Clinical impact of physician staffing transition in intensive care units: a retrospective observational study.

BACKGROUND: Intensivists play an essential role in improving the outcomes of critically ill patients in intensive care units (ICUs). The transition of ICU physician staffing from low-intensity ICUs (elective intensivist or no intensivist consultation) to high-intensity ICUs (mandatory intensivist consultation or a closed ICU) improves clinical outcomes. However, whether a transition from high-intensity to low-intensity ICU staffing affects ICU outcomes and quality of care remains unknown. METHODS: A retrospective observational study was conducted to examine the impact of high- versus low-intensity staffing models on all-cause mortality in a suburban secondary community hospital with 400 general beds and 8 ICU beds. The ICU was switched from a high-intensity staffing model (high-former period) to low-intensity staffing in July 2019 (low-mid period) and then back to high-intensity staffing in March 2020 (high-latter period). Patients admitted from the emergency department, general ward, or operating room after emergency surgery were enrolled in these three periods and compared, balancing the predicted mortality and covariates of the patients. The primary outcome was all-cause mortality analyzed using hazard ratios (HRs) from Cox proportional hazards regression. An interrupted time-series analysis (ITSA) was also conducted to evaluate the effects of events (level change) and time. RESULTS: There were 962 eligible admissions, of which 251, 213, and 498 occurred in the high-former, low-mid, and high-latter periods, respectively. In the matched group (n = 600), the all-cause mortality rate comparing the high-former period with the low-mid period showed an HR of 0.88 [95% confidence interval (CI), 0.56, 1.39; p = 0.58] and that comparing the high-latter period with the low-mid period showed an HR of 0.84 [95% CI, 0.54, 1.30; p = 0.43]. The result for comparison between the three periods was p = 0.80. ITSA showed level changes of 4.05% [95% CI, -13.1, 21.2; p = 0.63] when ICU staffing changed from the high-former to the low-mid period and 1.35% [95% CI, -13.8, 16.5; p = 0.86] when ICU staffing changed from the low-mid to the high-latter period. CONCLUSION: There was no statistically significant difference in all-cause mortality among the three ICU staffing periods. This study suggests that low-intensity ICU staffing might not worsen clinical outcomes in the ICU in a medium-sized community hospital. Multiple factors, including the presence of an intensivist, other medical staff, and practical guidelines, influence the prognosis of critically ill patients.

Pulmonary vein thrombosis and cerebral infarction after video-assisted thoracic surgery of the left upper lobe: a case series.

BACKGROUND: Pulmonary vein thrombosis (PVT) and cerebral infarction are rare but critical complications after video-assisted thoracic surgery (VATS). CASE PRESENTATION: We experienced two cases of massive middle cerebral artery infarction after VATS for the left upper lobe. Although the precise source of their embolus was never identified, both cases were clinically suspected PVT. Unfortunately, case 2 died because of progressive cerebral herniation. We decided to perform contrast-enhanced computed tomography routinely after VATS for the left upper lobectomy (VATS-LUL) after these cases. Case 3, a 79-year-old female patient, underwent VATS-LUL for lung cancer. She developed PVT in the stump of the left upper pulmonary vein on postoperative day 4. Anti-coagulation therapy was begun immediately and continued for 3 months. She was free of complications 7 months after the operation. CONCLUSION: PVT and cerebral infarction may occur after VATS-LUL. Appropriate postoperative management is required to recognize PVT and to prevent life-threatening stroke.

Kinase-kinase interaction and modulation of tau phosphorylation.

The microtubule (MT)-associated protein tau attaches to neuronal MT networks and regulates their integrity. The phosphorylation state of tau alters its binding activity. MT integrity is maintained by the phosphorylation state of tau, which is under the control of the kinase-phosphatase balance. This control requires the proper regulation of topographical and temporal characteristics of tau kinases and phosphatases. The tau phosphorylation protein complex (TPPC) anchors tau kinases and phosphatases via scaffold proteins, tau effectors, and tau itself. Targeting these proteins in TPPC fulfills the topographical requirements for maintaining MT functions. The switching of tau kinase activity determines the order of the kinase action. The combined action of kinases is temporally modulated; reversal of the time order of events results in a differential state of tau phosphorylation. Elucidation of protein-protein interaction in the regulation of tau phosphorylation will shed light on the physiology and pathology of tau phosphorylation.

[Anesthetic management of undiagnosed pheochromocytoma: a case report].

A 55-year-old man was scheduled for resection of an adrenal tumor under the diagnosis of a non-functioning adrenal tumor. He was admitted for unstable angina 58 days preoperatively, and on the second hospital day, he had an episode of ventricular tachycardia for 20 seconds following epigastric pain. Abdominal computed tomography scans revealed a retroperitoneal abscess, which was subsequently drained effectively, and a right adrenal tumor. Because of the almost normal plasma catecholamine concentration, the tumor was considered a nonfunctioning tumor. However, when the surgeon manipulated the tumor during the operation, the patient's blood pressure increased suddenly to 240/120 mmHg. The hypertensive crisis was managed with nicardipine and phentolamine. After resection of the tumor, his blood pressure decreased to 80/40 mmHg, and the patient was treated with ephedrine, phenylephrine, and noradrenaline. After surgery, the tumor was confirmed histopathologically as a pheochromocytoma. The management of patients with a hypertensive crisis under suspicion of pheochromocytoma is discussed.

[Awareness during anesthesia with sevoflurane: a case report].

We report a case of a patient who experienced awareness during general anesthesia with sevoflurane. A 71-year-old man, weighing 57 kg, was operated on for a malignant tumor of the parotid gland. He was given 2 mg diazepam orally as a premedication. General anesthesia was induced by thiamylal 200 mg, fentanyl 50 microg, and up to 5% of sevoflurane. Muscle relaxation was obtained with vecuronium 6 mg, and the patient was intubated. After induction, fentanyl 150 microg was added, but no other intravenous anesthetics or muscle relaxants were used. The end-expiratory concentration of sevoflurane was maintained at 0.8% to 1.7% before the start of surgery, and 1.5% to 2.9% during surgery. The operation lasted for 10.4 hours. His left eye was guarded by ointment but kept open for observation by the surgeon of facial movement following muscle stimulation. The surgical course, emergence, and the postoperative course were uneventful. On the fifth postoperative day, the patient started to describe his visual memory during the operation, although he did not remember any pain or discomfort. We believe that visual input through his open eyes, the effect of cranial bone oscillation by the surgery, and the idiosyncrasy of the patient contributed to his intraoperative recall.

Potentiation of proopiomelanocortin gene expression in cultured pituitary cells by benzodiazepines.

BACKGROUND: Benzodiazepines are frequently used not only as a part of general anesthesia but also for the purpose of sedation during regional anesthesia. Effects of these drugs on the hypothalamic-pituitary-adrenal axis activity have been studied, but are still controversial. It is not known whether benzodiazepines affect expression of proopiomelanocortin, precursor protein of adrenocorticotropic hormone and related peptides. METHODS: AtT20PL cell line, a clone of AtT20/D16v mouse corticotroph tumor cells stably transfected with approximately 0.7 kilobases (kb) of the rat proopiomelanocortin 5' promoter-luciferase fusion gene, was used. In the presence or absence of diazepam or midazolam, cells were stimulated by corticotropin-releasing hormone (CRH) or forskolin. Proopiomelanocortin gene expression was estimated by measurement of luciferase activity. Furthermore, to study the mechanism of benzodiazepine effects, cyclic adenosine 3',5'-monophosphate (cyclic AMP) efflux was measured by enzyme immunoassay. RESULTS: Diazepam and midazolam dose-dependently increased the proopiomelanocortin gene expression induced by CRH or forskolin. The potentiating effect was not affected by benzodiazepine receptor antagonists flumazenil and PK11195, but was abolished by a cyclic AMP-dependent protein kinase inhibitor H89. Cyclic AMP efflux induced by CRH or forskolin was also enhanced by diazepam and midazolam. In the presence of isobutylmethylxanthine, a nonspecific phosphodiesterase inhibitor, potentiation of proopiomelanocortin gene expression and enhancement of cyclic AMP efflux by benzodiazepines were not observed. CONCLUSIONS: Benzodiazepines potentiate the effect of CRH or forskolin on proopiomelanocortin gene expression. The potentiating effect is not mediated by the benzodiazepine receptors, but its mechanism probably involves inhibition of phosphodiesterase.

Truncation of CDK5 activator p35 induces intensive phosphorylation of Ser202/Thr205 of human tau.

Hyperphosphorylated tau is a major component of neurofibrillary tangles, one of the hallmarks of Alzheimer's disease. CDK5 is a kinase that phosphorylates the tau protein, and its endogenous activator, p35, regulates its activity. Recently, calpain was found to digest p35 to its truncated product, p25. Several lines of evidence suggest that p25-CDK5 has much more powerful kinase activity and that it may cause abnormal hyperphosphorylation of tau. In this study, we have examined the kinetic characteristics of in vitro phosphorylation of the longest isoform of human tau by CDK5 and its activators using recombinant proteins. Although the kinase activity of CDK5 in phosphorylating tau was significantly higher in the presence of p25, the affinity of CDK5 for tau was not different. Phosphopeptide mapping revealed enhanced phosphorylation of Ser(202)/Thr(205) residues by p25-CDK5 (amino acid residues of tau are numbered according to the longest isoform of human tau). These results suggest that cleavage of p35 to p25 greatly enhances the kinase activity of CDK5 and increases the phosphorylation of Ser(202)/Thr(205). Considering the fact that phosphorylation of Ser(202)/Thr(205) antagonizes the tau-mediated nucleation of tubulin, p25-CDK5 may play a pivotal role in neuronal cell death in Alzheimer's disease.