Hypertrophic cardiomyopathy (HCM) is a cardiomyopathy characterized by non-secondary asymmetric hypertrophy of the ventricle, most of which manifests as autosomal dominant inheritance, and it is the main cause of sudden death in young athletes. In recent years, HCM has attracted much attention in epidemiology and molecular mechanism of pathogenicity. This article reviews the epidemiology, pathogenesis and clinical manifestations of HCM.

Objective To investigate the effects of aldosterone on the expression of endothelin(ET)in cultured neonatal rat cardiac fibroblasts(CFs).Methods CFs were isolated by trypsin digestion.ET concentration in conditioned medium was measured by radioimmunoassay,intracellular ET-1 level was evaluated by immunofluorescence assay,and the expression of preproendothelin-1(ppET-1)was detected using reverse transcriptase-polymerase chain reaction(RT-PCR)method.Results Aldosterone(10-9,10-8,10-7 mol/L)induced a dose-dependent changes in ppET-1 mRNA expression,as well as ET-1 synthesis and secretion in CFs.Meanwhile,aldosterone(10-7 mol/L)time-related induced ppET-1 mRNA expression in CFs,which began to increase in 2 h and reached the highest level in 4 h,thereafter decreased.The effects of aldosterone(10-7 mol/L)were significantly inhibited by the pre-incubation with spironolactone(10-6 mol/L).Conclusion Aldosterone increases the expression of ppET-1 mRNA,ET-1 synthesis and secretion via mineralocorticoid receptor.

Objective To evaluate the diagnostic value of cerebrospinal lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation (PNBM) with blood-contaminated cerebrospinal fluid (CSF). Methods A prospective observational study was conducted. 101 patients underwent neurosurgical operation and clinically suspected PNBM admitted to neurosurgical intensive care unit (NSICU) of the First Affiliated Hospital of Sun Yat-sen University from October 2015 to December 2016 were enrolled. Based on red blood cell quantitative test in CSF, the patients were divided into blood-contaminated and non blood-contaminated CSF groups. According to the PNBM diagnostic criteria of 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN), all patients were divided into PNBM group and non-PNBM group. The biochemical indexes levels in CSF were compared among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of CSF lactate for PNBM in blood-contaminated patients.Results A total of 101 suspected PNBM patients were enrolled. In 77 blood-contaminated CSF patients, 39 patients were diagnosed as PNBM (account for 50.6%); in 24 non-blood-contaminated patients, 12 patients were diagnosed as PNBM (account for 50.0%). ① In non-PNBM patients, the lactate level in blood-contaminated CSF was significantly higher than that of non-blood-contaminated CSF (mmol/L: 3.5±1.3 vs. 2.3±1.1,P < 0.01). In PNBM patients, there was no significant difference in lactate level between blood-contaminated CSF and non blood-contaminated CSF (mmol/L: 6.8±2.1 vs. 6.9±2.5,P > 0.05). ② In both blood-contaminated and non blood-contaminated CSF, white blood cell (WBC), protein and lactate levels in PNBM group were significantly higher than those in non-PNBM group [WBC (×106/L): 660.0 (67.5, 1105.0) vs. 41.0 (15.0, 142.5) in blood-contaminated CSF,168.0 (86.5, 269.5) vs. 34.5 (7.0, 83.5) in non-blood-contaminated CSF; protein (mg/L): 4757.8 (2995.2, 10219.8) vs. 1292.8 (924.2, 1936.2) in blood-contaminated CSF, 39247.3 (14900.6, 62552.2) vs. 1441.6 (977.3, 2963.9) in non blood-contaminated CSF; lactate (mmol/L): 6.8±2.1 vs. 3.5±1.3 in blood-contaminated CSF, 6.9±2.5 vs. 2.3±1.1 in non blood-contaminated CSF, allP < 0.05], and glucose and CSF glucose/blood glucose ratio in PNBM group were significantly lower than those in non-PNBM group [glucose (mmol/L): 2.5±1.2 vs. 4.4±1.6 in blood-contaminated CSF, 1.9±1.4 vs. 3.4±0.9 in non blood-contaminated CSF; CSF glucose/blood glucose ratio: 0.28±0.15 vs. 0.46±0.16 in blood-contaminated CSF, 0.24±0.16 vs. 0.45±0.11 in non blood-contaminated CSF, allP < 0.01]. ③ It was shown by ROC curve analysis that CSF lactate level was a good diagnostic parameter for PNBM both in blood-contaminated and non blood-contaminated CSF, and the area under ROC curve (AUC) was 0.91 and 0.97, respectively. When the cutoff value of lactate in non blood-contaminated CSF was 3.35 mmol/L, the sensitivity was 100%, and the specificity was 91.7%. When the cutoff value of lactate in blood-contaminated CSF was 4.15 mmol/L, the sensitivity was 92.3%, and the specificity was 71.1%, and the combination of CSF lactate and glucose achieved better diagnostic specificity (AUC = 0.96, sensitivity was 97.4%, specificity was 84.2%).Conclusions Blood in CSF led to the elevation of CSF lactate as compared with that in non-blood-contaminated CSF of patients with PNBM. CSF lactate was still a good diagnostic parameter for PNBM both in blood-contaminated patients, and the combination of CSF lactate and glucose achieved better diagnostic specificity.

Objective To investigate the dynamic changes in early gastric antrum contraction in patients with craniocerebral injury. Methods The patients with craniocerebral injury admitted to neurosurgery intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from July to November in 2018 were enrolled. The changes in antral contraction frequency (ACF), antral contraction amplitude (ACA) and antral motility index (MI) were dynamically observed at 1-6 days after injury by ultrasonography. According to Glasgow coma score (GCS), the patients were divided into moderate to severe craniocerebral (GCS ≤ 11) and mild craniocerebral injury groups (GCS > 11). The differences in ACF, ACA and MI between the two groups were compared to observe the effect of craniocerebral injury on gastric antral motility. The patients were divided into simple supratentorial and supratentorial combined infratentorial lesion groups according to the lesion location of craniocerebral injury. The differences in ACF, ACA and MI between the two groups were compared to analyze the influence of lesion location on gastric antrum activity. Results A total of 68 patients with craniocerebral injury were screened during the study period, 50 patients were in accorded with the admission criteria, 17 patients were withdrawn from the observation because they could not tolerate the ultrasonography of gastric antrum or discharged from ICU. Finally, 33 patients were enrolled in the analysis. ① The ACF, ACA and MI at 1 day after injury were lower [ACF (times/min): 1.67 (0.00, 2.00), ACA: 42.06 (0.00, 44.45)%, MI: 0.70 (0.00, 0.87)], and then gradually increased, till 6 days after injury, ACF was 1.83 (1.25, 2.79) times/min, ACA was 56.80 (33.25, 60.77)%, and MI was 0.89 (0.50, 1.70), which showed no differences among all time points (all P > 0.05). ② The contractile function of gastric antrum in two groups of patients with different degrees of craniocerebral injury was decreased, especially ACA in patients with moderate to severe craniocerebral injury (n = 22), which showed significant differences at 3 days and 5 days after injury as compared with mild craniocerebral injury [n = 11; 3 days: 35.05 (0.00, 53.69)% vs. 58.51 (49.90, 65.45)%, 5 days: 39.88 (0.00, 77.01)% vs. 56.94 (41.71, 66.66)%, both P < 0.05], indicating that the degree of craniocerebral injury affected the contractive function of gastric antrum. However, there was no significant difference in ACF or MI between the two groups at different time points after injury. ③ The contractile function of gastric antrum was decreased after craniocerebral injury in both groups of patients with different lesion locations of craniocerebral injury. The ACF, ACA, and MI at 3-4 days in patients with supratentorial combined infratentorial lesion (n = 12) were slightly lower than those in patients with simple supratentorial lesion [n = 21; 3 days: ACF (times/min) was 0.83 (0.00, 2.00) vs. 2.25 (0.00, 3.00), ACA was 35.05 (0.00, 53.60)% vs. 49.93 (0.00, 63.44)%, MI was 0.29 (0.00, 1.07) vs. 1.23 (0.00, 1.61); 4 days: ACF (times/min) was 1.42 (0.50, 2.63) vs. 2.00 (1.63, 2.63), ACA was 30.45 (21.69, 60.61)% vs. 43.29 (38.41, 53.35)%, MI was 0.50 (0.15, 1.45) vs. 0.97 (0.66, 1.28)] without statistical differences (all P > 0.05), indicating that the lesion location might not affect the contractive function of gastric antrum. Conclusion In the early stage of craniocerebral injury, the contractile function of gastric antrum was decreased, and the more severe the craniocerebral injury, the worse contractive function of gastric antrum.[Key words] Craniocerebral injury; Antral contraction; Enteral nutrition; Antral ultrasonography

Objective: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. Methods: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol, diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. Results: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. ① The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. ② The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). ③ There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. Conclusions Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. RESULTS: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L. (1) Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01]. (2) When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086). (3) CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of ≥ 10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. CONCLUSIONS It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.
Adult ; Anti-Bacterial Agents/cerebrospinal fluid* ; Drug Monitoring ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/cerebrospinal fluid*

OBJECTIVE: To evaluate trough serum vancomycin concentrations and identify their influencing factors in critically ill neurosurgical patients. METHODS: A retrospective study was conducted. Adult patients who received vancomycin with at least one appropriate monitoring of trough serum vancomycin concentration and admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from November 2017 to July 2019 were enrolled. General information including gender, age, comorbidities, etc., trough serum vancomycin concentrations, vancomycin dosage, duration of vancomycin therapy, urine output, serum creatinine (SCr), concurrent medications (including mannitol,diuretic, vasopressors, non-steroidal anti-inflammatory drugs, polymyxin, aminoglycosides and contrast medium, etc.) were collected for analysis. Trough serum vancomycin concentrations were evaluated and their influencing factors were analyzed by multiple linear regression method. RESULTS: In total, 81 trough serum vancomycin concentration data sets obtained from 28 patients were evaluated. (1) The initial daily dose of vancomycin was 2.00 (2.00, 2.00) g/d. After 4-6 doses, the trough serum vancomycin concentration obtained from initial blood draw was 10.99 (6.98, 16.25) mg/L, of which only 17.9% (5/28) achieving targeted concentrations (15-20 mg/L), 71.4% (20/28) subtherapeutic level and 10.7% (3/28) supratherapeutic level. (2) The duration of vancomycin therapy was 8.0 (6.0, 15.0) days. With average daily dose of 2.00 (1.75, 3.00) g/d, targeted trough vancomycin concentrations were achieved in only 30.9% (25/81) of all cases, subtherapeutic concentrations in 49.4% (40/81) and supratherapeutic concentrations in 19.7% (16/81). (3) There were significant differences in age, comorbidities, vancomycin dosage, diuretics use and mannitol dosage, etc. among different vancomycin concentration groups. Multiple linear regression analysis suggested that the trough serum vancomycin concentration increased by 0.14 mg/L [95% confidence interval (95%CI) was 0.06-0.22] for every 1 year increase in age, increased by 7.22 mg/L (95%CI was 2.08-12.36) in patients with multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease) compared with those without comorbidities, increased by 2.78 mg/L (95%CI was 0.20-5.35) in patients treated with diuretics compared with those without diuretics. The effect of other variables was not statistically significant. It suggested that age, multiple comorbidities (concomitant hypertension, diabetes and coronary heart disease), and diuretic usage affected trough serum vancomycin concentrations. CONCLUSIONS Targeted trough serum vancomycin level is not often achieved in neurosurgical ICU patients following standard dosing. Younger patients are associated with lower trough serum vancomycin concentrations, while diuretic usage, combined with multiple comorbidities are associated with higher trough serum vancomycin concentrations.
Adult ; Anti-Bacterial Agents/blood* ; Critical Illness ; Humans ; Intensive Care Units ; Retrospective Studies ; Vancomycin/blood*

Objective: To evaluate cerebrospinal fluid (CSF) vancomycin concentrations and identify factors influencing CSF vancomycin concentrations in critically ill neurosurgical patients. Methods: A retrospective study was conducted. Adult patients who received vancomycin treatment and CSF vancomycin concentrations monitoring admitted to neurosurgical intensive care unit (ICU) of the First Affiliated Hospital of Sun Yat-sen University from January 2016 to June 2019 were enrolled. General information, vancomycin dosing regimens, CSF vancomycin concentrations, CSF drainage methods and volume of the previous day, and concurrent medications, etc. were collected for analysis. CSF vancomycin concentrations of patients with definite or indefinite central nervous system (CNS) infection, different vancomycin dosing regimens and their influencing factors were analyzed. Results: A total of 22 patients were included. 168 CSF specimens were collected for culture, 20 specimens of which were culture positive, with a positive rate of 11.9%. Sixty cases of CSF vancomycin concentration were obtained. Among the 22 patients, 7 patients (31.8%) were diagnosed with proven CNS infection, 11 patients (50.0%) clinically diagnosed, 2 patients (9.1%) diagnosed with uncertain CNS infection, and 2 patients (9.1%) diagnosed without CNS infection. Intravenous (IV) administration of vancomycin alone was used in 15 cases (25.0%), intrathecal injection in 17 cases (28.3%), IV+intrathecal injection in 23 cases (38.3%), and IV+intraventricular administration in 5 cases (8.3%). The CSF vancomycin concentrations ranged from < 0.24 to > 100 mg/L, with an average level of 14.40 (4.79, 42.34) mg/L.①Administration methods of vancomycin affected CSF vancomycin concentrations. The CSF vancomycin concentration with intrathecal injection or intraventricular administration was higher than that of IV administration alone [mg/L: 25.91 (11.28, 58.17) vs. 2.71 (0.54, 5.33), U = 42.000, P < 0.01].②When vancomycin was administered by IV treatment alone, CSF vancomycin concentrations were low in both groups with definite CNS infection (proven+probable) and indefinite CNS infection (possible+non-infection), the CSF vancomycin concentrations of which were 4.14 (1.40, 6.36) mg/L and 1.27 (0.24, 3.33) mg/L respectively, with no significant difference (U = 11.000, P = 0.086).③CSF vancomycin concentrations rose with the increased dose of vancomycin delivered by intrathecal injection or intraventricular administration. According to the dose of vancomycin administered locally on the day before therapeutic drug monitoring (TDM), cases were divided into the following groups: 0-15 mg group (n = 22), 20-35 mg group (n = 33), and 40-50 mg group (n = 5), the CSF vancomycin concentrations of which were 4.14 (1.09, 8.45), 30.52 (14.31, 59.61) and 59.43 (25.51, 92.45) mg/L respectively, with significant difference (H = 33.399, P < 0.01). Moreover, the cases of CSF vancomycin concentration of≥10 mg/L accounted for 18.2%, 84.8% and 100% of these three groups, respectively. CSF vancomycin concentrations mostly reached target level when dose of vancomycin administered locally were 20 mg/L or more. Conclusions It is difficult to reach target CSF vancomycin concentration for critically ill neurosurgical patients with or without CNS infection by IV treatment. Local administration is an effective treatment regimen to increase CSF vancomycin concentration.