Care Med Research Articles

A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure

A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure

Nangibotide for precision immunomodulation in septic shock and COVID-19

Nangibotide for precision immunomodulation in septic shock and COVID-19

Extracellular vesicles: A promising therapy against SARS-CoV-2 infection

Extracellular vesicles: A promising therapy against SARS-CoV-2 infection

A Case of Acute Intravascular Hemolysis During Dialysis: A Quiz

A Case of Acute Intravascular Hemolysis During Dialysis: A Quiz

Three Zone Scanning Protocol For Lung Ultrasound: An Anatomical Basis.

Lung ultrasound is rapidly gaining popularity based on point of care ease of use, diagnostic fidelity and lack of ionizing radiation. This was particularly notable at the beginning of the COVID-19 pandemic, where concerns of contamination of the x-ray department led to a reluctance to order frequent chest x-rays. Early COVID-19 lung involvement is of a bronchopneumonia, and patches of consolidation adjacent to the chest wall were easily detectable by ultrasound. A large number of proposed scanning protocols were advocated and are often complex and largely based on traditional stethoscope examination or access points on the chest wall rather than the underlying lung anatomy. A surgical understanding of lung anatomy and related surface anatomy has led us to develop a simplified three zone scanning protocol in 2013. The anterior zone corresponds to the upper lobe, and the posterior zone is divided between upper lobe and lower lobe. The relationship between lung lobes and the surface of the chest wall provides the anatomical basis for a simple three scanning zone lung ultrasound protocol.

“TEG” talks: technology worth spreading?

“TEG” talks: technology worth spreading?

Long COVID outcomes in an asthmatic cohort and its implications for asthma control

Long COVID outcomes in an asthmatic cohort and its implications for asthma control

Fluorinated triphenylphosphonium analogs improve cell selectivity and invivo detection of mito-metformin.

Triphenylphosphonium (TPP+) conjugated compounds selectively target cancercells by exploiting their hyperpolarized mitochondrial membrane potential. Todate, studies have focused on modifying either the linker or the cargo of TPP+-conjugated compounds. Here, we investigated the biological effects ofdirect modification to TPP+ to improve the efficacy and detection of mito-metformin (MMe), a TPP+-conjugated probe we have shown to have promising preclinical efficacy against solid cancer cells. We designed, synthesized, and tested trifluoromethyl and methoxy MMe analogs (pCF3-MMe, mCF3-MMe, and pMeO-MMe) against multiple distinct human cancer cells. pCF3-MMe showed enhanced selectivity toward cancer cells compared to MMe, while retaining thesame signaling mechanism. Importantly, pCF3-MMe allowed quantitative monitoring of cellular accumulation via 19F-NMR invitro and invivo. Furthermore, adding trifluoromethyl groups to TPP+ reduced toxicity invivo while retaining anti-tumor efficacy, opening an avenue to de-risk these next-generation TPP+-conjugated compounds.

Inhibition of the LRRC8A channel promotes microglia/macrophage phagocytosis and improves outcomes after intracerebral hemorrhagic stroke.

Promoting microglial/macrophage (M/Mφ) phagocytosis accelerates hematoma clearance and improves the prognosis of intracerebral hemorrhagic stroke (ICH). Cation channels such as Piezo1 modulate bacterial clearance by regulating M/Mφ. Whether LRRC8A, an anion channel, affects M/Mφ erythrophagocytosis and functional recovery after ICH was investigated here. We found that LRRC8A is highly expressed on M/Mφ in the perihematomal region of ICH mice. Conditional knockout of Lrrc8a in M/Mφ or treatment with an LRRC8A channel blocker accelerated hematoma clearance, reduced neuronal death, and improved functional recovery after ICH. Mechanistically, the LRRC8A channel inhibition promoted M/Mφ phagocytosis by activating AMP-activated protein kinase (AMPK), thereby inducing nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and increasing Cd36 transcription. Our findings illuminate the regulation of M/Mφ phagocytosis by the LRRC8A channel via the AMPK-Nrf2-CD36 pathway after ICH, suggesting that LRRC8A is a potential target for hematoma clearance in ICH treatment.

Collapsed Woman With a D-Shaped Left Ventricle on Echocardiogram

A 45-year-old woman presented to the emergency department with unwitnessed out-of-hospital cardiac arrest with asystole rhythm. After intubation, transesophageal echocardiography was performed to search for possible etiologies of cardiac arrest. It showed a D-shaped left ventricle at the midventricular level in the transgastric short-axis view (Figure A and Video, available at http://www.annemergmed.com). After the return of spontaneous circulation, transesophageal echocardiography revealed the resolution of the D-shaped left ventricle (Figure B). Dilated right ventricle because of cardiac arrest. The right ventricle to left ventricle ratio was described as an echocardiographic sign suggesting pulmonary embolism with high specificity in previous studies.1Fields J.M. Davis J. Girson L. et al.Transthoracic echocardiography for diagnosing pulmonary embolism: a systematic review and meta-analysis.J Am Soc Echocardiogr. 2017; 30: 714-723.e4Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar In our case, right ventricle dilation with septal flattening was also observed during resuscitation, which returned to normal size after the return of spontaneous circulation. In Aagaard's porcine studies,2Aagaard R. Caap P. Hansson N.C. et al.Detection of pulmonary embolism during cardiac arrest—ultrasonographic findings should be interpreted with caution.Crit Care Med. 2017; 45: e695-e702Crossref PubMed Scopus (27) Google Scholar,3Aagaard R. Granfeldt A. Bøtker M.T. et al.The right ventricle is dilated during resuscitation from cardiac arrest caused by hypovolemia: a porcine ultrasound study.Crit Care Med. 2017; 45: e963-e970Crossref PubMed Scopus (32) Google Scholar the right ventricle size showed no correlation with the causes of arrest. The right ventricle dilation might be inherent to cardiac arrest. Our case supported Aagaard’s studies; therefore, the dilated right ventricle noted on the echocardiography during resuscitation must be interpreted cautiously. Other differential diagnoses should be considered if the dilated right ventricle resolves after the return of spontaneous circulation. In patients with cardiac arrest, thrombus visualized in the proximal pulmonary arteries or right heart might be a more specific sign to diagnose pulmonary embolism and guide further treatment, such as thrombolytic therapy.4Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1340) Google Scholar Gastric ulcer perforation was diagnosed following the return of spontaneous circulation by computed tomography. Gastrorrhaphy and drainage of intra-abdominal abscess were done; however, the patient died the next day because of a profound septic shock. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiI0ODMwZGY4ZmNmZjg3MWZkNjRiYzVkNTgyMjQ1YTNhNyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjcwOTg5Mzc1fQ.GE5j2RbdtAaHLdnx_AuVeAXfSftnIEpj1OAn9NZU9Stpu06w5LMVtZlgBhaB1tMFs6TOjMwr5LfsP17MhOD7AgBQr4O2BAy1vl0OVBHuhL5TuNK8RFAIVShVmQL_BYFiB4Py1xh8kiU5JsL9kuInpRDAEX4P1ANaxTL9CyTD4X3O9sFEHJLh6LgERT2fq6XjhXu3qODqLCmCDR5S7EOiP8HuU5Mt_PONO5bLGStTYYHOK1vIP7OlT_nLlacBrdeUxJqIHmLdtMZCEkZLFAPedhLGI0Tok-ncrbC-qlUnk1JI2PIYwPtgdKEJrxh6SHIK4D0haEmqAqE7Fbj6EggPDw Download .mp4 (2.92 MB) Help with .mp4 files VideoThe transesophageal echocardiography showing a D-shaped left ventricle at the midventricular level in the transgastric short-axis view during resuscitation, which turned back to a normal shape after the return of spontaneous circulation was achieved.

Risk of pre-existing hyponatremia and mortality in patients with traumatic brain injury across age groups

Traumatic brain injurySodiumClinical outcomes.

Olfactory dysfunction in COVID-19: pathology and long-term implications for brain health.

Decreased smell function is related to brain health, future mortality, and quality of life. Most people inflicted with the SARS-CoV-2 virus evidence some measurable smell dysfunction during its acute phase, although many are unaware of the loss. Long-term deficits occur in up to 30% of COVID-19 cases, although total anosmia is relatively rare. This review explores what is presently known about the nature and pathophysiology of olfactory dysfunction due to the SARS-CoV-2 virus, including reversible inflammation within the olfactory cleft, downregulation of olfactory receptor proteins, and long-lasting peripheral and central damage to olfactory structures. It also addresses the question as to whether long-term smell loss might increase the likelihood of future development of cognitive and neurological deficits.

Vitamin C and its therapeutic potential in the management of COVID19.

COVID19 has emerged as one of the worst pandemics in the history of mankind. Several vaccines have been approved by different government agencies worldwide, but data on their efficacy and safety are limited, and distribution remains a massive challenge. As per WHO, personal immunity is vital for protection against COVID19. Earlier, Vitamin C-mediated pathways have been shown to play critical role in boosting immunity attributed to its antioxidant properties. Recently, the involvement of such pathways in protection against COVID19 has been suggested. The controlled doses of Vitamin C administered through intravenous (IV) injections are being studied for determining its role in the prognosis of COVID19. In this article, we have discussed the potential role of Vitamin C in the management in COVID19 patients and presented recent clinical trials data. Additionally, we have elaborated the possibility of administering Vitamin C through inhalers in order to achieve local high concentration and the challenges of such approach.

Circadian molecular clock disruption in chronic pulmonary diseases.

The circadian clock is the biochemical oscillator with a near 24-h period that is responsible for generating the circadian rhythms in peripheral organs including the lung. Mounting evidence suggests that circadian clock disruption during chronic lung diseases plays an essential role in augmented oxidative stress, inflammatory response, metabolic imbalances, hypoxia/hyperoxia, mucus secretion, dysregulated autophagy, and alters pulmonary function. Here, we review circadian clock disruption and discuss candidate clock genes that are altered at the transcriptional or translational level in chronic pulmonary diseases. This review aims to provide the current knowledge and understanding of the circadian molecular clock disruption in chronic pulmonary diseases which will further advance the development of novel clock-based therapeutics in the future.

Predicting Post-Heart Transplant Composite Renal Outcome Risk in Adults: A Machine Learning Decision Tool

Predicting Post-Heart Transplant Composite Renal Outcome Risk in Adults: A Machine Learning Decision Tool

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Posttraumatic pneumonectomy and management of severely contaminated pleural space.

Temporal Trends in Rural vs Urban Sepsis-Related Mortality in the United States, 2010-2019

Temporal Trends in Rural vs Urban Sepsis-Related Mortality in the United States, 2010-2019

Well-being in the Intensive Care Unit: Looking Beyond COVID-19.

Burnout among critical care personnel has increased due to the additional psychological and physical demands of caring for critically ill patients with limited resources. Factors that increase the risk of burnout include compassion fatigue, lack of control over the work environment, difficult interpersonal relationships, and constant exposure to end-of-life issues. Organizational commitment to physician wellbeing depends on improving workplace efficiency, recognizing stressors in the critical care environment, and providing resources to help manage staffing shortages. Community building, training in communication, and team-building strategies are important steps in building collaboration and camaraderie in the workplace.

Nucleic acid delivery of immune-focused SARS-CoV-2 nanoparticles drives rapid and potent immunogenicity capable of single-dose protection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.

Targeting multiple mediators of sepsis using multifunctional tannic acid-Zn2+-gentamicin nanoparticles

Targeting multiple mediators of sepsis using multifunctional tannic acid-Zn2+-gentamicin nanoparticles