Evaluating the Effect of a COVID-19 Predictive Model to Facilitate Discharge: A Randomized Controlled Trial

Background  We previously developed and validated a predictive model to help clinicians identify hospitalized adults with coronavirus disease 2019 (COVID-19) who may be ready for discharge given their low risk of adverse events. Whether this algorithm can prompt more timely discharge for stable patients in practice is unknown. Objectives  The aim of the study is to estimate the effect of displaying risk scores on length of stay (LOS). Methods  We integrated model output into the electronic health record (EHR) at four hospitals in one health system by displaying a green/orange/red score indicating low/moderate/high-risk in a patient list column and a larger COVID-19 summary report visible for each patient. Display of the score was pseudo-randomized 1:1 into intervention and control arms using a patient identifier passed to the model execution code. Intervention effect was assessed by comparing LOS between intervention and control groups. Adverse safety outcomes of death, hospice, and re-presentation were tested separately and as a composite indicator. We tracked adoption and sustained use through daily counts of score displays. Results  Enrolling 1,010 patients from May 15, 2020 to December 7, 2020, the trial found no detectable difference in LOS. The intervention had no impact on safety indicators of death, hospice or re-presentation after discharge. The scores were displayed consistently throughout the study period but the study lacks a causally linked process measure of provider actions based on the score. Secondary analysis revealed complex dynamics in LOS temporally, by primary symptom, and hospital location. Conclusion  An AI-based COVID-19 risk score displayed passively to clinicians during routine care of hospitalized adults with COVID-19 was safe but had no detectable impact on LOS. Health technology challenges such as insufficient adoption, nonuniform use, and provider trust compounded with temporal factors of the COVID-19 pandemic may have contributed to the null result. Trial registration  ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT04570488","term_id":"NCT04570488"}}NCT04570488.     

Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin lymphomas: frequency,genetic mechanisms,and clinical significance

Programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are immunomodulatory molecules over-expressed in lymphomas and are promising immunotherapy targets for hematologic malignancies. However, studies of PD-1/PD-L1 overexpression and their clinical significance in aggressive pediatric non-Hodgkin lymphomas (NHL) are limited. We assessed PD-1/PD-L1 overexpression using immunohistochemistry in 68 aggressive pediatric NHL: ALK-positive anaplastic large cell lymphoma (ALK+ ALCL, n=8), Burkitt lymphoma (BL, n=27), and large B-cell lymphoma (LBCL) de novo LBCL, n=22 and diffuse LBCL arising as monomorphic post-transplant lymphoproliferative disorder [PTLD-DLBCL], n=11. In LBCL, correlations between PD-L1 overexpression and Epstein-Barr virus (EBV) status, cell of origin, stage, nodal status, overall survival (OS), and event-free survival (EFS) were examined. The genetic mechanisms of PD-L1 overexpression were investigated using targeted next-generation sequencing (NGS) and cytogenetic data. All ALK+ ALCL samples, 50.0% of de novo LBCL (11/22), 72.7% of PTLD-DLBCL (8/11), and no BL overexpressed PD-L1. Overexpressed PD-L1 correlated with EBV positivity (P=0.033) in LBCL and lower EFS in de novo LBCL (P=0.017). NGS of select LBCL revealed distinct somatic mutations and an ultra-hypermutated PTLD-DLBCL. Most cases with 9p24.1 copy gains overexpressed PD-L1 although some cases had no discernible genetic drivers of PD-L1 overexpression. Overexpressed PD-L1 is common in pediatric LBCL, associated with EBV positivity and 9p24.1 gains, and may have prognostic significance in de novo LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in aggressive pediatric NHL can occur. Thus, additional studies exploring the therapeutic and prognostic significance and molecular mechanisms of PD-L1 overexpression in aggressive pediatric NHL are warranted.     

Reexcision and perioperative brachytherapy in the treatment of local relapse after breast conservation: a possible alternative to mastectomy

Breast conserving surgery and postoperative radiotherapy became widely accepted in the last two decades for the treatment of early invasive breast cancer. In spite of adequate surgery and radiotherapy, the rate of ipsilateral breast tumor recurrence is approximately 10%. In such cases salvage mastectomy is the standard treatment, however wide reexcision of the recurrent tumor is also a reasonable option for selected patients. The risk of second local relapse is higher following further breast conservation compared to mastectomy. The authors report the technique of tumor reexcision combined with intraoperative implantation and perioperative high dose rate (HDR) bracytherapy of the tumor bed for the salvage of recurrence in a previously irradiated breast. One can perform two operative interventions at the same time with this method. Irradiation can be started safely within 48 hours after surgery. A review of the literature is also performed by the authors to demonstrate the role and indication of perioperative brachytherapy in the treatment of breast tumor relapse and other cancer recurrences. Reexcision is a practicable alternative to mastectomy for solitary, parenchymal breast tumor relapse measured 2 cm or less in diameter. Perioperative brachytherapy may decrease the risk of second relapse without increasing radiation side effects. Further prospective study is required to define the value of the prescribed method in comparison with salvage mastectomy.     

Predictors and outcomes of jejunostomy tube placement at the time of pancreatoduodenectomy

BackgroundClinically relevant postoperative pancreatic fistula and delayed gastric emptying cause substantial morbidity after pancreatoduodenectomy. Per international guidelines, the placement of jejunostomy tubes may be considered for patients at risk for malnutrition, such as those with a high risk for clinically relevant postoperative pancreatic fistula and related complications. This study determined predictors and postoperative outcomes of jejunostomy tube placement.MethodsPatients undergoing pancreatoduodenectomy in 2014 to 2015 were identified using the American College of Surgeons National Surgical Quality Improvement Program and Procedure-Targeted Pancreatectomy Participant Use Files. Multivariable logistic regressions were used to identify factors associated with concurrent jejunostomy tube placement and postoperative outcomes.ResultsOf 3,600 patients, 8.9% underwent jejunostomy tube placement. Patients given a jejunostomy tube were more likely white (odds ratio 1.46, P = .016), to have low preoperative serum albumin levels (odds ratio 2.13, P < .001), to have received neoadjuvant radiotherapy (odds ratio 2.14, P < .001), and to have received an intraoperative transfusion (odds ratio 1.50, P = .004). We observed no association between jejunostomy tube placement and an increasing number of risk factors for clinically relevant postoperative pancreatic fistula (P = .96) or delayed gastric emptying (P = .54). Overall, jejunostomy tube placement was associated with increased morbidity (odds ratio 1.34, P = .020) and duration of stay (P < .001), but not mortality (P = .12). Among patients with low serum albumin or those who developed clinically relevant postoperative pancreatic fistula or delayed gastric emptying, jejunostomy tube utilization was not associated with morbidity or mortality.ConclusionJejunostomy tube placement during pancreatoduodenectomy was not driven by risk factors for clinically relevant postoperative pancreatic fistula or delayed gastric emptying, suggesting that practice patterns play a role. Among patients with at-risk preoperative albumin or who developed these complications, jejunostomy tube placement was not associated with worse outcomes, supporting selective utilization per guideline recommendations.     

Detection of mono- and di-hexoses as metabolites of 4-bromoaniline using HPLC-TOF-MS/MS

1. The metabolic fate of 4-bromoaniline (4-BrA) was investigated in rat following intraperitoneal administration at 50?mg kg ? 1 using HPLC-TOF-MS/MS. 2. The sensitivity provided by the use of TOF-MS/MS, aided by the distinctive isotope pattern resulting from the presence of the bromine substituent in the molecule, enabled the detection of many previously uncharacterized metabolites in the samples. 3. Several groups of minor metabolites were detected in the urine that corresponded to a number of isomeric hexose and di-hexose-containing conjugates (possibly glucosides and diglucosides) of 4-BrA. 4. As well as hexose and di-hexose conjugates of 4-BrA, several further groups of metabolites that also contained either a sulphamate or sulphate group in addition to the sugar moieties were also detected.     

Effects of dehydroepiandrosterone and flutamide on hippocampal CA1 spine synapse density in male and female rats: implications for the role of androgens in maintenance of hippocampal structure

The effects of androgens and the androgen antagonist, flutamide, on the density of dendritic spine synapses in the CA1 subfield of the hippocampus were studied in gonadectomized male and female rats. Treatment of orchidectomized male rats with dehydroepiandrosterone (DHEA; 2 d, 1 mg/d sc) increased the density of CA1 spine synapses observed 2 d later, by 106%, without significantly affecting ventral prostate weight. The hippocampal response to DHEA was unaffected by blockade of intracerebral estrogen biosynthesis using the aromatase inhibitor, letrozole. By contrast, flutamide alone (2 d; 5 mg/d, sc) increased CA1 spine synapse density by 66%, whereas in combination the effects of flutamide and DHEA were additive rather than inhibitory. Additive effects on CA1 synapse density were also observed in males using combinations of flutamide with 5alpha-dihydrotestosterone (2 d, 500 microg/d, sc). At the same doses, flutamide had no effect on prostate weight and completely blocked the effects on the prostate of treatment with 5alpha-dihydrotestosterone. Treatment of ovariectomized females with DHEA increased CA1 spine synapse density to a level similar to that observed in the male. As in males, flutamide in females increased CA1 spine synapse formation and further augmented the response to DHEA. These results demonstrate that flutamide and DHEA have positive effects on hippocampal CA1 spine synapse density in both sexes. They also suggest that conventional measures of androgen agonist or antagonist activity, exemplified by ventral prostate growth, may not be indicative of effects on hippocampal CA1 synaptogenesis.