Continuous infusion

BACKGROUND: To perform a systematic review with meta-analysis with the dual intent of assessing the impact of attaining aggressive vs. conservative beta-lactams PK/PD target on the clinical efficacy for treating Gram-negative infections in critical patients, and of identifying predictive factors of failure in attaining aggressive PK/PD targets. METHODS: Two authors independently searched PubMed-MEDLINE and Scopus database from inception to 23rd December 2023, to retrieve studies comparing the impact of attaining aggressive vs...

Background: Acute Respiratory Distress syndrome (ARDS) is a clinical syndrome of noncardiac pulmonary edema and inflammation leading to acute respiratory failure. We used the oleic acid infusion pig model of ARDS resembling human disease to explore cytokine changes in white blood cells (WBC) and plasma proteins, comparing baseline to ARDS values. Methods: Nineteen juvenile female swine were included in the study. ARDS defined by a PaO2 /FiO2 ratio < 300 was induced by continuous oleic acid infusion. Arterial blood was drawn before and during oleic acid infusion, and when ARDS was established...

Antiplatelet therapy is mandatory for prevention of thrombotic events in patients with a recent history of acute coronary syndromes and/or percutaneous coronary interventions. However, if an urgent surgery is required during antiplatelet therapy, a compromise between the ischemic/thrombotic and hemorrhagic risk has to be reached. Different bridging schemes are reported in the literature, but there is no clear consensus on the optimal treatment strategy in terms of efficacy and safety. Although some indications about the perioperative management of antiplatelet therapy regarding specific surgical specializations are available, balancing the thrombotic and hemorrhagic risk on an individual basis, no evidence referring to neurosurgical or neuro-oncologic procedures is reported...

Acute intermittent porphyria (AIP) is a rare autosomal dominant metabolic disorder with low penetrance, often presenting with a broad spectrum of clinical manifestations. Acute neurovisceral attacks commonly occur in young women, mimicking signs and symptoms of other medical and psychiatric conditions, thus delaying the diagnosis. We present the case of an 18-year-old female college student with recurrent hospitalizations for intractable abdominal pain, now again with pain and new subjective hematuria. The patient had previously undergone an endoscopy/colonoscopy with negative biopsies and serologies for acute pathology, including celiac disease...

BACKGROUND: Pain, including associated pain management, remains a burden on patients after thoracic surgery. Our objective was to investigate whether perioperative intravenous administration of lidocaine reduces postoperative morphine consumption and pain intensity after video-assisted thoracoscopic surgery (VATS). METHODS: In this double-blind, placebo-controlled superiority trial, patients undergoing VATS with a planned duration of ≤90 minutes were randomized within an intention-to-treat setting...

BACKGROUND: Pulmonary embolism (PE) is the leading cause of in-hospital death and the third most frequent cause of cardiovascular death. The clinical presentation of PE is variable, and choosing the appropriate treatment for individual patients can be challenging. CASE SUMMARY: A 64-year-old man presented to hospital with acute chest pain, shortness of breath, and pulmonary oedema. Electrocardiogram revealed ST-elevation myocardial infarction. D-dimer was 18.8 mg/L fibrinogen equivalent units (FEU) (normal <0...

In this systematic review, we assessed the safety and possible safety events of native glucose-dependent insulinotropic polypeptide (GIP)(1-42) in human studies with administration of synthetic human GIP. We searched the PubMed database for all trials investigating synthetic human GIP(1-42) administration. A total of 67 studies were included. Study duration ranged from 30minutes to 6 days. In addition to healthy individuals, the studies included individuals with impaired glucose tolerance, type 2 diabetes, type 1 diabetes, chronic pancreatitis and secondary diabetes, latent autoimmune diabetes in adults, diabetes caused by a mutation in the hepatocyte nuclear factor 1-alpha gene, end-stage renal disease, chronic renal insufficiency, critical illness, hypoparathyroidism, or cystic fibrosis-related diabetes...

Device aided therapies (DAT) comprising the intrajejunal administration of levodopa/carbidopa intestinal gel (LCIG) and levodopa/carbidopa/entacapone intestinal gel (LECIG), the continuous subcutaneous application of foslevodopa/foscarbidopa or apomorphine infusion (CSAI) and deep brain stimulation (DBS) are used to treat Parkinson's disease with insufficient symptom alleviation under intensified pharmacotherapy. These DAT significantly differ in their efficacy profiles, indication, invasiveness, contraindications, and potential side effects...

Methemoglobinemia is a potentially life-threatening, rare condition in which the oxygen-carrying capacity of hemoglobin is diminished. We present the case of a 3-year-old boy treated for T-cell acute lymphoblastic leukemia (T-ALL) who developed methemoglobinemia (MetHb 57.1%) as a side effect of ifosfamide administration. Due to his critical condition, the patient was transferred to the intensive care unit (ICU). The therapy included methylene blue administration, an exchange transfusion, catecholamine infusion, and steroids...

The nociceptive withdrawal reflex (NWR) is a physiological, polysynaptic spinal reflex occurring in response to noxious stimulations. Continuous NWR threshold (NWRt) tracking has been shown to be possibly useful in the depth of anesthesia assessment. The primary aim of this study was to describe how propofol modulates the NWRt over time in pigs. Five juvenile pigs (anesthetized three times) were included. An intravenous (IV) infusion of propofol (20 mg/kg/h) was started, and boli were administered to effect until intubation...

Background/Objectives: Intravenous dexmedetomidine (DEX) can increase the analgesia duration of peripheral nerve block; however, its effect in combination with superior trunk block (STB) remains unclear. We examined whether combining single-shot STB (SSTB) with intravenous DEX would provide noninferior postoperative analgesia comparable to that provided by continuous STB (CSTB). Methods: Ninety-two patients scheduled for elective arthroscopic rotator cuff repair were enrolled in this prospective randomized trial...

PURPOSE: Maintaining hemodynamic stability during cardiac ablation under general anesthesia is challenging. Remimazolam, a novel ultrashort-acting benzodiazepine, is characterized by maintaining comparatively stable blood pressure and does not influence the cardiac conduction system, which renders it a reasonable choice for general anesthesia for cardiac ablation. We aimed to evaluate whether remimazolam is associated with a decreased incidence of intraoperative hypotension compared with desflurane...

Lutetium-177 prostate-specific membrane antigen (177 Lu-PSMA)-targeted radiopharmaceutical therapy is a clinically approved treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Even though common practice reluctantly follows "one size fits all" approach, medical community believes there is significant room for deeper understanding and personalization of radiopharmaceutical therapies. To pursue this aim, we present a 3-dimensional spatiotemporal radiopharmaceutical delivery model based on clinical imaging data to simulate pharmacokinetic of 177 Lu-PSMA within the prostate tumors...

The 2023 Viral Clearance Symposium (VCS) was hosted by Takeda on 24 and 25 May 2023 in Vienna, Austria. The present conference extended the structure of the previous biennial symposia held between 2009 and 2019. As recapitulated in the introductory session, the genesis of the VCS, as described in the Proceedings of the 2009 VCS was "the worldwide regulatory and industry recognition that challenges, gaps, and opportunities exist, that it formally addressed could benefit the field as whole." This report provides a synopsis of the progress achieved at the conference resulting from detailed technical discussions and the pending questions that still require attention to address...

Session 7 of the 2023 Viral Clearance Symposium reviewed progresses in virus retentive filtrations applied to both upstream and downstream processing. Upstream topics included investigations and applications of media viral filtration for upstream cell culture viral risk mitigation. Downstream topics included evaluation of viral breakthrough in continuous processing using surrogate particles and demonstration of extensive viral filtration cycling with flow interruptions and long duration in connected process...

At the time of the 2023 Viral Clearance Symposium in Vienna, the ongoing revision of ICH Guideline Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin clearly was the dominant regulatory topic. At the symposium, the changes expected for Q5A(R2) to mirror advances of scientific knowledge, for example, the inclusion of new products, including viral-vector-derived ones, that can be subject to virus clearance, deliberations around continuous manufacturing processes, the use of prior knowledge to supplement or in part replace virus validation studies, and new molecular methods for detection of adventitious viruses, were discussed by a European and a US regulator as well as representatives from industry associations that had been involved with the drafting process...

The continuous processing session at the 2023 Viral Clearance Symposium (VCS) focused on understanding how to effectively design viral clearance operations for use in continuous processes and methods to perform viral clearance studies. In this session, an approach to directly address control considerations with operating continuous-flow reactors for low pH viral inactivation was presented. Continuous-flow low pH incubation chamber design and implications for residence time determination were discussed. Additionally, viral clearance capability between batch operation and connected operation were demonstrated to be comparable for a connected bind-elute chromatography and flow-through chromatography step...

Session 5 of the 2023 Viral Clearance Symposium reviewed the strategy and process understanding of viral clearance testing. Topics included learnings from the past, leveraging surrogate-based methodologies, cleaning agents that inactivate enveloped baculoviruses, segregation, and retrovirus-like particles both in continuous process and in-use as spiking viruses. Overall, there were discussions over a wide array of viral clearance determinants.

BACKGROUND: Remimazolam is a novel, ultrashort-acting benzodiazepine. This study aimed to compare the efficacy and safety of remimazolam and propofol for hysteroscopic examination, to determine the optimal dose of remimazolam combined with alfentanil for painless hysteroscopy, and to calculate its median effective dose (ED50). METHODS: Step 1: A total of 208 patients undergoing hysteroscopic examination were prospectively included in this study. Patients were randomized into 4 groups: 0...

Despite world-class sophisticated technologies, robotics, artificial intelligence, and machine learning approaches, cancer-associated mortalities and morbidities have shown continuous increments posing a healthcare burden. Drug-based interventions were associated with systemic toxicities and several limitations. Natural bioactive compounds derived nanoformulations, especially nanoquercetin (nQ), are alternative options to overcome drug-associated limitations. Moreover, the EVs-based cargo targeted delivery of nQ can have enormous potential in treating hepatocellular carcinoma (HCC)...