2018年·第98卷第44期

Good sleep is necessary for the existence of life, and it is especially important for critically ill patients. Sleep disorders not only affect the treatment of patients, but also prolong the stay time of patients in intensive care unit (ICU) and overall hospital stay, and in severe cases, they can increase the risk of death. Most critically ill patients need to be treated in ICU. These patients generally suffer from sleep disorders due to disease pain, environmental interference and various medical operations, which seriously affects their efficacy and prognosis. However, this important clinical problem has been neglected for a long time and rarely mentioned and paid attention to. In recent years, with the development and improvement of critical care medicine and the continuous update of sleep monitoring technology and equipment, some clinical studies on sleep disorders and intervention measures in critically ill patients have been reported. Combined with previous research findings and the latest progress, the sleep disorders, harms and current intervention measures of ICU patients are described as follows.

In clinical work, physicians need to make medical decisions at any time, such as determining whether the patient has a certain disease (diagnosis) or the risk of a specific event in the future (prognosis). However, in the clinical diagnosis and treatment process, there are few tools or methods that can accurately predict individuals^[1]。 If we can establish an accurate prediction model of individual patient disease diagnosis, treatment and prognosis, it will bring great convenience to clinical work. A large number of literatures on disease prediction have been published in the past, including the prediction of disease onset, prognosis, diagnosis and treatment^[2,3,4]。 However, many prediction models have inaccurate prediction results^[5]As a result, all kinds of prediction models are in a state of "most established, few validated, and few used" for a long time^[6]。 Forecasting accuracy is the core of forecasting model, which standardizes the generation process of forecasting model^[7]And reporting methods^[8]It not only helps to improve the quality of the prediction model itself, but also helps the reader to quickly understand the prediction model. Individual-specific reporting specification for prognostic or diagnostic multi-factor predictive models (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis, TRIPOD) It is used to standardize the reporting process of multi-factor forecasting models, in order to improve the quality of forecasting model research.

Lung cancer is the most common malignant tumor in the world and the leading cause of malignant tumor death^[1]。 In China, lung cancer is the malignant tumor with the highest morbidity and mortality rate; There were 733,000 new cases and 610,000 deaths in 2015^[2]。

The patient, an 11-year-old and 7-month-old female, went to the endocrinology department of Peking Union Medical College Hospital on November 30, 2017 due to "short stature". The patient was the first child, delivered naturally at full term, and the mother had no history of special drug use during pregnancy. He was 50 cm long at birth and weighed 2.8 kg. Start to talk, walk the same age as the same age children, intellectual development is normal. Since the age of 3, parents found that the patient was shorter than his peers, but he was not treated. Physical examination: height 124.2 cm (3 standard deviations less than the mean height of people of the same age and sex), weight 37 kg, head circumference 54 cm, spread distance of arms 125.9 cm, sitting height 71.3 cm. There is no pigmentation in the skin and mucous membranes throughout the body. There is a black mole on the face, the hairline is not low, there is no neck web, no elbow valgus, and no skeletal deformity is seen. Bilateral breast Tanner stage II, pubic hair Tanner stage II, no clitoral enlargement. The patient's father was 152 cm tall, arms spread 160 cm, and sitting height 86 cm; The mother is 146 cm tall.

A 59-year-old male was admitted to the Department of General Internal Medicine of Peking Union Medical College Hospital on March 31, 2017 due to "fever for 6 days, oliguria and loss of consciousness for 4 days". The patient developed high fever without obvious trigger 6 days ago, with a peak body temperature of 39.5℃, accompanied by chills, obvious fatigue, and a small amount of white phlegm. He took amoxicillin and aminophen and pseudomamethene tablets by himself, and his body temperature control was poor. After 2 days, the urine output was significantly reduced, the urine color became darker, the weakness of both lower limbs was obvious when going out for activities, and the sudden loss of consciousness fell to the ground during going out. The bystander complained that the patient had no convulsions, but shortness of breath and unclear speech after arousal. Routine blood test in emergency department of other hospital showed 12.5×10 white blood cells⁹/L, neutrophil ratio 91.4%, hemoglobin 150 g/L, no abnormality was observed; Blood biochemistry: alanine aminotransferase (ALT) 77 U/L, lactate dehydrogenase 2 971 U/L, creatine kinase (CK) 16 000 U/L, creatine kinase isoenzyme 34.5 μ g/L, creatinine 218 μ mol/L, serum sodium 133 mmol/L, serum potassium 5.3 mmol/L; High sensitivity C-reactive protein (hsCRP)>90 mg/L; Cranial CT: No abnormalities; Chest CT: Increased lobular density in the lower left lung. Consider pulmonary infection, rhabdomyolysis. Moxifloxacin 0.4 g intravenous instillation once/d, piperacillin/sulbactam 2.5 g intravenous instillation once/8 h and hemodialysis treatment were given. The patient's muscle strength has recovered, the peak body temperature has dropped to 38 ℃, the spirit is poor, occasionally delirium, and abdominal pain, nausea and vomiting are denied. Re-examination blood routine: white blood cells 8.15×10⁹/L, neutrophil ratio 86.2%, hemoglobin 91 g/L, balance (-); occult blood in stool (+); Blood biochemistry: ALT 303 U/L, CK 80 018 U/L, creatinine 402 μ mol/L, myoglobin 17 843 μ g/L. Admitted to our hospital for further diagnosis and treatment. The patient had poor sleep at onset, shapeless brown soft stools 1 to 2 times/d, and urine 200 to 300 ml/d in non-dialysis state. Past history: More than 8 years of diabetes history, metformin 0.5 g orally twice/d, blood glucose control was stable. History of hypertension for 8 years, valsartan 80 mg once/d, blood pressure stable at 120-130/70-80 mmHg (1 mmHg =0.133 kPa). Serum creatinine was 108 μ mol/L at 1 month precursor test. Personal history, marriage and childbirth history, and family history are no different.

The patient was a 35-year-old male, married and childless. He was admitted to Qingdao Eighth People's Hospital because of "intermittent swelling and pain of both lower limbs for 14 years, chest tightness and shortness of breath for 4 months". The patient experienced pain and swelling of both lower limbs, low fever, and systemic lymph node enlargement for no reason 14 years ago, and the peripheral blood eosinophils were 1.5×10 in an outside hospital⁹/L, bone marrow cytology examination of hyperplasia and active bone marrow image, eosinophils accounted for 15%, eosinophils late granulocytes, rod-shaped nuclei, lobulated nuclei were the main, and no naive cells were found. Lymph node biopsy showed lymph node granuloma. After 3 months of administration of prednisone 30 mg/d, the swelling and pain of lower limbs were relieved, and the lymph node swelling was relieved. Numbness and pain in the left lower limb appeared 8 years ago. Color Doppler ultrasound of the lower limb artery showed no blood flow in the left dorsal pedis artery and posterior tibial artery. Arteriography: Left lower extremity artery occlusion without blood supply. Peripheral blood eosinophils 5.34×10⁹/L, eosinophil ratio 42%, erythrocyte sedimentation rate (ESR) 131 mm/1 h, C-reactive protein (CRP) 64.12 mg/L, D-dimer 8.3 mg/L. The diagnosis was left lower extremity arterial thrombosis, left foot gangrene, left femoral artery incision, balloon catheter thrombectomy plus balloon dilatation and left lower extremity amputation. Postoperative pathological report: Mixed thrombosis of superficial femoral artery with a few eosinophils in the intima muscle. The wound recovered well after surgery. Extremity edema 5 years ago, hypoalbuminemia, 24 h urine protein quantification of 11 g, clinical diagnosis of nephrotic syndrome, pathological diagnosis of membranous nephropathy stage II by renal biopsy, tubulo-interstitial renal damage, eosinophils 4.24×10⁹/L, eosinophil ratio 35%. Methylprednisolone 40-80 mg/d, intravenous injection of cyclophosphamide twice, 200 mg each time; And treatments such as oral aspirin. Symptoms were stable with prednisone 60 mg once a day and reduced by 5 mg once a day weekly after 3 months. After reducing to 30 mg once a day, reduce by 5 mg every 2 weeks. As well as oral atorvastatin calcium, calcium carbonate, calcitriol, and aspirin, the hormone was gradually reduced, and the course of treatment was 1 year. Urinary protein turned negative. Four months ago, the patient had intermittent chest tightness and shortness of breath, and the condition worsened in the past 3 days, and wheezing could be smelled. Admitted for further diagnosis and treatment.

A 63-year-old male developed neck pain without a clear trigger around April 2017, which gradually worsened. At the beginning of September 2017, a CT examination of the neck in an external hospital showed that the cervical 3~5 vertebral bodies were compressed, and space occupation was considered. Thoracic and abdominal CT and neck MRI examinations were further improved, and multiple bone metastases were considered. It was found that the lower pole of the right kidney occupied space. No contraindications were found, and anterior cervical decompression lesion debridement was performed on September 22, 2017. Postoperative pathology showed metastatic clear cell carcinoma, considering renal origin. Because the patient refused to undergo palliative radiotherapy, he started oral sorafenib (the starting dose was 0.2 g, once/d) in mid-October 2017. After 10 days, it was tolerated well, and the dose was gradually increased to 0.4 g, twice/d, and reduced to 0.2 g, twice/d by the first half month of admission. During the medication, the patient had no obvious neck pain and intermittent diarrhea, which could be improved after symptomatic treatment. After more than 1 month of targeted therapy, renal MRI and cervical CT revealed that the right kidney and bone metastases were basically stable. Two months later, the patient felt neck pain, with a pain score of 3 to 4 points, refused local radiotherapy, and took diclofenac sodium 75 mg intermittently to relieve pain, and the pain was controlled. Two days before admission, the patient found yellow skin and dark yellow urine. Laboratory tests in other hospitals showed that transaminases and bilirubin were significantly increased. The patient was admitted to the Fourth Department of Oncology of our hospital on February 20, 2018 for further diagnosis and treatment. The patient was initially diagnosed as bone metastasis of right renal carcinoma (stage IV). After admission, the coagulation function was examined: prothrombin time 19.1 s, prothrombin time activity 36.3, prothrombin ratio 1.66, international standardized prothrombin ratio 1.66, activated partial thromboplastin time 57.4 s, partial thromboplastin ratio 2.31, fibrinogen content 1.11 g/L; Blood biochemistry: total bilirubin: 195.5 μ mol/L, direct bilirubin: 117.2 μ mol/L, indirect bilirubin: 78.30 μ mol/L, alanine aminotransferase (ALT): 1 640.8 U/L, aspartate aminotransferase (AST): 1 522.5 U/L. There were no abnormalities in blood routine, seven items of virus and all items of hepatitis. Further CT examination showed multiple metastases to sternum, T9 vertebral body and adnexes, L2 vertebral body and sacrum. The lower part of the right kidney occupies space, and it is considered that it is likely to be malignant. The "sleeve sign" can be seen in the hepatic segment of the inferior vena cava and the branch of the portal vein, which is consistent with the changes after liver function is impaired. Comprehensive examination and consultation opinions of gastroenterology department, considering acute drug-induced liver injury and hepatocellular jaundice, magnesium isoglycyrrhizinate, glutathione and other hepatoprotective treatments were given, and sorafenib and diclofenac sodium were stopped. After 1 week, biochemical examination showed that transaminase decreased (ALT: 463.3 U/L; AST: 266.1 U/L), bilirubin gradually increased (total bilirubin: 391.3 μ mol/L), and plasma exchange could not be performed due to abnormal coagulation function. Hepatoprotective treatment was continued for more than 40 days, and transaminase and bilirubin decreased significantly (ALT: 20 U/L; AST: 30 U/L; total bilirubin: 58 μ mol/L) after re-examination.

Pulmonary hypertension (PH) is a progressive disease with poor prognosis, causing increased pulmonary vascular resistance (PVR), increased pulmonary artery pressure, and right ventricular failure, and even death, due to pulmonary vasoconstriction and remodeling. Its pathological features include intimal hyperplasia, media thickening, plexiform lesions and in situ thrombosis, etc. In view of its complex pathophysiology and high mortality, early diagnosis and stratified evaluation of prognosis are extremely important for precise treatment. Biomarkers, because they can be detected in bodily fluids such as blood, urine, or expiratory condensate (EBC), are not only associated with disease severity, clinical progression, and treatment response, but are also easy and convenient, reduce costs, and improve prognosis. Although no ideal biomarker has been found to reveal all the characteristics of PH, human beings have never stopped exploring, and PH biomarkers are described below from the following nine aspects.

Hypertrophic cardiomyopathy (HCM) refers to a genetically heterogeneous myocardial disease characterized by ventricular hypertrophy that is not entirely caused by abnormal cardiac load^[1]。 The prevalence rate is about 0.2%, and more than 1,400 HCM-associated mutations encoding sarcomere-associated proteins have been found in at least 11 genes^[2]。 Left ventricular outflow tract obstruction, mitral regurgitation, ventricular dysfunction, myocardial ischemia and other factors make the clinical manifestations of HCM patients diverse. Patients may have no symptoms or sudden cardiac death. With the continuous improvement of HCM diagnosis and treatment technology and management mode, the current annual sudden death rate of HCM patients is about 0.5%^[3]。 Exercise stress echocardiography (EE) is a kind of imaging technique to evaluate cardiac function by increasing heart rate and cardiac load through physical activity. It reflects the changes of hemodynamics and complex neurohumoral regulation in physiological conditions, and can be safely used for the evaluation of cardiac function in HCM patients under exercise. Identifying patients with dynamic obstruction by evaluating the pressure difference of left ventricular outflow tract is helpful for the selection of treatment plan of septal volume reduction surgery; By evaluating the degree of mitral regurgitation and myocardial mechanics, it is helpful to clarify the cause of symptom changes and cardiac functional reserve; Predicting prognosis of HCM patients by evaluating exercise capacity; By evaluating the changes of heart rate, heart rhythm, blood pressure and other indexes, it is helpful to identify high-risk patients such as autonomic dysfunction and sudden cardiac death. This indicates that EE plays an important role in the clinical management of risk stratification and prognosis analysis of HCM patients^[4]。 Because EE can detect hemodynamic and cardiac function abnormalities that cannot be identified at rest, the 2017 Chinese Adult HCM Diagnosis and Treatment Guidelines further emphasize the importance of EE^[5]。 The application of EE in HCM is described below.

Pancreatic cancer (PC) is a digestive malignant tumor with high degree of malignancy and poor prognosis. Its 5-year survival rate<8%^[1]。 The incidence of pancreatic cancer has been increasing in recent years. When symptoms appear, 85% of patients have developed lymph node or distant metastasis, and more than 80% of pancreatic cancer are in advanced stage when diagnosed and lose the opportunity for surgery^[2]。 In recent years, with the application of new technologies, the research on detecting molecular markers of pancreatic cancer has made continuous breakthroughs at the cellular and molecular levels, which provides a more powerful basis for judging the malignancy of patients' tumors, selecting appropriate adjuvant therapies, and evaluating the prognosis of patients, and has guiding significance for the next treatment of patients. Relevant markers of pancreatic cancer prognosis are reviewed below.