Neuroprotective effects of dantrolene in neurodegenerative disease: Role of inhibition of pathological inflammation.

Neurodegenerative diseases (NDs) refer to a group of diseases in which slow, continuous cell death is the main pathogenic event in the nervous system. Most NDs are characterized by cognitive dysfunction or progressive motor dysfunction. Treatments of NDs mainly target alleviating symptoms, and most NDs do not have disease-modifying drugs. The pathogenesis of NDs involves inflammation and apoptosis mediated by mitochondrial dysfunction. Dantrolene, approved by the US Food and Drug Administration, acts as a RyRs antagonist for the treatment of malignant hyperthermia, spasticity, neuroleptic syndrome, ecstasy intoxication and exertional heat stroke with tolerable side effects. Recently, dantrolene has also shown therapeutic effects in some NDs. Its neuroprotective mechanisms include the reduction of excitotoxicity, apoptosis and neuroinflammation. In summary, dantrolene can be considered as a potential therapeutic candidate for NDs.

Effects of propofol and sevoflurane on T-cell immune function and Th cell differentiation in children with SMPP undergoing fibreoptic bronchoscopy.

OBJECTIVES: The potentially different effects of commonly used anaesthetic agents propofol and sevoflurane on T-cell immune function and Th cell differentiation were investigated in patients with severe mycoplasmal pneumonia (SMPP) undergoing fibreoptic bronchoscopy. METHODS: Sixty children (2-12 years of age) with SMPP were randomized into the sevoflurane group and the propofol group. Patients in the sevoflurane group were anaesthetised with inhalational sevoflurane and intravenous remifentanil. Patients in the propofol group were anaesthetised with intravenous propofol and remifentanil. Patients in both groups underwent fibreoptic bronchoscopy and lavage therapy. We compared the clinical outcomes, cellular immunity function, and Th cell differentiation into Th1 and Th2 levels in both groups. RESULTS: There was no significant difference in clinical outcomes and hospital stay between the two groups (7.94 vs 7.36, p > .05). However, the CD3+ T cells, CD4+ T cells, and CD4+/CD8+ in the propofol group were significantly higher than those in the sevoflurane group (T1 51.96 vs 48.33, T2 58.08 vs 55.31, p < .05). The ratio of Th1/Th2 in the two groups was significantly increased postoperatively in both groups (Sevoflurane 8.53 vs 7.23, Propofol 9.35 vs 7.18), and the propofol group was significantly higher than the sevoflurane group (9.35 vs 8.53, p < .05). CONCLUSIONS: Propofol might have a less inhibitory effect on T lymphocytes in children with SMPP than sevoflurane. And propofol may have less impact on the differentiation of Th cells into Th1 cells and better preserving the Th1/Th2 ratio than sevoflurane. KEY MESSAGESThe pathogenesis of SMPP is still unclear, likely through alveolar infiltration with neutrophils and lymphocytes, lymphocyte/plasma cell infiltrates in the peri-bronchovascular area, and immune dysfunction.Recent experimental and clinical studies showed that sevoflurane might have immunosuppressive effects, and multiple studies confirmed that the immune function of children with SMPP had been reduced.This study found that propofol administered in children with SMPP had a less inhibitory effect on T lymphocytes than inhalational sevoflurane, had little inhibitory effect on the differentiation of Th cells into Th1 cells, and better preserve Th1/Th2 ratio and maintain the balanced immune function.

Anticoagulation with Argatroban in a Patient with Heparin-Induced Thrombocytopenia and Renal Insufficiency Undergoing Orthotopic Heart Transplantation.

Unfractionated heparin is the anticoagulant of choice for cardiac surgery that requires cardiopulmonary bypass. However, it can cause serious side effects like heparin-induced thrombocytopenia (HIT), an immune-mediated process where antibodies are directed against heparin and platelet 4 complexes. In such cases, alternative pharmacologic strategies are implemented to facilitate safe bypass conditions. A woman with severe decompensated heart failure was heparinized for intra-aortic balloon pump and subsequent LVAD placement. On day 6, a fall in platelets from 113,000 to 26,000 was noted. She was diagnosed with HIT. Heparin was discontinued and replaced with an argatroban infusion for the duration of her care until heart transplantation was completed. We review the mechanism, diagnosis, and complications of HIT. We discuss cardiopulmonary bypass and its relation to heparin, HIT, and heparin alternatives. We discuss argatroban's relevant pharmacology, clinical use, advantages, and disadvantages.

Economic impact of COVID-19 pandemic on healthcare facilities and systems: International perspectives.

International hospitals and healthcare facilities are facing catastrophic financial challenges related to the COVID-19 pandemic. The American Hospital Association estimates a financial impact of $202.6 billion in lost revenue for America's hospitals and healthcare systems, or an average of $50.7 billion per month. Furthermore, it could cost low- and middle-income countries ~ US$52 billion (equivalent to US$8.60 per person) each four weeks to provide an effective healthcare response to COVID-19. In the setting of the largest daily COVID-19 new cases in the US, this burden will influence patient care, surgeries, and surgical outcomes. From a global economic standpoint, The World Bank projects that global growth is projected to shrink by almost 8% with poorer countries feeling most of the impact, and the United Nations projects that it will cost the global economy around 2 trillion dollars this year. Overall, a lack of preparedness was a major contributor to the struggles experienced by healthcare facilities around the world. Items such as personal protective equipment (PPE) for healthcare workers, hospital equipment, sanitizing supplies, toilet paper, and water were in short supply. These deficiencies were exposed by COVID-19 and have prompted healthcare organizations around the world to invent new essential plans for pandemic preparedness. In this paper, we will discuss the economic impact of COVID-19 on US and international hospitals, healthcare facilities, surgery, and surgical outcomes. In the future, the US and countries around the world will benefit from preparing a plan of action to use as a guide in the event of a disaster or pandemic.

Anesthetic management of thoracoscopic procedures in neonates: a retrospective analysis of 45 cases.

BACKGROUND: Advances in medical techniques and equipment have enabled the thoracoscopic repair of certain congenital abnormalities in neonates including congenital esophageal atresia/tracheoesophageal fistula (EA/TEF) and congenital diaphragmatic hernia (CDH). A retrospective analysis was conducted to examine the anesthetic management of neonates (7 days or younger) undergoing thoracoscopic surgery in our hospital department, and to determine the efficacy of anesthetic management in neonates. METHODS: Clinical data from 45 neonates who underwent thoracoscopic surgery in our hospital from December 2015 to March 2020 were retrospectively analyzed. A total of 25 patients underwent repair of CDH and 20 underwent repair of an EA/TEF. RESULTS: All patients received general anesthesia with endotracheal intubation, standard ASA monitoring, and arterial blood gas (ABG) analysis. All patients survived the surgery. A total of 14 patients experienced decreases in SpO2, pH, PaO2, and increases in PETCO2 and PaCO2 30 minutes after CO2 insufflation. Our anesthetic management protocols are outline and analyzed. CONCLUSIONS: Thorough preoperative preparation is critical for a desirable outcome in neonates undergoing a thoracoscopic repair of CDH or EA/TEF. In our cohort, intraoperative ventilation strategies included pressure control ventilation with peak airway pressure maintained at 15-25 cmH2O, a respiratory rate of 35-55 breaths/minute, a fraction of inspired oxygen (FiO2) of 60-80%, an inspiratory/expiratory ratio (I:E) of 1:1-1.5, and careful airway suctioning to clear secretions. Postoperatively, maintaining normovolemia and hemodynamic stability are critical for successful weaning of ventilatory support and extubation.

The Application of Fascia Iliaca Compartment Block for Acute Pain Control of Hip Fracture and Surgery.

PURPOSE OF REVIEW: Over 300,000 patients are hospitalized annually following hip fractures in the USA. Many patients experienced inadequate analgesia. We will review the perioperative effects of the fascia iliaca compartment block (FICB) in hip fracture patients. RECENT FINDINGS: FICB by injecting local anesthetics beneath the fascia iliaca results in significant pain relief in hip fractures. Neuropathies and vascular injuries are almost unlikely. Single-shot FICB is faster to place, yet providing about 8 h of analgesia when bupivacaine is used. Continuous FICB provides prolonged titratable analgesia, improved patient satisfaction, and leads to faster hospital discharge. FICB reduces opioid consumption, decreases morbidity and mortality, reduces hospital stay, reduces delirium, and improves satisfaction. FICB should form part of a multimodal analgesic regime, in the context of a multidisciplinary approach to the management of hip fracture patients. More clinical investigations are needed to validate the long-term outcome benefits of FICB in hip fracture patients.

Measuring the teamwork performance of operating room teams: a systematic review of assessment tools and their measurement properties.

Teamwork is fundamental to surgical patient safety but is inconsistently measured. While many tools have been developed for elective intraoperative situations, it is unclear which is the most robust. This systematic review aimed to identify tools to measure the teamwork of operating room teams. Studies were included if they examined the measurement properties of these tools. PsycINFO, Embase (via OVID), CINAHL, ERIC, Medline and Medline in Process (via OVID) were searched through to May 3, 2019, as were reference lists of included studies and previously published relevant reviews. Retrieved articles were screened and data extracted in duplicate by two independent reviewers. Quality was assessed using the COSMIN checklist. Of the 2121 references identified, 14 studies of six assessment tools were included. Tools were validated across various specialties, mostly in clinical rather than simulated settings. The Observational Teamwork Assessment for Surgery (OTAS) and Operating Theater Team Non-Technical Skills Assessment Tool (NOTECHS) were the most frequently investigated tools. Though acceptable for assessing teamwork, both NOTECHS and OTAS rely on the questionable assumption that the teamwork of a team is equivalent to the sum of individual performances. Future studies may investigate other assessment tools that assess the whole team as the unit of analysis along with the potential of these tools to provide healthcare providers with meaningful feedback in clinical practice.

Intraoperative Laryngeal Mask Airway-Related Hiccup: An Overview.

Hiccup is an involuntary contraction of the diaphragm and intercostal muscles resulting in sudden inspiration and closure of the glottis. The presence of hiccup in the perioperative period can be a challenging problem. Sudden movements of the patient from hiccups can interfere preoperative diagnostic procedures, intraoperative hiccup may delay the beginning of surgery, interfere with the surgical process, and affect intraoperative monitoring, and postoperative hiccup may affect would healing and hemodynamic stability. Hiccup can lead to have increased aspiration risk. Hiccup are is an incompletely understood phenomenon with multiple etiologies. Intraoperative hiccup related to laryngeal mask airway placement has been reported, and it presents unique challenges in diagnosis and management. Both pharmacological and non-pharmacological interventions have been utilized with various level of success. All treatment strategies are primarily aimed at interrupting the hiccup reflex arc.

Regional anesthesia considerations for cardiac surgery.

Pain is a significant consequence of cardiac surgery and newer techniques in cardiac anesthesia have provided an impetus for the development of multimodal techniques to manage acute pain in this setting. In this regard, regional anesthesia techniques have been increasingly used in many cardiac surgical procedures, for the purposes of reducing perioperative consumption of opioid agents and enhanced recovery after surgery. The present investigation focuses on most currently used regional techniques in cardiac surgical procedures. These regional techniques include chest wall blocks (e.g., PECS I and II, SAP, ESB, PVB), sternal blocks (e.g., TTMPB, PSINB), and neuraxial blocks (e.g., TEA, high spinal anesthesia). The present investigation also summarizes indications, technique, complications, and potential clinical benefits of these evolving regional techniques. Cardiac surgery patients may benefit from application of these regional techniques with well controlled indications and careful patient selections.

Thymoma associated paraneoplastic encephalitis (TAPE), a potential cause of limbic encephalitis.

A 59-year-old man presents with expressive aphasia and short term memory deficits. Shortly thereafter, he started developing staring spells and intermittent right hand spasms, preliminarily thought to be simple partial seizures. Subsequent MRI brain imaging was highly suggestive of herpes simplex virus (HSV) encephalitis; however, HSV PCR from cerebrospinal fluid was negative. On further testing, the patient was found to have an autoimmune encephalitis thought to be related to an incidentally found thymoma. His clinical presentation, in conjunction with imaging and response to therapy, was strongly suggestive of thymoma associated paraneoplastic encephalitis. Early recognition is the only way to ensure prompt initiation of appropriate treatment. Immunotherapy and cancer directed therapy (including tumour resection, if indicated) have been shown to have favourable outcomes, improved speed of neurological recovery and reduced risk of relapses. Without treatment, progressive neurologic deterioration can occur over months to years, eventually resulting in death.

Preoperative patient preparation in enhanced recovery pathways.

Enhanced recovery pathways are a novel approach focused on enhancing the care of surgical patients. "Prehabilitation" is the term applied to any intervention administered before surgery to reduce surgery-related morbidity, decrease the length of hospital stay, expedite the return of organ function, and facilitate the patient's return to normal life. A PubMed search was performed with the following key words: enhanced recovery, preoperative preparation, cessation of smoking and euvolemia. The results from this Pubmed search revealed that female patients may have higher levels of anxiety than male patients. Intensive smoking and alcohol cessation 6-8 weeks before elective surgery may reduce the incidence of postoperative morbidity. Preoperative exercise can be effective for reducing the postoperative complications like pulmonary complications and shortening the length of hospital stay. It is safe to allow patients to drink clear fluids up until 2 h before elective surgery (Level II evidence). Perioperative normoglycemia is the single most important factor to prevent surgical site infection. Intermittent pneumatic compression devices and low molecular weight heparin are effective in preventing postoperative thromboembolism. No advantage is gained by preoperative mechanical bowel preparation in elective colorectal surgery. The goal of preoperative fluid management is for the patient to arrive in the operating room in a hydrated and euvolemic state. Mild perioperative hypothermia may promote surgical wound infection by triggering thermoregulatory vasoconstriction, which decreases subcutaneous oxygen tension.

Goal-directed fluid therapy in the perioperative setting.

Improvement in patient outcomes has become a significant consideration with our limited resources in the surgical setting. The implementation of enhanced recovery pathway protocols has resulted in significant benefits to both the patients and hospitals, such as shorter length of hospital stays, reduction in the rate of complications, and fewer hospital readmissions. An emerging component and a key element for the success of Enhanced Recovery After Surgery (ERAS) protocols has been the concept of goal-directed fluid therapy (GDT). GDT related to ERAS protocols attempts to minimize complications associated with fluid imbalance during surgery. We performed a literature search for articles that included the terms enhanced recovery and GDT. We evaluated methods for appropriate volume status assessment, such as heart rate, blood pressure, end-tidal CO2, central venous pressure, urine output, stroke volume, cardiac output, and their derivatives. Some invasive, minimally invasive, and non-invasive monitors of hemodynamic evaluation are now being used to assess volume status and predict fluid responsiveness and fluid need during various surgical procedures. Regardless of monitoring technique, it is important for the clinician to effectively plan and implement preoperative and intraoperative fluid goals. Excess crystalloid fluid should be avoided. In some low-risk patients undergoing low-risk surgery, a "zero-balance" approach is encouraged. For the majority of patients undergoing major surgery, GDT is recommended. Optimal perioperative fluid management is an important component of the ERAS pathways and it can reduce postoperative complications.

Enhanced Recovery Pathways for Cardiac Surgery.

PURPOSE OF REVIEW: Enhanced recovery after surgery (ERAS) has become a widespread topic in perioperative medicine over the past 20 years. The goals of ERAS are to improve patient outcomes and perioperative experience, reduce length of hospital stay, minimize complications, and reduce cost. Interventions and factors before, during, and after surgery all potentially play a role with the cumulative effect being superior quality of patient care. RECENT FINDINGS: Preoperatively, patient and family education, optimization of nutritional status, and antibiotic prophylaxis all improve outcomes. Recovery is also expedited by the use of multimodal analgesia, regional anesthesia, and opioid reducing approaches. Intraoperatively, the anesthesiologist can have an impact by using less-invasive monitors appropriately to guide fluid and hemodynamic management as well as maintaining normothermia. Postoperatively, early enteral feeding, mobilization, and removal of invasive lines support patient recovery. Implementation of ERAS protocol in cardiac surgery faces challenges by some unique perioperative perspectives in cardiac surgery, such as systemic anticoagulation, use of cardiopulmonary bypass, significantly more hemodynamic variations, larger volume replacement, postoperative intubation and mechanical ventilation and associated sedation, and potentially significantly more co-existing morbidities than other surgical procedures. ERAS in cardiac surgery may benefit patients more related to its high risk and high cost nature. This manuscript specifically reviews the unique aspects of enhanced recovery in cardiac surgery.

Machine learning model to predict recurrent ulcer bleeding in patients with history of idiopathic gastroduodenal ulcer bleeding.

BACKGROUND: Patients with a history of Helicobacter pylori-negative idiopathic bleeding ulcers have an increased risk of recurring ulcer complications. AIM: To build a machine learning model to identify patients at high risk for recurrent ulcer bleeding. METHODS: Data from a retrospective cohort of 22 854 patients (training cohort) diagnosed with peptic ulcer disease in 2007-2016 were analysed to build a model (IPU-ML) to predict recurrent ulcer bleeding. We tested the IPU-ML in all patients with a diagnosis of gastrointestinal bleeding (n = 1265) in 2008-2015 from a different catchment population (independent validation cohort). Any co-morbid conditions which had occurred in >1% of study population were eligible as predictors. RESULTS: Recurrent ulcer bleeding developed in 4772 patients (19.5%) in the training cohort, during a median follow-up period of 2.7 years. IPU-ML model built on six parameters (age, baseline haemoglobin, and presence of gastric ulcer, gastrointestinal diseases, malignancies, and infections) identified patients with bleeding recurrence within 1 year with an area under the receiver operating characteristic curve (AUROC) of 0.648. When we set the IPU-ML cutoff value at 0.20, 27.5% of patients were classified as high risk for rebleeding with a sensitivity of 41.4%, specificity of 74.6%, and a negative predictive value of 91.1%. In the validation cohort, the IPU-ML identified patients with a recurrence ulcer bleeding within 1 year with an AUROC of 0.775, and 84.3% of overall accuracy. CONCLUSION: We developed a machine-learning model to identify those patients with a history of idiopathic gastroduodenal ulcer bleeding who are not at high risk for recurrent ulcer bleeding.

Long-term follow-up of torsional augmentation surgery in a case of congenital ocular tilt reaction with head tilt.

Torsional augmentation surgery was used to correct the anomalous head position (AHP) in a child with congenital ocular tilt reaction (OTR). The underlying neuropathology was hypoplasia involving the right hemicerebellum and contralateral brainstem. Postoperatively there was an acceptable and variable resolution of head tilt sustained over a 25-year follow-up period. These findings suggest that early torsional augmentation surgery can effectively correct stable OTR head tilt in congenital cases over the long term.

Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) is rapidly increasing due to the prevalence of obesity and non-alcoholic fatty liver disease, but the molecular triggers that initiate disease development are not fully understood. We demonstrate that mice with targeted loss-of-function point mutations within the AMP-activated protein kinase (AMPK) phosphorylation sites on acetyl-CoA carboxylase 1 (ACC1 Ser79Ala) and ACC2 (ACC2 Ser212Ala) have increased liver de novo lipogenesis (DNL) and liver lesions. The same mutation in ACC1 also increases DNL and proliferation in human liver cancer cells. Consistent with these findings, a novel, liver-specific ACC inhibitor (ND-654) that mimics the effects of ACC phosphorylation inhibits hepatic DNL and the development of HCC, improving survival of tumor-bearing rats when used alone and in combination with the multi-kinase inhibitor sorafenib. These studies highlight the importance of DNL and dysregulation of AMPK-mediated ACC phosphorylation in accelerating HCC and the potential of ACC inhibitors for treatment.

Novel Rescue Strategy for Endotracheal Intubation Through Severe Subglottic Stenosis by Using a Metal Suction Tube as a Tube Stylet in a Neonate: A Case Report.

We report a novel technique for the management of subglottic stenosis in a neonate. The initial endotracheal intubation did not provide adequate mechanical ventilation due to a significant air leak. We then performed suspension laryngoscopy and used a metal suction tube as an intubating stylet. We successfully inserted an endotracheal tube deep enough to maintain adequate mechanical ventilation. This technique is a viable rescue strategy in this clinical scenario.