cm diameter) from a single CT projection, Dp(x,y,z) was first generated using Monte Carlo simulation (GEANT4) with 9×108 photons per combination of tube voltage (80–140 kV), collimation width (1–8 cm), and z‐axis location of the central ray of the x‐ray beam, with a spatial resolution of 1 mm3. These dose distributions from one single projection were analytically ensembled to simulate 3D dose volumes DA(x,y,z) and DH(x,y,z) for axial and helical scans, respectively, with different helical pitches (0.3–2) and scan lengths (100–150 mm). 2D planar dose distributions were obtained by integrating the inside 100 mm of the dose volumes. CTDIvol and were calculated using the planar dose data at corresponding pencil chamber locations and the percentage differences (PD) were reported.ResultsHigh spatial resolution 3D CT dose volumes were generated and visualized. PDs between and CTDIvol had strong dependency on scan length and peripheral chamber locations, with subtle dependency on collimation width and pitch. PDs were mostly within the range of ± 3% for a scan length of 150 mm with four peripheral chamber locations.ConclusionsWith a scan length covering the entire phantom length, directly measured from helical scans can serve as an alternative to CTDIvol only if all four peripheral locations were measured.

Gastrointestinal (GI) cancers, including esophageal, gastroesophageal junction, gastric, duodenal and distal small bowel, biliary tract, pancreatic, colon, rectal, and anal cancer, comprise a heterogeneous group of malignancies that impose a significant global burden. Immunotherapy has transformed the treatment landscape for several GI cancers, offering some patients durable responses and prolonged survival. Specifically, immune checkpoint inhibitors (ICIs) directed against programmed cell death protein 1 (PD-1), either as monotherapies or in combination regimens, have gained tissue site-specific regulatory approvals for the treatment of metastatic disease and in the resectable setting. Indications for ICIs in GI cancer, however, have differing biomarker and histology requirements depending on the anatomic site of origin. Furthermore, ICIs are associated with unique toxicity profiles compared with other systemic treatments that have long been the mainstay for GI cancer, such as chemotherapy. With the goal of improving patient care by providing guidance to the oncology community, the Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of GI cancer. Drawing from published data and clinical experience, the expert panel developed evidence- and consensus-based recommendations for healthcare professionals using ICIs to treat GI cancers, with topics including biomarker testing, therapy selection, and patient education and quality of life considerations, among others.

Abstract Objective To assess the relationship between ovarian hyperstimulation syndrome (OHSS) and adverse outcomes using population-based data in the United States. The hypothesis is that patients with OHSS were more likely to deliver preterm and more likely to have hypertensive disorders. Methods This retrospective cohort study identified 94 patients with OHSS and 183 matched referents in eight counties in Minnesota. Data were collected regarding pregnancy history, infertility treatment, and pregnancy outcomes. Using the Rochester Epidemiology Project, study subjects were identified from female patients, aged 18 to 49 years, who were diagnosed with infertility from January 2, 1995 to December 1, 2017, and had a pregnancy greater than 20 weeks' gestation. The primary outcome was preterm delivery or hypertensive disorder of pregnancy incidence in the OHSS group when compared with control patients. Chi-squared test, t test, and multivariate logistic models were used where appropriate. Results Patients with OHSS were more likely to deliver preterm (odds ratio, 2.14; 95% confidence interval, 1.26–3.65; P < 0.01), and their neonates were more likely to be small for gestational age (odds ratio, 4.78; 95% confidence interval, 1.61–14.19; P < 0.01). No significant differences between the groups were observed in any other outcome. Patients with OHSS are more likely to deliver preterm if they undergo fresh transfer compared with a freeze all and subsequent frozen transfer (odds ratio, 3.03, 95% confidence interval, 1.20–7.66, P = 0.02). Conclusion OHSS may lead to preterm birth and small-for-gestational-age neonates, which changes patient counseling and leads to arranging specialized obstetrical care for these patients with OHSS.

ABSTRACT A 65-year-old man presented with hematuria, night sweats, nausea, intermittent nonbloody diarrhea, and abdominal pain. Computed tomography angiogram with enterography showed retroperitoneal fibrosis surrounding both kidneys and ureters without any evidence of vascular obstruction or hydronephrosis. Laparoscopic biopsy demonstrated fibroadipose tissue involved by a subtle histiocytic infiltrate in a background of marked fibrosis, scattered lymphocytes, and plasma cells. The histiocytes strongly expressed CD163, Factor XIIIa, and BRAF V600E . He was diagnosed with Erdheim-Chester disease, a rare histiocytic neoplasm uncommonly presenting with gastroenterological manifestations.

LBA2 Background: Radiation with sensitizing fluoropyrimidine (5FUCRT) is a standard curative intent treatment for LARC. It improves disease-free survival (DFS) by decreasing pelvic recurrence but has short- and long-term toxicity. The PROSPECT trial compares FOLFOX chemotherapy with selective use of 5FUCRT (intervention) to 5FUCRT (control) for neoadjuvant treatment prior to TME for LARC. Methods: Eligible patients (pts) had cT2N+, cT3N-, cT3N+ rectal cancers deemed appropriate for neoadjuvant therapy prior to low anterior resection with TME. Pts with distal, T4 tumors, threatened radial margins or > 4 enlarged lymph nodes were ineligible. Pts were randomized 1:1 without blinding. Pts in the control group received 5FUCRT with 5040 cGy over 5.5 weeks with either capecitabine or 5FU. Pts in the intervention group had 6 cycles of mFOLFOX6 followed by restaging. If tumor regression was > 20%, then TME was performed without radiation; if < 20%, 5FUCRT was given before TME. DFS was the 1°outcome, defined as time from randomization to any recurrence or death, analyzed in the per-protocol population. One interim analysis was conducted with α spending = 0.001. Noninferiority (NI) of the intervention could be claimed if the upper limit of the 2-sided 90.2% confidence interval (CI) of the DFS hazard ratio did not exceed 1.29 (NI margin). Secondary endpoints included overall survival (OS), local recurrence free survival, R0 resection, pathologic complete response (CR), and toxicity. Results: From June 2012 to December 2018, 1194, pts were randomized and 1128 initiated protocol-assigned treatment. Median age was 57, 34.5% were women and 61.9% had clinically positive nodes. 53 of 585 pts in the intervention group (9%) received preop 5FUCRT. DFS was analyzed after 227 events and median follow-up of 58 months. Conclusions: FOLFOX chemotherapy with selective use of 5FUCRT is non-inferior to 5FUCRT for neoadjuvant treatment of LARC prior to low anterior resection with TME. Patients and physicians have alternative strategies for management of LARC. Clinical trial information: NCT01515787 . [Table: see text]

A virtual medical visit, also known as telemedicine or telehealth, is a valuable alternative method of providing health care to patients who do not have easy access to a hospital, or during times when limited social interaction is crucial such as our current COVID-19 pandemic. A virtual approach to evaluating musculoskeletal system ailments is particularly challenging, for diagnosis of these conditions generally rely greatly on physical examination, which may be challenging. However, a properly planned and executed telemedicine visit will yield successful results in most cases. Our aim is to produce a document with instructions and suggestions, including physical examination maneuvers, to help physicians carry out a proper virtual medical visit with patients complaining of ankle musculoskeletal problems. Virtual visits should not be thought of as a replacement for traditional face-to-face medical consultations, but rather a complementary method to provide health care when deemed appropriate. By following this guide, and tailoring it to the specific case at hand, medical providers should be able to effectively carry out a successful telemedicine consultation for musculoskeletal ailments relating to the ankle. Levels of Evidence: Level V