When to Stop Antibiotics in the Critically Ill?

Over the past century, antibiotic usage has skyrocketed in the treatment of critically ill patients. There have been increasing calls to establish guidelines for appropriate treatment and durations of antibiosis. Antibiotic treatment, even when appropriately tailored to the patient and infection, is not without cost.

The scientific rationale and study protocol for the DPP3, Angiotensin II, and Renin Kinetics in Sepsis (DARK-Sepsis) randomized controlled trial: serum biomarkers to predict response to angiotensin II versus standard-of-care vasopressor therapy in the treatment of septic shock.

Background: Data to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin-angiotensin-aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock.

Investigation of the Methodology of Specific Airway Resistance Measurements in COPD.

Introduction: Specific resistance (SR) measurements in Chronic Obstructive Pulmonary Disease (COPD) patients may be performed by panting or tidal breathing. The aim of this study was to compare how breathing frequency affected SR in COPD and compare different tangent plotting methods.

Methods: Fifteen COPD patients participated.

Exhaled nitric oxide, eosinophils and current smoking in COPD patients.

https://bit.ly/3PSWvM2.

Absence of BTK, BCL2, and PLCG2 Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax.

Purpose: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study.

Patients And Methods: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12-13 cycles of ibrutinib plus venetoclax).

Ibrutinib combination therapy for advanced gastrointestinal and genitourinary tumours: results from a phase 1b/2 study.

Background: Ibrutinib, a first-in-class inhibitor of Bruton's tyrosine kinase, is approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. Based on encouraging preclinical data, safety and efficacy of ibrutinib combined with companion drugs for advanced renal cell carcinoma (RCC), gastric/gastroesophageal junctional adenocarcinoma (GC), and colorectal adenocarcinoma (CRC) were evaluated.

Methods: Ibrutinib 560 mg or 840 mg once daily was administered with standard doses of everolimus for RCC, docetaxel for GC, and cetuximab for CRC.

Takotsubo Cardiomyopathy Syndrome in Critical Care Transport: A Case and Critical Review.

Takotsubo cardiomyopathy syndrome, or simply takotsubo syndrome (TTS), is a form of stress cardiomyopathy thought to be caused by excess catecholamines in association with physical or emotional stress. Providers should maintain a high index of suspicion for TTS in patients with symptoms of acute coronary syndrome, acute decompensated heart failure, substernal chest pain, or dyspnea. However, TTS is a diagnosis of exclusion, and patients should initially be evaluated and treated for other causes, such as acute myocardial infarction.

Pediatric Chest Compression Improvement Via Augmented Reality Cardiopulmonary Resuscitation Feedback in Community General Emergency Departments: A Mixed-Methods Simulation-Based Pilot Study.

Background: Yearly, more than 20,000 children experience a cardiac arrest. High-quality pediatric cardiopulmonary resuscitation (CPR) is generally challenging for community hospital teams, where pediatric cardiac arrest is infrequent. Current feedback systems are insufficient.

B-cell Receptor Pathway Mutations Are Infrequent in Patients with Chronic Lymphocytic Leukemia on Continuous Ibrutinib Therapy.

Purpose: Acquired mutations in Bruton's tyrosine kinase (BTK) or phospholipase C-γ2 (PLCG2) genes are associated with clinical progressive disease (PD) in patients with chronic lymphocytic leukemia (CLL) treated with BTK inhibitors. Data on mutation rates in patients without PD on ibrutinib treatment are limited.

Experimental Design: We evaluated frequency and time to detection of BTK and PLCG2 mutations in peripheral blood samples from 388 patients with previously untreated (n = 238) or relapsed/refractory (n = 150) CLL across five clinical trials.

Results from a Phase 1b/2 Study of Ibrutinib Combination Therapy in Advanced Urothelial Carcinoma.

Ibrutinib is a first-in-class Bruton's tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies and chronic graft-versus-host disease. We evaluated the safety and efficacy of ibrutinib, alone or combined with standard-of-care regimens, in adults with advanced urothelial carcinoma (UC). Once-daily ibrutinib was administered orally at 840 mg (single-agent or with paclitaxel) or at 560 mg (with pembrolizumab).

Outcomes of coronavirus disease 2019 (COVID-19) and risk factors associated with severe COVID-19 in patients with mature B-cell non-Hodgkin lymphomas: A US electronic health record cohort study.

Objectives: The objectives of this study were to assess the risk of severe coronavirus disease 2019 (COVID-19) outcomes in patients with mature B-cell non-Hodgkin lymphoma (mature B-cell NHL) compared with other cancers and to identify risk factors associated with severe COVID-19.

Methods: This study used Optum's electronic health record database. Risk factors were evaluated using multivariable logistic regression.

Paediatric chest compression performance improves via novel augmented-reality cardiopulmonary resuscitation feedback system: A mixed-methods pilot study in a simulation-based setting.

Aim: More than 20,000 children experience a cardiac arrest event each year in the United States. Most children do not survive. High-quality cardiopulmonary resuscitation (CPR) has been associated with improved outcomes yet adherence to guidelines is poor.

Expiratory flow limitation in a cohort of highly symptomatic COPD patients.

The Question Addressed By The Study: Small airway collapse during expiration, known as expiratory flow limitation (EFL), can be detected using oscillometry and is associated with worse clinical outcomes in COPD. This study investigated the prevalence of EFL in a cohort of highly symptomatic patients, evaluated clinical and lung function characteristics of patients with EFL and studied the repeatability of EFL over 6 months.

Materials/patients And Methods: 70 patients were recruited.

First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab chlorambucil plus obinutuzumab: final analysis of the randomized, phase III iLLUMINATE trial.

iLLUMINATE is a randomized, open-label phase III study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or <65 years with coexisting conditions. Patients received oral ibrutinib 420 mg once daily until disease progression or unacceptable toxicity or six cycles of oral chlorambucil, each in combination with six cycles of intravenous obinutuzumab.

Methacholine challenges: comparison of different tidal breathing challenge methods.

Tidal-breathing methacholine challenges are now recommended by guidelines, to avoid the bronchoprotective effects of deep inhalation. This study compared different tidal breathing methacholine challenge methods; assessed the agreement between tidal dosimetric and continuous output challenges; and assessed challenge repeatability with different methods. 15 asthma patients performed dosimetric challenges and a continuous-output breath-actuated challenge, all ≥3 days apart.

CuZrO: If it exists it should be a sandwich.

CuZrO has been hypothesized to be a catalytic material with potential applications for CO reduction. Unfortunately, this material has received limited attention in the literature, and to the best of our knowledge the exact crystal structure is still unknown. To address this challenge, we utilize several different structural prediction techniques in concert, including the Universal Structure Predictor: Evolutionary Xtallography (USPEX), the Materials Project Structure Predictor, and the Open Quantum Materials Database (OQMD).

Ibrutinib Plus Venetoclax for First-Line Treatment of Chronic Lymphocytic Leukemia: Primary Analysis Results From the Minimal Residual Disease Cohort of the Randomized Phase II CAPTIVATE Study.

Purpose: CAPTIVATE (NCT02910583), a randomized phase II study, evaluates minimal residual disease (MRD)-guided treatment discontinuation following completion of first-line ibrutinib plus venetoclax treatment in patients with chronic lymphocytic leukemia (CLL).

Methods: Previously untreated CLL patients age < 70 years received three cycles of ibrutinib and then 12 cycles of combined ibrutinib plus venetoclax. Patients in the MRD cohort who met the stringent random assignment criteria for confirmed undetectable MRD (Confirmed uMRD) were randomly assigned 1:1 to double-blind placebo or ibrutinib; patients without Confirmed uMRD (uMRD Not Confirmed) were randomly assigned 1:1 to open-label ibrutinib or ibrutinib plus venetoclax.

Impact of long-term ibrutinib treatment on circulating immune cells in previously untreated chronic lymphocytic leukemia.

This study evaluated long-term immunophenotypic changes in circulating levels of 24 immune cell subsets through 4 years of continuous treatment with first-line ibrutinib (420 mg once daily) in 31 patients with chronic lymphocytic leukemia (CLL) from the RESONATE-2 study, and compared them with untreated age-matched healthy donors (n = 20). Ibrutinib progressively decreased total B-cell counts and preferentially targeted malignant CLL B cells over normal B cells. Elevated counts of chronically activated, exhausted, and effector memory T cells were normalized within 6-16 months, while naive T cells remained mostly within healthy donor range (HDR).

Prediction of Outcome in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib: Development and Validation of a Four-Factor Prognostic Model.

Purpose: Randomized trials established the superiority of ibrutinib-based therapy over chemoimmunotherapy in chronic lymphocytic leukemia. Durability of progression-free survival (PFS) with ibrutinib can vary by patient subgroup. Clinical tools for prognostication and risk-stratification are needed.