Improvement in inpatient discharge planning for patients with alcohol use disorder with the implementation of a team-based multidisciplinary workflow.

BACKGROUND: Alcohol use disorder (AUD) is a major economic and healthcare burden in the United States. While there is evidence-based medication-assisted treatment (MAT) for AUD, few physicians implement these therapies on a regular basis. OBJECTIVE: To determine the impact of a pharmacy-guided AUD discharge planning workflow on the rate of MAT prescriptions and inpatient readmissions. METHODS: This was a single-centered pre-and-post intervention study over a 6-month period, with a 90-day pre-intervention period and a 90-day post-intervention period. The study included all patients over the age of 18 years admitted to a medicine or surgery floor bed who presented with alcohol withdrawal at any point during their hospital course. The intervention involved a pharmacy workflow, in which a list of patients admitted with alcohol withdrawal was automatically generated and referred to pharmacists, who then provided recommendations to the primary physician regarding prescriptions for naltrexone, acamprosate, and/or gabapentin. The patients were then contacted within 30 days after discharge for post-hospitalization follow-up. Our outcome measures were change in prescription rate of MATs, change in total and alcohol-related 90-day readmission rates, and change in total and alcohol-related 90-day emergency department (ED) visit rates. RESULTS: The pre-intervention period consisted of 49 patients and the post-intervention period consisted of 41 patients. Our workflow demonstrated a 195% increase in the prescription rate of MATs at discharge (p < 0.001), 61% reduction in 90-day total readmission rate (p < 0.05), 40% reduction in 90-day total ED visit rate (p = 0.09), 92% reduction in 90-day alcohol-related readmission rate (p < 0.05), and 88% reduction in 90-day alcohol-related ED visit rate (p < 0.05). CONCLUSIONS: Our intervention demonstrated that a pharmacy-based AUD discharge planning workflow has the potential to reduce inpatient readmissions and ED visits for patients with AUD, thus demonstrating improved patient outcomes with the potential to reduce healthcare costs.

A Case of Non-cirrhotic Hyperammonemic Encephalopathy in a Patient With Metastatic Gastrointestinal Stromal Tumor.

Acute toxic encephalopathy (ATE) is a widely recognized medical emergency with an expansive differential. One particular known etiology for ATE is elevated ammonia, a powerful neurotoxin that often presents with clinical findings of confusion, disorientation, tremors, and in severe cases, coma and death. Hyperammonemia is most commonly associated with liver disease and presents as hepatic encephalopathy in the setting of decompensated cirrhosis; however, in rare cases, a patient may suffer from non-cirrhotic hyperammonemic encephalopathy. We describe the case of a 61-year-old male with metastatic gastrointestinal stromal tumor who was diagnosed with non-cirrhotic hyperammonemic encephalopathy, and briefly explore the literature describing its mechanisms.

Analysis of Post-Transplant Lymphoproliferative Disorder (PTLD) Outcomes with Epstein-Barr Virus (EBV) Assessments-A Single Tertiary Referral Center Experience and Review of Literature.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations ranging from polyclonal reactive proliferations to overt lymphomas that develop as consequence of immunosuppression in recipients of solid organ transplantation (SOT) or allogeneic bone marrow/hematopoietic stem cell transplantation. Immunosuppression and Epstein-Barr virus (EBV) infection are known risk factors for PTLD. Patients with documented histopathologic diagnosis of primary PTLD at our institution between January 2000 and October 2019 were studied. Sixty-six patients with PTLD following SOT were followed for a median of 9.0 years. The overall median time from transplant to PTLD diagnosis was 5.5 years, with infant transplants showing the longest time to diagnosis at 12.0 years, compared to pediatric and adolescent transplants at 4.0 years and adult transplants at 4.5 years. The median overall survival (OS) was 19.0 years. In the monomorphic diffuse large B-cell (M-DLBCL-PTLD) subtype, median OS was 10.7 years, while median OS for polymorphic subtype was not yet reached. There was no significant difference in OS in patients with M-DLBCL-PTLD stratified by quantitative EBV viral load over and under 100,000 copies/mL at time of diagnosis, although there was a trend towards worse prognosis in those with higher copies.

A novel vitamin D gene therapy for acute myeloid leukemia.

Current treatment approaches for older adult patients with acute myeloid leukemia (AML) are often toxic and lack efficacy. Active vitamin D3 (1,25(OH)2D3) has been shown to induce myeloid blast differentiation but at concentrations that have resulted in unacceptable, off-target hypercalcemia in clinical trials. In our study, we found that the combination of 1,25(OH)2D3 and the hypomethylating agent (HMA) 5-Azacytidine (AZA) enhanced cytotoxicity and differentiation, and inhibited proliferation of several AML cell lines (MOLM-14, HL60) and primary AML patient samples. This observation was corroborated by our RNA sequence analysis data in which VDR, CD14, and BAX expression were increased, and FLT-3, PIM1 and Bcl-2 expression were decreased. To address the hypercalcemia issue, we genetically engineered MOLM-14 cells to constantly express CYP27B1 (the VD3 activating enzyme, 1-α-hydroxylase-25(OH)D3) through lentiviral transduction procedures. Subsequently, we used these cells as vehicles to deliver the CYP27B1 enzyme to the bone marrow of AML mice. We observed that AML mice with CYP27B1 treatment had longer overall survival compared to no treatment and displayed no significant change in calcium level.

Primary chemoradiation with cisplatin versus cetuximab for locally advanced head and neck cancer: a retrospective cohort study.

OBJECTIVE: To explore the efficacy of primary chemoradiation with cisplatin versus cetuximab with respect to HPV/p16 and smoking statuses. METHODS: We retrospectively reviewed patients from our center with locally advanced non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) who received primary chemoradiation with cisplatin or cetuximab between 2006 and 2018. RESULTS: The median OS for cisplatin (n = 66) was not reached versus 132 months when treated with cetuximab (n = 55) (p = 0.03). For HPV/p16-positive patients, we found the median OS for cisplatin (n = 34) was not reached versus 60 months with cetuximab (n = 21) (p = 0.036). In the smoking group, the median OS was not reached in the cisplatin group (n = 44) versus 60 months when treated with cetuximab (n = 32) (p = 0.03). CONCLUSION: HPV/p16-positive and smoking cohorts treated with cisplatin-based chemoradiotherapy had a significantly better OS versus cetuximab.

Combination Chemohormonal Therapy in Metastatic Salivary Duct Carcinoma.

BACKGROUND Salivary duct carcinoma (SDC) is a rare, aggressive head and neck cancer with frequent metastases. Current treatment options for recurrent or metastatic SDC include targeted anti-androgen therapy, HER2-targeted therapy, or systemic chemotherapy. We report the first use of a combination chemohormonal strategy. CASE REPORT A 68-year-old male who had never smoked with a past medical history of two-vessel coronary artery disease and systolic heart failure presented with a parotid mass and underwent surgical resection. Biopsy of the mass revealed high-grade, androgen receptor-positive and Erb-B2 receptor tyrosine kinase-2 (ERBB2)-amplified positive SDC. He subsequently received adjuvant radiation therapy. Four months after completion of adjuvant radiation therapy, recurrence with symptomatic pleural effusion and nodes, hepatic metastases, and boney metastases occurred. Due to significant symptomatic tumor, a rapid treatment response was desired. Combination chemohormonal therapy (CHT) was initiated with carboplatin area under the curve 4 and paclitaxel, 200 mg/m² in 21-day cycles along with combined androgen blockade using leuprolide, 45 mg subcutaneously every 6 months and bicalutamide, 50 mg daily. The treatment was well tolerated with fatigue as the main adverse event. Positron emission tomography-computed tomography at 3 and 6 months after treatment initiation showed good partial response. The patient experienced uveal progression after 8 months and alternate treatment was started. CONCLUSIONS Combination CHT with carboplatin, paclitaxel, and combined androgen deprivation may be a good treatment option in androgen receptor-positive recurrent or metastatic SDC if rapid treatment response is desired. Combination chemotherapy with androgen deprivation for validation through clinical trials.

Reversible Polymorphic Transition and Hysteresis-Driven Phase Selectivity in Single-Crystalline C8-BTBT Rods.

Organic semiconductors (OSCs) are highly susceptible to the formation of metastable polymorphs that are often transformed by external stimuli. However, thermally reversible transformations in OSCs with stability have not been achieved due to weak van der Waals forces, and poor phase homogeneity and crystallinity. Here, a polymorph of a single crystalline 2,7-dioctyl[1] benzothieno[3,2-b][1]benzothio-phene rod on a low molecular weight poly(methyl methacrylate) (≈120k) that limits crystal coarsening during solvent vapor annealing is fabricated. Molecules in the polymorph lie down slightly toward the substrate compared to the equilibrium state, inducing an order of greater resistivity. During thermal cycling, the polymorph exhibits a reversible change in resistivity by 5.5 orders with hysteresis; this transition is stable toward bias and thermal cycling. Remarkably, varying cycling temperatures leads to diverse resistivities near room temperature, important for nonvolatile multivalue memories. These trends persist in the carrier mobility and on/off ratio of the polymorph field-effect transistor. A combination of in situ grazing incident wide angle X-ray scattering analyses, visualization for electronic and structural analysis simulations, and density functional theory calculations reveals that molecular tilt governs the charge transport characteristics; the polymorph transforms as molecules tilt, and thereby, only a homogeneous single-crystalline phase appears at each temperature.

Humanin (HN) and glucose transporter 8 (GLUT8) in pregnancies complicated by intrauterine growth restriction.

BACKGROUND: Intrauterine growth restriction (IUGR) results from a lack of nutrients transferred to the developing fetus, particularly oxygen and glucose. Increased expression of the cytoprotective mitochondrial peptide, humanin (HN), and the glucose transporter 8, GLUT8, has been reported under conditions of hypoxic stress. However, the presence and cellular localization of HN and GLUT8 in IUGR-related placental pathology remain unexplored. Thus, we undertook this study to investigate placental expression of HN and GLUT8 in IUGR-affected versus normal pregnancies. RESULTS: We found 1) increased HN expression in human IUGR-affected pregnancies on the maternal aspect of the placenta (extravillous trophoblastic (EVT) cytoplasm) compared to control (i.e. appropriate for gestational age) pregnancies, and a concomitant increase in GLUT8 expression in the same compartment, 2) HN and GLUT8 showed a protein-protein interaction by co-immunoprecipitation, 3) elevated HN and GLUT8 levels in vitro under simulated hypoxia in human EVT cells, HTR8/SVneo, and 4) increased HN expression but attenuated GLUT8 expression in vitro under serum deprivation in HTR8/SVneo cells. CONCLUSIONS: There was elevated HN expression with cytoplasmic localization to EVTs on the maternal aspect of the human placenta affected by IUGR, also associated with increased GLUT8 expression. We found that while hypoxia increased both HN and GLUT8, serum deprivation increased HN expression alone. Also, a protein-protein interaction between HN and GLUT8 suggests that their interaction may fulfill a biologic role that requires interdependency. Future investigations delineating molecular interactions between these proteins are required to fully uncover their role in IUGR-affected pregnancies.

Origin of the emergence of higher T c than bulk in iron chalcogenide thin films.

Fabrication of epitaxial FeSexTe1-x thin films using pulsed laser deposition (PLD) enables improving their superconducting transition temperature (T c) by more than ~40% than their bulk T c. Intriguingly, T c enhancement in FeSexTe1-x thin films has been observed on various substrates and with different Se content, x. To date, various mechanisms for T c enhancement have been reported, but they remain controversial in universally explaining the T c improvement in the FeSexTe1-x films. In this report, we demonstrate that the controversies over the mechanism of T c enhancement are due to the abnormal changes in the chalcogen ratio (Se:Te) during the film growth and that the previously reported T c enhancement in FeSe0.5Te0.5 thin films is caused by a remarkable increase of Se content. Although our FeSexTe1-x thin films were fabricated via PLD using a Fe0.94Se0.45Te0.55 target, the precisely measured composition indicates a Se-rich FeSexTe1-x (0.6 < x < 0.8) as ascertained through accurate compositional analysis by both wavelength dispersive spectroscopy (WDS) and Rutherford backscattering spectrometry (RBS). We suggest that the origin of the abnormal composition change is the difference in the thermodynamic properties of ternary FeSexTe1-x, based on first principle calculations.