Patient-specific Predictors of Haemolysis with Percutaneous Ventricular Assist Devices.

Introduction: Percutaneous ventricular assist devices (pVADs) are increasingly used in cardiogenic shock but are associated with complications including haemolysis. The aim of this study was to investigate patient characteristics associated with haemolysis in cardiogenic shock patient population.

Methods: Consecutive patients were identified using Current Procedural Terminology (CPT) codes for pVAD insertion.

The potential radiosensitization target PFKFB3 is related to response to radiotherapy in SweBCG91RT: a randomized clinical trial with long-term follow-up.

Background: Several cancer types have increased PFKFB3, a glycolytic enzyme for which potent inhibitors have been found. Inhibition of PFKFB3 impairs DNA repair after irradiation of cancer cells, making it a possible radiosensitization target. The SweBCG91RT trial, in which breast cancer patients were randomized to postoperative radiotherapy or not, was used to investigate PFKFB3 as a clinical marker of sensitivity to adjuvant radiotherapy.

Tertiary lymphoid structures in high-grade serous tubo-ovarian carcinoma: anatomical site matters.

Tertiary lymphoid structures (TLS) in the tumor microenvironment are prognostically beneficial in many solid cancer types. Reports on TLS in high-grade serous tubo-ovarian carcinoma (HGSC) are few, and the prognostic impact is unclear. We investigated mature TLS (mTLS), immature TLS (iTLS) and lymphoid aggregates (LA) in primary adnexal tumors (PTs) and synchronous omental/peritoneal metastases (pMets) of HGSC.

Evaluation of Insulin Dosing Strategies for Hyperkalemia Management at an Academic Medical Center.

Purpose: While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia.

Methods: Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified.

Guide to Lung-Protective Ventilation in Cardiac Patients.

The incidence of acute respiratory insufficiency has continued to increase among patients admitted to modern-day cardiovascular intensive care units. Positive pressure ventilation (PPV) remains the mainstay of treatment for these patients. Alterations in intrathoracic pressure during PPV has distinct effects on both the right and left ventricles, affecting cardiovascular performance.

Evaluation of Goal Phenytoin Levels After an Initial Intravenous Loading Dose at an Academic Medical Center.

Background: Phenytoin intravenous loading doses are administered in status epilepticus to rapidly achieve therapeutic levels. Accurately assessing phenytoin levels after the initial load can be challenging because of its complex pharmacokinetic profile and nonstandardized weight-based loading doses.

Objectives: The objectives of this analysis were to determine the incidence of patients achieving goal phenytoin levels after the initial loading dose and characterize factors that contribute to achieving the goal level.

Combining histological grade, TILs, and the PD-1/PD-L1 pathway to identify immunogenic tumors and de-escalate radiotherapy in early breast cancer: a secondary analysis of a randomized clinical trial.

Background: The implementation of immunological biomarkers for radiotherapy (RT) individualization in breast cancer requires consideration of tumor-intrinsic factors. This study aimed to investigate whether the integration of histological grade, tumor-infiltrating lymphocytes (TILs), programmed cell death protein-1 (PD-1), and programmed death ligand-1 (PD-L1) can identify tumors with aggressive characteristics that can be downgraded regarding the need for RT.

Methods: The SweBCG91RT trial included 1178 patients with stage I-IIA breast cancer, randomized to breast-conserving surgery with or without adjuvant RT, and followed for a median time of 15.

Modifiable Mechanical Ventilation Targets Are Associated With Improved Survival in Ventilated VA-ECLS Patients.

Background: In acute respiratory distress syndrome (ARDS), lung protective ventilation (LPV) improves patient outcomes by minimizing ventilator-induced lung injury. The value of LPV in ventilated patients with cardiogenic shock (CS) requiring venoarterial extracorporeal life support (VA-ECLS) is not known, but the extracorporeal circuit provides a unique opportunity to modify ventilatory parameters to improve outcomes.

Objectives: The authors hypothesized that CS patients on VA-ECLS who require mechanical ventilation (MV) may benefit from low intrapulmonary pressure ventilation (LPPV), which has the same end goals as LPV.

Low levels of WRAP53 predict decreased efficacy of radiotherapy and are prognostic for local recurrence and death from breast cancer: a long-term follow-up of the SweBCG91RT randomized trial.

Downregulation of the DNA repair protein WD40-encoding RNA antisense to p53 (WRAP53) has been associated with radiotherapy resistance and reduced cancer survival. The aim of this study was to evaluate WRAP53 protein and RNA levels as prognostic and predictive markers in the SweBCG91RT trial, in which breast cancer patients were randomized for postoperative radiotherapy. Using tissue microarray and microarray-based gene expression, 965 and 759 tumors were assessed for WRAP53 protein and RNA levels, respectively.

Proteogenomics decodes the evolution of human ipsilateral breast cancer.

Ipsilateral breast tumor recurrence (IBTR) is a clinically important event, where an isolated in-breast recurrence is a potentially curable event but associated with an increased risk of distant metastasis and breast cancer death. It remains unclear if IBTRs are associated with molecular changes that can be explored as a resource for precision medicine strategies. Here, we employed proteogenomics to analyze a cohort of 27 primary breast cancers and their matched IBTRs to define proteogenomic determinants of molecular tumor evolution.

Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Outcomes in Left Ventricular Assist Device Patients with Aortic Insufficiency.

Worsening aortic insufficiency (AI) is a known sequela of prolonged continuous-flow left ventricular assist device (LVAD) support with a significant impact on patient outcomes. While medical treatment may relieve symptoms, it is unlikely to halt progression. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are among non-medical interventions available to address post-LVAD AI.

Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients.

Background: Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC.

Objective: The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients.

Co-occurrence of Myocardial Sarcoidosis and Left Ventricular Non-compaction in a Patient with Advanced Heart Failure.

A 46-year-old man with systolic heart failure, end-stage renal disease on dialysis, ventricular tachycardia and pulmonary sarcoidosis presented with decompensated heart failure and cardiogenic shock of unknown aetiology. The hospital course was complicated by worsening shock requiring inotropic and mechanical circulatory support, as well as eventual dual heart and kidney transplantation. Cardiac imaging was used to assess the aetiology of the patient's non-ischaemic cardiomyopathy, including a PET scan and cardiac MRI.

Efficacy of anti-PD-1 and ipilimumab alone or in combination in acral melanoma.

Background: Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population.

Stability of alteplase for ultrasound-facilitated catheter-directed thrombolysis.

Ultrasound-facilitated catheter-directed thrombolysis is used with low-dose alteplase to treat pulmonary embolism. This reduces the risk of bleeding that accompanies systemic administration of higher alteplase doses. Some studies suggest that alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of alteplase under these conditions.

PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature.

Introduction: Programmed death-ligand 1 (PD-L1) expression is used for treatment prediction in non-small cell lung cancer (NSCLC). While cytology may be the only available material in the routine clinical setting, testing in clinical trials has mainly been based on biopsies.

Methods: We included 2 retrospective cohorts of paired, concurrently sampled, cytological specimens and biopsies.

MET Expression and Cancer Stem Cell Networks Impact Outcome in High-Grade Serous Ovarian Cancer.

Overexpression of the receptor tyrosine kinase MET has been linked to poor survival in several cancer types, and MET has been suggested to interact with stem cell networks. In vitro studies have further suggested a possible benefit of a combined treatment using PARP and MET inhibitors. We used a tissue microarray (TMA) with 130 samples of advanced-stage high-grade serous fallopian tube/ovarian cancer (HGSC) to investigate the prognostic value of MET protein expression alone and in combination with the stem cell factor SOX2.

Proteogenomic Workflow Reveals Molecular Phenotypes Related to Breast Cancer Mammographic Appearance.

Proteogenomic approaches have enabled the generat̲ion of novel information levels when compared to single omics studies although burdened by extensive experimental efforts. Here, we improved a data-independent acquisition mass spectrometry proteogenomic workflow to reveal distinct molecular features related to mammographic appearances in breast cancer. Our results reveal splicing processes detectable at the protein level and highlight quantitation and pathway complementarity between RNA and protein data.

Intravenous levothyroxine stewardship program at a tertiary academic medical center.

Purpose: Based on the pharmacokinetic profile of levothyroxine, a 3-day hold guideline for adult patients ordered for intravenous (IV) levothyroxine was implemented at a tertiary academic medical center. The purpose of this study was to evaluate the impact of the implementation of an IV levothyroxine hold guideline.

Methods: This single-center, retrospective analysis identified patients ordered for IV levothyroxine during a 13-week period before and after implementation of the guideline.

Evaluation of Desmopressin in Critically Ill Patients with Hyponatremia Requiring 3% Hypertonic Saline.

Background: Desmopressin (DDAVP) is often used for hyponatremia management but has been associated with increases in hospital length of stay and duration of hypertonic saline use. The purpose of this study was to evaluate hyponatremia management strategies and their effect on sodium correction in critically ill patients requiring 3% hypertonic saline (3HS).

Methods: This retrospective, single-center study included critically ill patients with hyponatremia (serum sodium ≤ 125 mEq/L) receiving 3HS from May 31 2015, to May 31 2019.

Safety of Intravenous Push Lacosamide Compared With Intravenous Piggyback at a Tertiary Academic Medical Center.

Background: There are limited data regarding the incidence of adverse events associated with administering lacosamide by intravenous push (IVP) compared with IV piggyback (IVPB).

Objective: The objective of this analysis was to compare the safety profile, including cardiovascular effects, sedative effects, and IV site reactions of IVP and IVPB lacosamide administration.

Methods: A retrospective pre/post cohort analysis comparing patients who received lacosamide via IVP and IVPB was conducted.

Evaluation of Cost, Workflow, and Safety of Implementing a Vial Transfer Device for Ready-to-Mix Drugs at an Academic Medical Center.

Objective: To evaluate the cost, workflow, and safety of implementing a vial transfer device system.

Methods: In this retrospective analysis, pharmacy systems and electronic health record reports identified high-volume and high-cost medications prepared by a Vial2Bag (V2B) system from July 2017 to June 2018. The major outcome was the extrapolated yearly cost avoidance (EYCA) from utilization of a V2B system, calculated by subtracting total costs of the V2B system from total cost of ready-to-use products and locally compounded sterile products.