Post-expiry stability of freeze-dried plasma under field conditions - Can shelf life be extended?

BACKGROUND: This prospective study evaluated the effect of routine, uncontrolled, Israeli field storage conditions on the safety and efficacy of Lyo-Plas N Freeze-Dried Plasma (FDP) at the end of the manufacturer's shelf life, and up to 24 months post expiry. Clotting factors V, VIII and XI, proteins S, C, fibrinogen, PTT, ATIII, VWF, and INR as well as TEG, DDM, residual moisture, pH, and sterility of FDP returned from field units after uncontrolled storage were evaluated. STUDY DESIGN AND METHODS: Parameters measured at the end of manufacturer shelf life, as well as 6, 12, 18, and 24 months after expiry, were compared to those of freshly supplied FDP doses. RESULTS: Changes were found when comparing freshly supplied FDP to all field-stored groups in INR, PT, PTT, pH, fibrinogen, and factor VIII. A significant change was also seen in Factor XI in the 12, 18, and 24 months post-expiry samples, Factor V and R in the 24 months post-expiry samples, MA in the 12, 24 months post-expiry group, and Protein C in the 18 months post-expiry group. An increase in the residual moisture from 0.90% in freshly supplied FDP to 1.35% in 24 months post-expiry FDP.; all p < .05. No growth was found in sterility analysis. CONCLUSION: Despite uncontrolled field storage conditions, the findings demonstrate that the safety and efficacy of FDP units, stored in uncontrolled conditions are only slightly affected, even beyond their expiration date. This information allows consideration of possibly extending the shelf life.

Peripheral Nerve Block to Treat Pain Caused by Daboia palaestinae Envenomation.

Snakebite pain can be challenging to control. We describe our experience managing intolerable pain after conventional treatment failed. A 35-year-old man, presented after a viper snakebite, suffering from intolerable pain in the affected extremity. He had no significant past medical history. All attempts to control the pain conventionally were unsuccessful. Treatment with a supraclavicular nerve block resulted in immediate relief. After the block receded, only a dull pain remained, which later disappeared without recurrence. This experience illustrates the need for personalized pain treatment to avoid subsequent complications.

Can't intubate, can't oxygenate? What is the preferred surgical strategy? A retrospective analysis.

INTRODUCTION: Cricothyrotomy (CTM) is currently recommended as the preferred method due to its ease, speed, and safety in life-threatening airway emergencies where standard tracheal intubation and mask ventilation fail. MATERIAL AND METHODS: This retrospective study analyzed 33 cases of "can't intubate, can't oxygenate or ventilate" (CICOV): 12 of percutaneous dilatational tracheostomy (PDT) and 21 of CTM. The CTM group was younger (median age 44) and mainly consisted of trauma patients. The PDT group was more diverse and procedures were performed by anesthesia and critical care consultants. RESULTS: Initial success rates were 100% for PDT (12/12) and 86% for CTM (18/21), with one conversion from CTM to PDT. No perioperative complications occurred in the PDT group, while the CTM group experienced two cases of false tracts requiring re-do and three cases of bleeding. Immediate mortality within 24 hours was reported in 5/19 CTM patients and none in the PDT group. Successful liberation from mechanical ventilation at hospital discharge was achieved in 6/12 PDT patients and 11/21 CTM patients. Among the 21 CTM cases, all 16 survivors underwent subsequent tracheostomy. Tracheal decannulation occurred in 4/12 PDT patients and 10/21 CTM patients. Favorable immediate neurological outcomes (GCS ≥ 11T) were observed in 8/12 PDT patients and 8/21 CTM patients, while 3 PDT patients remained anesthetized until death and 7 CTM patients died within the first 72 hours without recovery attempts. CONCLUSIONS: In experienced hands, PDT could be a legitimate clinical option for the surgical airway in cases of CICOV. CTM may be more suitable for practitioners who encounter CICOV infrequently.

Using Artificial Intelligence to Predict Mechanical Ventilation Weaning Success in Patients with Respiratory Failure, Including Those with Acute Respiratory Distress Syndrome.

The management of mechanical ventilation (MV) remains a challenge in intensive care units (ICUs). The digitalization of healthcare and the implementation of artificial intelligence (AI) and machine learning (ML) has significantly influenced medical decision-making capabilities, potentially enhancing patient outcomes. Acute respiratory distress syndrome, an overwhelming inflammatory lung disease, is common in ICUs. Most patients require MV. Prolonged MV is associated with an increased length of stay, morbidity, and mortality. Shortening the MV duration has both clinical and economic benefits and emphasizes the need for better MV weaning management. AI and ML models can assist the physician in weaning patients from MV by providing predictive tools based on big data. Many ML models have been developed in recent years, dealing with this unmet need. Such models provide an important prediction regarding the success of the individual patient's MV weaning. Some AI models have shown a notable impact on clinical outcomes. However, there are challenges in integrating AI models into clinical practice due to the unfamiliar nature of AI for many physicians and the complexity of some AI models. Our review explores the evolution of weaning methods up to and including AI and ML as weaning aids.

ECG and Atrial Appendage Doppler Discordance Is Common in Patients Undergoing Cardiac Surgery: Prospective Study.

Background: Patients with atrial fibrillation (AF) remain at increased risk of thromboembolism despite apparent maintenance of sinus rhythm with the cause often attributed to periods of asymptomatic AF. Atrial mechanical discordance, with the body of the left atrium (LA) in sinus rhythm and the left atrial appendage (LAA) in AF may also be a contributor. Objectives: The purpose of this study was to assess the frequency of electrocardiogram (ECG) rhythm and LAA and/right atrial appendage (RAA) Doppler ejection phenotype (transesophageal echocardiography [TEE]) discordance in patients undergoing cardiac surgery. Methods: A total of 124 patients undergoing coronary artery bypass graft (CABG), CABG and valve surgery, or isolated valve repair or replacement (valve ± CABG) were prospectively studied. Intraoperative surface ECG rhythm strip and TEE were performed before cardiopulmonary bypass. The ECG and TEE LAA/RAA Doppler spectrum were independently classified as sinus or AF. Results: Of 107 patients (age 65 ± 12 years; 31% female; 65% CABG, 31% valve ± CABG) without a history of AF, 39 (36%) had ECG and LAA and/or RAA discordance (ECG/LAA Doppler discordance, n = 12 [11%]; ECG/RAA Doppler discordance, n = 35 [33%]). There was no significant difference between concordant and discordant groups with regard to age, gender, history of hypertension, diabetes, heart failure, or stroke (all P > 0.05). Conclusions: A large minority of patients without a history of AF undergoing cardiac surgery have ECG/atrial appendage Doppler discordance, a setting that may promote thromboembolism in non-anticoagulated patients. Clinical parameters do not identify patients at increased risk for discordance.

Prognosticating the outcome of intensive care in older patients-a narrative review.

Prognosis determines major decisions regarding treatment for critically ill patients. Statistical models have been developed to predict the probability of survival and other outcomes of intensive care. Although they were trained on the characteristics of large patient cohorts, they often do not represent very old patients (age ≥ 80 years) appropriately. Moreover, the heterogeneity within this particular group impairs the utility of statistical predictions for informing decision-making in very old individuals. In addition to these methodological problems, the diversity of cultural attitudes, available resources as well as variations of legal and professional norms limit the generalisability of prediction models, especially in patients with complex multi-morbidity and pre-existing functional impairments. Thus, current approaches to prognosticating outcomes in very old patients are imperfect and can generate substantial uncertainty about optimal trajectories of critical care in the individual. This article presents the state of the art and new approaches to predicting outcomes of intensive care for these patients. Special emphasis has been given to the integration of predictions into the decision-making for individual patients. This requires quantification of prognostic uncertainty and a careful alignment of decisions with the preferences of patients, who might prioritise functional outcomes over survival. Since the performance of outcome predictions for the individual patient may improve over time, time-limited trials in intensive care may be an appropriate way to increase the confidence in decisions about life-sustaining treatment.

When Palliative Care May Be the Only Option in the Management of Severe Burns: A Case Report Written With the Help of ChatGPT.

We present a case of 100% third-degree burns. The patient received full resuscitative measures, but the family was prepared for a poor outcome based on the severe extent of the injuries. After several days of treatment, it became apparent that the patient indeed could not survive the injuries and palliative care was instituted, including mechanical ventilation, fluid therapy, and analgesia. Surgery was not possible without causing major disfigurement, including enucleation of both eyes and amputation of all limbs.

Severity of a Vipera palaestinae envenomation objective findings associated with a complicated hospitalization course following a Vipera palaestinae bite.

The most common snake in Israel, responsible for most snakebites is Vipera palaestinae (VP). Envenomation signs and symptoms vary from local manifestations to systemic reactions that may end with death. Antivenom treatment, given to high-risk patients, reduces complications and mortality but carries risks. As of now, there is no standardized protocol for adults bitten by VP based on objective clinical and laboratory findings. We conducted A retrospective analysis of 159 patients admitted to two large tertiary care institutions in the center (Hadassah University Medical Center) and south (Soroka University Medical Center) of Israel with Vipera palaestinae bites during 1990-2017. Epidemiological and clinical data were extracted, and the patients were divided into two groups based on hospitalization time (over or under 48 h). 159 patients were included in this study. The average hospitalization time was 66.1 h, with 49.7% of patients admitted over 48 h. The main factors that statistically correlated with a longer hospitalization time were: Male gender, lower extremity bite, platelets lower than 150 K at presentation, leukocyte count of over 10 K at presentation and elevated D-Dimer levels. This study provides factors which are associated with a severe VP envenomation. These clinical or laboratory findings (along with accompanying clinical symptoms) are associated with a higher risk of a prolonged hospitalization with more complications and may require a more intensive treatment and monitoring.

Apoptotic cells for treatment of acute respiratory distress syndrome associated with COVID-19.

Background: Hyper-inflammatory immune response, a hallmark of severe COVID-19, is associated with increased mortality. Acute respiratory distress syndrome (ARDS) is a common manifestation. We undertook two phase I/II studies in five and then 16 subjects with severe/critical COVID-19 to assess the safety and preliminary efficacy of apoptotic cells (Allocetra™-OTS, Enlivex Therapeutics), a cellular immunomodulatory therapy that reprograms macrophages to reduce hyper-inflammatory response severity. Methods: Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra™-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra™-OTS. Results: 21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16/21 were males, 16/21 were overweight/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19/21 recovered completely. Comparable mortality rates at the hospital were 3.8%-8.9% for age- and gender-matched patients, and 39%-55% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines/chemokines. Conclusion: In patients with severe/critical COVID-19 associated with ARDS, Allocetra™-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation. Trial registration: https://clinicaltrials.gov/ct2/show/study/NCT04513470, https://clinicaltrials.gov/ct2/show/study/NCT04590053, Identifiers NCT04513470, NCT04590053.

The role of clinical phenotypes in decisions to limit life-sustaining treatment for very old patients in the ICU.

BACKGROUND: Limiting life-sustaining treatment (LST) in the intensive care unit (ICU) by withholding or withdrawing interventional therapies is considered appropriate if there is no expectation of beneficial outcome. Prognostication for very old patients is challenging due to the substantial biological and functional heterogeneity in that group. We have previously identified seven phenotypes in that cohort with distinct patterns of acute and geriatric characteristics. This study investigates the relationship between these phenotypes and decisions to limit LST in the ICU. METHODS: This study is a post hoc analysis of the prospective observational VIP2 study in patients aged 80 years or older admitted to ICUs in 22 countries. The VIP2 study documented demographic, acute and geriatric characteristics as well as organ support and decisions to limit LST in the ICU. Phenotypes were identified by clustering analysis of admission characteristics. Patients who were assigned to one of seven phenotypes (n = 1268) were analysed with regard to limitations of LST. RESULTS: The incidence of decisions to withhold or withdraw LST was 26.5% and 8.1%, respectively. The two phenotypes describing patients with prominent geriatric features and a phenotype representing the oldest old patients with low severity of the critical condition had the largest odds for withholding decisions. The discriminatory performance of logistic regression models in predicting limitations of LST after admission to the ICU was the best after combining phenotype, ventilatory support and country as independent variables. CONCLUSIONS: Clinical phenotypes on ICU admission predict limitations of LST in the context of cultural norms (country). These findings can guide further research into biases and preferences involved in the decision-making about LST. Trial registration Clinical Trials NCT03370692 registered on 12 December 2017.

Expert Evaluation of a Chicken Tissue-based Model for Teaching Ultrasound-guided Central Venous Catheter Insertion.

BACKGROUND: Ultrasound-guided central venous catheterization (CVC) is a commonly performed procedure which carries significant risks for complications. Current models used for simulation-based teaching are expensive and may not replicate tissue feel and ultrasound qualities of human tissues. We aimed to evaluate a tissue model composed of chicken breast and balloons and compare it to a commercially available mannequin. METHODS: Forty attending physicians from four departments with extensive CVC experience were enrolled. Participants completed an ultrasound-guided central line placement utilizing both models during a hands-on workshop. Following CVC placement on each model, participants completed a survey to assess their experience with that particular model. RESULTS: 40 attending physicians (12 (30%) anesthesia, 11 (28%) emergency medicine, 11 (28%) internal medicine, and 6 (15%) surgery) participated in the study. The chicken model was rated significantly higher than the mannequin model with regard to ultrasound quality (p=0.02) and tissue feel (p=0.002). In a direct comparison, participants rated the chicken model more highly than the mannequin in all categories except similarity to the human anatomy. Overall the chicken model was preferred to the mannequin, (mean score 44.5; standard deviation 26.0). The mannequin was rated higher with regard to similarity to human anatomy (mean score 52.8; standard deviation 25.7). The comparison between key features (ultrasound characteristics, similarity to human anatomy and teaching trainees) of the models did not vary significantly by area of practice, with the exception of ease of use (p=0.045). CONCLUSIONS: In this prospective study of experienced clinicians we found that a novel tissue model for ultrasound-guided CVC placement was rated more highly compared to a commercially available mannequin task trainer.

Multimodal Perioperative Ultrasound Course for Interns Allows for Enhanced Acquisition and Retention of Skills and Knowledge.

The ability to apply perioperative ultrasound techniques is a desirable skill for clinicians. We implemented a multimodal 13-day basic ultrasound course for 6 anesthesia interns. Their scores on a knowledge test increased after the course and were sustained and similar to those of 6 senior residents 90 days later. The interns acquired images of the heart in volunteers with little assistance after the course. They maintained their ability to acquire echocardiographic images on a simulator 90 days later with kinematic measures superior to the same seniors. Through this course, interns gained knowledge and skills equal to or greater than seniors.