Pkm2 Regulates Cardiomyocyte Cell Cycle and Promotes Cardiac Regeneration.

BACKGROUND: The adult mammalian heart has limited regenerative capacity, mostly attributable to postnatal cardiomyocyte cell cycle arrest. In the last 2 decades, numerous studies have explored cardiomyocyte cell cycle regulatory mechanisms to enhance myocardial regeneration after myocardial infarction. Pkm2 (Pyruvate kinase muscle isoenzyme 2) is an isoenzyme of the glycolytic enzyme pyruvate kinase. The role of Pkm2 in cardiomyocyte proliferation, heart development, and cardiac regeneration is unknown. METHODS: We investigated the effect of Pkm2 in cardiomyocytes through models of loss (cardiomyocyte-specific Pkm2 deletion during cardiac development) or gain using cardiomyocyte-specific Pkm2 modified mRNA to evaluate Pkm2 function and regenerative affects after acute or chronic myocardial infarction in mice. RESULTS: Here, we identify Pkm2 as an important regulator of the cardiomyocyte cell cycle. We show that Pkm2 is expressed in cardiomyocytes during development and immediately after birth but not during adulthood. Loss of function studies show that cardiomyocyte-specific Pkm2 deletion during cardiac development resulted in significantly reduced cardiomyocyte cell cycle, cardiomyocyte numbers, and myocardial size. In addition, using cardiomyocyte-specific Pkm2 modified RNA, our novel cardiomyocyte-targeted strategy, after acute or chronic myocardial infarction, resulted in increased cardiomyocyte cell division, enhanced cardiac function, and improved long-term survival. We mechanistically show that Pkm2 regulates the cardiomyocyte cell cycle and reduces oxidative stress damage through anabolic pathways and ß-catenin. CONCLUSIONS: We demonstrate that Pkm2 is an important intrinsic regulator of the cardiomyocyte cell cycle and oxidative stress, and highlight its therapeutic potential using cardiomyocyte-specific Pkm2 modified RNA as a gene delivery platform.

Nonpharmacologic and Medication Minimization Strategies for the Prevention and Treatment of ICU Delirium: A Narrative Review.

Delirium is a multifactorial entity, and its understanding continues to evolve. Delirium has been associated with increased morbidity, mortality, length of stay, and cost for hospitalized patients, especially for patients in the intensive care unit (ICU). Recent literature on delirium focuses on specific pharmacologic risk factors and pharmacologic interventions to minimize course and severity of delirium. While medication management clearly plays a role in delirium management, there are a variety of nonpharmacologic interventions, pharmacologic minimization strategies, and protocols that have been recently described. A PubMed search was performed to review the evidence for nonpharmacologic management, pharmacologic minimization strategies, and prevention of delirium for patients in the ICU. Recent approaches were condensed into 10 actionable steps to manage delirium and minimize medications for ICU patients and are presented in this review.

Psychosocial impact of cancer on adult patients.

OBJECTIVES: To explore the effects of cancer on psychosocial aspects of Pakistani patients and their families, assessing the need for interventions to improve their quality of life. METHODS: A prospective, Cross-sectional study was performed on 200 patients visiting the oncology outpatient facility of AKUH from December 2010 to May 2011 through an interview. Responses were recorded on pre-designed questionnaires including FACT-G QOL (Functional Assessment of Cancer Therapy-General Quality Of Life) component. RESULTS: Out of the 200 patients 52 (26%) were males and 148 (74%) were females. Mean age was 51.8 +/- 14.2 years. Breast cancer accounted for the commonest cancer in females 116 (58%) and lung in males 30 (15%), 100 (50%) patients were currently undergoing chemotherapy. In all 148 (74%) patients were well aware of their diagnosis and were able to cope better and 142 (71%) were well supported by families (majority being financially stable). Major financial impact was found in 42 (21%) cases. Religious/spiritual help was sought by 138 (69%) patients predominantly females- 113 (76%) and 22 (11%) patients consulted a psychiatrist; 20 (94%) subjects of this group felt this intervention was helpful. Responses regarding effect on the patient's sexual life were poor and 126 (63%) denied answering the question. CONCLUSION: In our study one third of cancer patients were found to be depressed mainly affecting those who were receiving multimodality treatment or facing financial issues. Religious help was the main coping strategy for them.

Thyroid Storm in a Patient on Chronic Amiodarone Treatment.

Amiodarone is a class III antiarrhythmic drug with a structure comparable to thyroid hormone and 37% iodine content by weight. In addition to direct drug cytotoxicity on thyroid cells, amiodarone deiodination in the body releases an excessive amount of iodine, which can impair thyroid function and cause hypothyroidism or thyrotoxicosis, including thyroid storm in susceptible individuals. In this report, we discuss the case of a 52-year-old woman who experienced a thyroid storm after being treated with amiodarone, eventually leading to her death.

COVID-19-Associated Tension Pneumothorax in Mechanically Ventilated Patients: A Case Series.

Severe acute respiratory syndrome management secondary to coronavirus (SARS-CoV-2) has been overwhelming for healthcare systems. Patients with SARS-CoV-2 infection can present with symptoms ranging from a mild flu-like illness to acute respiratory distress syndrome (ARDS). Patients who develop coronavirus disease 2019 (COVID-19) infection and present with hypoxic respiratory failure requiring mechanical ventilation typically follow ARDS physiology. Many of them develop complications including pneumothorax, pneumomediastinum, and pneumopericardium. In this case series, we present multiple instances where patients with severe COVID-19 infections developed tension pneumothoraces during their hospital course.

COVID-19-Associated Spontaneous Pneumomediastinum and Pneumopericardium: Review of Case Series.

Coronavirus disease 2019 (COVID-19) and its spectrum of respiratory illnesses ranging from mild to severe and critically ill have been well established. Spontaneous pneumomediastinum and pneumopericardium (PP) appear to be less reported entities and have been found to be reported complications in COVID-19 infection. Pneumomediastinum (PM) and PP are characterized by the presence of air in the mediastinal and pericardial cavity, respectively. Although, generally, secondary to trauma or underlying lung conditions like asthma, bronchiolitis obliterans, and blunt trauma, it can also occur spontaneously without an evident primary cause. PM and PP are increasingly reported complications in COVID-19 patients adversely affecting clinical outcomes. We present a case series of patients with spontaneous pneumomediastinum and pneumopericardium in the presence of underlying COVID-19 infection and their management at our academic medical center.

Tocilizumab for the Treatment of COVID-19-Induced Cytokine Storm and Acute Respiratory Distress Syndrome: A Case Series From a Rural Level 1 Trauma Center in Western Pennsylvania.

An outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2, initially in December 2019 at Wuhan, China, subsequently spread around the world. We describe a case series of COVID-19 patients treated at our academic medical center with focus on cytokine storm and potential therapeutic role of tocilizumab. A 59-year-old female admitted for shortness of breath (SOB), productive cough, fever, and nausea in the setting of COVID-19 pneumonia. Oxygen saturation was 81% necessitating supplemental oxygen. She was transferred to intensive care unit (ICU) for worsening hypoxia; intubated and received tocilizumab following which her oxygen requirements improved. A 52-year-old female admitted from an outside hospital with SOB, intubated for worsening hypoxia, in the setting of COVID-19 pneumonia. She received tocilizumab 400 mg intravenous for 2 doses on ICU admission, with clinical improvement. A 56-year-old female hospitalized with worsening SOB, fever, and cough for 8 days saturating 88% on room air in the setting of COVID-19 pneumonia. Worsening hypoxia necessitated high flow nasal cannula. She was transferred to the ICU where she received 2 doses of tocilizumab 400 mg intravenous. She did not require intubation and was transitioned to nasal cannula. A hyperinflammatory syndrome may cause a life-threatening acute respiratory distress syndrome in patients with COVID-19 pneumonia. Tocilizumab is the first marketed interleukin-6 blocking antibody, and through targeting interleukin-6 receptors likely has a role in treating cytokine storm. We noted clinical improvement of patients treated with tocilizumab.

Assessment of acute head injury in an emergency department population using sport concussion assessment tool - 3rd edition.

Sport Concussion Assessment Tool version 3 (SCAT-3) is one of the most widely researched concussion assessment tools in athletes. Here normative data for SCAT3 in nonathletes are presented. The SCAT3 was administered to 98 nonathlete healthy controls, as well as 118 participants with head-injury and 46 participants with other body trauma (OI) presenting to the ED. Reference values were derived and classifier functions were built to assess the accuracy of SCAT3. The control population had a mean of 2.30 (SD = 3.62) symptoms, 4.38 (SD = 8.73) symptom severity score (SSS), and 26.02 (SD = 2.52) standardized assessment of concussion score (SAC). Participants were more likely to be diagnosed with a concussion (from among healthy controls) if the SSS > 7; or SSS ≤ 7 and SAC ≤22 (sensitivity = 96%, specificity = 77%). Identification of head injury patients from among both, healthy controls and body trauma was possible using rule SSS > 7 and headache or pressure in head present, or SSS ≤ 7 and SAC ≤ 22 (sensitivity = 87%, specificity = 80%). In this current study, the SCAT-3 provided high sensitivity to discriminate acute symptoms of TBI in the ED setting. Individuals with a SSS > 7 and headache or pressure in head, or SSS ≤ 7 but with a SAC ≤ 22 within 48-hours of an injury should undergo further testing.

Actual and projected incidence rates for chronic subdural hematomas in United States Veterans Administration and civilian populations.

OBJECT: Chronic subdural hematomas (SDHs) are more common among veterans and elderly persons than among members of the general population; however, precise incidence rates are unknown. The purposes of this study were 1) to determine the current incidence of chronic SDH in a US Veterans Administration (VA) population and 2) to create a mathematical model for determining the current and future incidence of chronic SDH as a function of population age, sex, and comorbidity in the United States VA and civilian populations. METHODS: To determine the actual number of veterans who received a radiographic diagnosis and surgical treatment for SDH during 2000-2012, the authors used the VISN03 VA database. On the basis of this result and data from outside the United States, they then created a mathematical model accounting for age, sex, and alcohol consumption to predict the incidence of SDH in the VA and civilian populations during 2012-2040. RESULTS: Of 875,842 unique (different patient) visits to a VA hospital during the study period, 695 new SDHs were identified on CT images. Of these 695 SDHs, 203 (29%) required surgical drainage. The incidence rate was 79.4 SDHs per 100,000 persons, and the age-standardized rate was 39.1±4.74 SDHs per 100,000 persons. The authors' model predicts that incidence rates of chronic SDH in aging United States VA and civilian populations will reach 121.4 and 17.4 cases per 100,000 persons, respectively, by 2030, at which time, approximately 60,000 cases of chronic SDH will occur each year in the United States. CONCLUSIONS: The incidence of chronic SDH is rising; SDH is projected to become the most common cranial neurosurgical condition among adults by the year 2030.

Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion.

Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 sec and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy noninjured control subjects and compared findings to 75 trauma subjects with either a positive head computed tomography (CT) scan (n=13), negative head CT (n=39), or nonhead injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure Sport Concussion Assessment Tool 3 (SCAT3) in trauma patients. Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to noninjured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain-injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion score. Abnormal eye-tracking metrics improved over time toward baseline in brain-injured subjects observed in follow-up. Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury.