[Comparison of the predictive value of Padua and the IMPEDE assessment scores for venous thromboembolism in patients with newly diagnosed multiple myeloma: A single institution experience].

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.

[Clinical characteristics of bone disease in multiple myeloma and clinical significance of monitoring bone metabolic markers].

OBJECTIVE: To observe the clinical characteristics of bone disease in patients with multiple myeloma (MM) and the clinical significance of monitoring bone metabolic markers. METHODS: The data of 178 MM cases newly diagnosed in Beijing Ji Shui Tan Hospital from January 2009 to June 2014 were reviewed to analysis the types and classification of bone disease and to observe the clinical characteristics of patients with different grades of bone disease. The levels of bone metabolic markers total procollagen type Ⅰ N-terminal peptide (tPINP) and ß C-terminal telopeptide of type Ⅰ collagen (ß-CTX) were monitored regularly in the two years following treatment in 66 cases. RESULTS: (1) Among the 178 newly diagnosed MM cases, 167 cases complained of pain in bones on first visit, 35 cases combined with hypercalcemia, 83 cases combined with osteoporosis, 154 cases combined with osteolytic bone destruction, and 73 cases combined with pathologic fracture. The most common osteolytic location was the spine. The most common fracture sites was the spine. (2) According to bone disease grading, the 178 cases were divided into group A (bone grade 0-2, n=51) and group B(bone grade 3-4, n=127). There were no significant differences between group A and group B in gender, median age, therapeutic effect/ineffec, median overall survival, median progress-free survival, mean serum lactic dehydrogenase, mean albumin, urine light chains and serum creatinine(all P>0.05). Compared with group A, group B had lower hemoglobin level[(99.78±29.93)vs (108.84±29.30) g/L], and higher blood calcium level[(2.47±0.40)vs (2.30±0.29) mmol/L], serum ß2-microglobuin level[(6.04±4.84)vs (4.12±3.97)mg/L], and bone marrow plasma cells percentage(33.30%±24.87% vs 23.51%±22.67%)(all P<0.05). (3) Before treatment, the levels of ß-CTX and tPINP in patients of group B(n=47) were higher than those in group A(n=19)(median 0.78 vs 0.42 µg/L, 60.95 vs 43.47 µg/L, both P<0.05). The ratio of ß-CTX /tPINP in group B was higher than that in group A (median 0.017 vs 0.012, P<0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both group A and group B (both P>0.05), the level of ß-CTX decreased significantly compared with that before treatment in both groups(median 0.16 vs 0.42 µg/L, 0.26 vs 0.78 µg/L, both P<0.05); the ratio of ß-CTX /tPINP decreased significantly compared with that before treatment in both group A and in group B(median 0.008 vs 0.012, 0.011 vs 0.017, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that after 3 months in both group A and group B (all P>0.05). (4)All patients were divided into two groups according to the therapeutic effect: effective group included patients who reach the effect of partial remission or better remission(n=48), while ineffective group included patients who did not reach the effect of partial remission(n=18). Before treatment there were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio between the effective groupand the ineffective group (all P>0.05). After chemotherapy for 3 months, there were no differences in the level of tPINP compared with that before treatment in both effective group and ineffective group (all P>0.05), but the level of ß-CTX decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.24 vs 0.60 µg/L, 0.44 vs 0.95 µg/L, both P<0.05). The ratio of ß-CTX /tPINP decreased significantly compared with that before treatment both in effective group and ineffective group (median 0.005 vs 0.012, 0.005 vs 0.011, both P<0.05). There were no differences in the level of ß-CTX, tPINP and ß-CTX/tPINP ratio after treatment for 6 months, 1 year and 2 years compared with that for 3 months both in effective group and ineffective group (all P>0.05). CONCLUSIONS: Pain in bones, osteolysis and pathological fracture are the most common clinical manifestations in myeloma-related bone disease. The severity of bone disease can reflect the tumor load, but may not affect the therapeutic effect and the overall survival. The bone metabolic markers tPINP and ß-CTX can be used to evaluate the severity of myeloma-related bone disease at diagnosis and to monitor the effect of treatment for bone disease.

The lipid profile in obese asthmatic children compared to non-obese asthmatic children.

BACKGROUND: A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment. MATERIALS AND METHODS: One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9kg/m(2), n=30); Group II under-weight (BMI<20kg/m(2), n=30); Group III overweight (BMI=25-30kg/m(2), n=25); and Group IV obese (BMI>30kg/m(2), n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides. RESULTS: There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups. CONCLUSION: Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma.

Serum Irisin Level is Higher and Related with Insulin in Acanthosis Nigricans-related Obesity.

OBJECTIVE: Acanthosis nigricans (AN) is proved to be a skin phenotype of hyperinsulinemia especially in obese patients. Irisin is a new myokine which plays an important role in metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes. The role of irisin in the development of AN-related obesity is not yet understood. In this study, we aimed to investigate the relationship between irisin and AN-related obesity. Patients & Measurements: 30 obese patients without AN (OB group), 30 obese patients with AN (AN group), and 20 age-matched healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral Glucose Tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured at 0, 30, 60,120 and 180 min. The AUC (area under curve) of glucose and insulin was calculated. Serum irisin was measured by ELISA. RESULTS: Hyperinsulinemia is found in both AN and OB groups. The AN group had higher levels of insulin but better blood glucose tolerance and insulin response. The difference in irisin levels between the 3 groups was statistically significant, with the AN group showing the highest serum level of irisin. Serum irisin levels were positively correlated with BMI, and fasting insulin. CONCLUSION: AN is a state of hyperinsulinmia and has better insulin response and glucose tolerance compared to obese patients without AN. Serum irisin may be a protective factor against impaired beta cell function in obesity with AN.

Sustained outcomes of a peer-taught family education program on mental illness.

OBJECTIVE: This study examines 6-month follow-up data from participants in a randomized trial of a peer-driven 12-session family support and education program, called family-to-family (FTF) and offered by the US National Alliance on Mental Illness, to determine whether improvements in distress, family functioning, coping and empowerment were sustained. METHOD: Individuals randomized to the FTF condition were assessed after program completion and then 3 months later on measures of distress, family functioning, coping, and empowerment. We used a multilevel regression model (sas proc mixed) to test for significant changes over time (baseline, 3 and 9 months). RESULTS: All significant benefits that FTF participants gained between baseline and immediately post-FTF were sustained at 9 months including reduced anxiety, improved family problem-solving, increased positive coping, and increased knowledge. Greater class attendance was associated with larger increases in empowerment and reductions in depression and displeasure with ill relative. CONCLUSION: Evidence suggests that benefits of the FTF program were sustained for at least 6 months without any additional boosters or supports. Peer-based programs may produce sustained benefits for individuals seeking help in addressing challenges and stresses related to having a family member with a mental illness.

Modeling Caco-2 permeability of drugs using immobilized artificial membrane chromatography and physicochemical descriptors.

This study evaluates the potential of immobilized artificial membrane (IAM) chromatography, in combination with other physicochemical descriptors for high-throughput absorption profiling during lead optimization. An IAM chromatographic method was developed and validated. Absorption profiles of 32 structurally diverse compounds (acidic, basic, neutral and amphoteric) were then evaluated based on their IAM retention factor (log k'IAM), molecular weight (MW), calculated log P (C log P), polar surface area (PSA), hydrogen bonding capacity (HBD and HBA) and calculated Caco-2 permeability (QPCaco). Using regression and stepwise regression analysis, experimental Caco-2 permeability was correlated against log k'IAM and a combination of various physicochemical variables for quantitative structural-permeability relationship (QSPR) study. For the 32 structurally diverse compounds, log k'IAM correlated poorly with Caco-2 permeability values (R2 = 0.227). Stepwise regression analysis confirmed that Clog, PSA, HBD and HBA parameters are not statistically significant and can be eliminated. Correlation between Caco-2 cell uptake and log k'IAM was enhanced when molecular size factor (MW) was included (R2 = 0.555). The exclusion of 11 compounds (paracellularly and actively transported, Pgp substrates and blocker, and molecules with MW lesser than 200 and greater than 800) improved the correlation between Caco-2 permeability, IAM and MW factors to R2 value of 0.84. The results showed that IAM chromatography can only profile the passive absorption of drug molecules. Finally, it was confirmed in this study that the IAM model can accurately identify the Caco-2 permeability of nontransported Pgp substrates, such as verapamil and ketoconazole, through passive permeation because of their high permeability. IAM chromatography, combined with molecular size factor (MW), is useful for elucidating biopartitioning mechanism of drugs.

Identification and characterization of four novel large deletions in the human neurofibromatosis type 1 (NF1) gene.

We studied 20 unrelated NF1 patients by Southern blots with seven cDNA probes and loss of heterozygosity (LOH) analysis with four intragenic microsatellites (IVS26-2.3, IVS27AC28.4, IVS27AC33.1, and IVS38GT53.0). Four novel large deletions (178, 184, 236, and 237) have been identified and characterized. The breakpoint of deletion 178 was located in between exons 23-2 and 27b and the sequences downstream of the breakpoint were deleted. For deletion 184, the breakpoint was in between exons 27b and 29, and the region upstream of the breakpoint was deleted. With deletion 236, the breakpoint was in between exons 14 and 18 and the region downstream of the breakpoint was deleted. The breakpoint of deletion 237 was in between exons 38 and 45 and the sequences upstream of the breakpoint were deleted. These deletions were distributed randomly across the NF1 gene and no deletion hot spot was found. Our study suggests that the combination of analyses of loss of heterozygosity, southern blotting and southern blot densitometry can be used as a powerful method to detect large deletions, especially when family record is not available or the patient is a sporadic case.

A novel mutation in the neurofibromatosis type 1 (NF1) gene promotes skipping of two exons by preventing exon definition.

Using a protein truncation assay, we have identified a new mutation in the neurofibromatosis type 1 (NF1) gene that causes a severe defect in NF1 pre-mRNA splicing. The mutation, which consists of a G to A transition at position +1 of the 5' splice site of exon 12a, is associated with the loss of both exons 11 and 12a in the NF1 mRNA. Through the use of in vivo and in vitro splicing assays, we show that the mutation inactivates the 5' splice site of exon 12a, and prevents the definition of exon 12a, a process that is normally required to stimulate the weak 3' splice site of exon 12a. Because the 5' splice site mutation weakens the interaction of splicing factors with the 3' splice site of exon 12a, we propose that exon 11/exon 12a splicing is also compromised, leading to the exclusion of both exons 11 and 12a. Our results provide in vivo support for the importance of the exon definition model during NF1 splicing, and suggest that the NF1 region containing exons 11 and 12a plays an important role in the activity of neurofibromin.

Identification of malnutrition in children with cerebral palsy: poor performance of weight-for-height centiles.

This study aims to evaluate the use of the United States National Center for Health Statistics (NCHS) weight-for-height centiles (WHC) in screening children with cerebral palsy (CP) for depleted body fat and to identify an alternate screening method. Growth data from 276 children aged from 3 to 12 years with CP were analyzed retrospectively. Height or a proxy for height, mid-upper arm circumference, weight, and skinfold thicknesses were recorded. Mid-upper arm fat area was calculated for each participant. The sensitivities and specificities of WHC and a number of alternative anthropometric screening methods for identifying participants with severely depleted fat stores were determined. WHC <10th centile failed to identify 45% of children with severely depleted fat stores. Triceps skinfold thickness <10th centile identified 96% of malnourished children. WHC standards lack adequate sensitivity for identification of severely depleted fat stores in children with CP. Use of triceps skinfold thickness, using cut-off value of <10th centile for age and sex, is recommended to screen for suboptimal fat stores in children with CP.

Factors predisposing infants to lower respiratory infection with wheezing in the first two years of life.

BACKGROUND: Acute lower respiratory illness (LRI) early in life has been implicated as a factor for adverse respiratory outcomes later in life. Factors that predispose infants to LRI with wheezing have not been conclusively defined. OBJECTIVES: This prospective study assessed factors that might contribute to LRI with wheezing in the first 2 years of life. METHODS: Seventy-one healthy full-term infants (44 boys, 27 girls) completed the 2-year follow-up. Demographic and environmental factors were evaluated by questionnaire. Respiratory function was assessed by single occlusion technique and rapid thoracic compression technique. Both techniques were performed successfully in 40 infants at 2.6 (+/- 1.4) months old before they developed any episode of LRI. RESULTS: Eighteen infants (25%) developed LRI with wheezing. The first episode of LRI with wheezing occurred in the first year of life in 8 infants, and in the second year of life in 10 infants. There were no significant differences in the demographic or environmental features between infants with or without wheezing LRI, or between infants who acquired LRI with wheezing in the second year of life and those who did not acquire or acquired in the first year of life. Infants from different groups did not differ in airway resistance or maximal flow at functional residual capacity. Infants who developed LRI with wheezing had higher incidence of low values for total respiratory system compliance corrected for body weight compared with those who did not (5/30 versus 6/10, odds ratio = 7.5, 95% confidence interval: 1.53 to 36.7, P = .013). None of the variables of the pulmonary function test could differentiate infants who subsequently developed LRI with wheezing in the first year of life or did not develop any episode of LRI with wheezing from those who developed LRI with wheezing in the second year of life. CONCLUSIONS: Differences in lung function in early life may predispose infants to LRI with wheezing in the first 2 years of life.

A novel and very peculiar HincII polymorphism in the 5' region of the human neurofibromatosis type 1 (NF1) gene.

We report a HincII polymorphism in the 5' end of the neurofibromatosis type 1 gene (NF1) as detected with a probe made of exons 1 to 4a (nucleotides 2 to 401 of the cDNA). This HincII site is most probably in an intron. Evidence presented suggests the probe reveals not one but two similar polymorphisms.

In situ hybridization of hepatitis B DNA in hepatitis B-associated glomerulonephritis.

Renal tissues from 43 of 49 children with hepatitis B virus-associated glomerulonephritis (HBV-GN) were examined for HBV DNA by in situ hybridization (ISH) assay within the last 10 years. HBV DNA was identified in 41 of the 43 cases (95.3%). HBV DNA was distributed generally in the nucleus and cytoplasm of epithelial cells and mesangial cells of glomeruli, and epithelial cells of renal tubules. HBV DNA also existed simultaneously in renal interstitial tissues in some of these cases. The positive results from HBV DNA ISH correlated well with HBV antigen assays. The analyses implied that the more extensive the existence of HBV DNA in the nephron unit and interstitial tissue, the more severe the clinical manifestation. The duration of proteinuria in cases with HBV DNA in renal tubules was much longer than in those with no HBV DNA in renal tubules. The persistence of the HBV genome or genes in the kidney could lead to the expression of viral antigens in renal tissues and might cause cellular pathological alteration. This would support utilization of antiviral therapy, such as cytokines, in the treatment of HBV-GN.

Labor pain before elective cesarean section reduces neonatal respiratory distress.

Neonatal respiratory distress is a major complication of elective Cesarean section. To clarify the effect of preceding labor on the incidence of respiratory distress, we studied 45 term neonates who were born with labor and 85 term neonates who were born without labor. Transient tachypnea of the newborns accounted for the majority of respiratory distress in term neonates. Respiratory distress occurred less frequently in term neonates delivered after the onset of labor compared to those delivered before the onset of labor (11.1% vs. 31.8%, p < 0.002). Neonatal respiratory distress syndrome (RDS) occurred in 4 of 85 (4.7%) term neonates delivered before the onset of labor. In contrast, none of the 45 term neonates born after the onset of labor developed RDS (p = 0.02). Awaiting the onset of labor appears to be beneficial in preventing neonatal RDS for term neonates delivered by elective Cesarean section.

Lung mechanics in infants with left-to-right shunt congenital heart disease.

To clarify which hemodynamic measurement correlates best with lung mechanics in infants with congenital heart disease and left-to-right shunts, dynamic pulmonary function tests and echocardiography were performed in 26 infants with such disease (study infants) and in 37 normal, healthy infants (control infants). The tidal volume and pulmonary compliance (CL) were lower and airway resistance higher in infants with congenital heart disease than in control infants. A significant correlation was demonstrated between CL, expiratory resistance (Re), and the right pulmonary artery-to-aortic size ratio (RPA/DAO). CL and Re also correlated well with the corrected acceleration time square root of RR ratio (ACT/square root of RR: ACT, acceleration time and RR: length of the cardiac cycle) of pulmonary flow velocity. Stepwise multiple regression analysis revealed that RPA/DAO correlated best with both CL and Re. It is concluded that infants with congenital heart disease and left-to-right shunts have lower lung compliance and higher expiratory airway resistance than normal children, and that RPA/DAO is the echocardiographic parameter that correlates best with the changes in lung mechanics.

Pulmonary mechanics and the energetics of breathing in healthy infants.

In order to understand the change in the pulmonary mechanics and energetics of breathing in infants, dynamic pulmonary function tests were studied on 84 occasions in 70 normal healthy infants between birth and seven months of age. All of the study infants were born at full-term and had no lower respiratory infections after birth. Airflow and transpulmonary pressure were measured simultaneously and utilized to calculate values of pulmonary mechanics and energetics of breathing. Variables of ventilation (respiratory frequency, tidal volume, minute ventilation, and inspiratory time) had good correlation with age. Lung compliance increased with age. However, when it was expressed in body weight the lung compliance was independent of age (1.34 +/- 0.37 mL/cmH2O/kg for infants studied). Pulmonary resistance did not differ statistically between different age-groups and it correlated with the level of lung compliance (r = 0.3411, p < 0.01). Older infants had a higher flow rate and esophageal pressure change. This might imply that the older the infant is, the more forceful the breath becomes. The work of breathing was higher in infants of older age and in infants with higher inspiratory pulmonary resistance or lower lung compliance (r = 0.6257, 0.3825 and 0.4579, respectively; p < 0.05). This study establishes reference values for the pulmonary mechanics and energetics of breathing in infancy which may be of assistance in the objective evaluation of respiratory status in infants.

Concentrations of serum insulin-like growth factor-I (IGF-I) in normal Chinese children and children with growth hormone deficiency.

In order to establish the range of the serum insulin-like growth factor-I (IGF-I) concentrations for various ages in normal Chinese children and to evaluate the use of IGF-I levels in the diagnosis of classical growth hormone deficiency, the serum concentrations of IGF-I of 310 normal Chinese children (137 boys and 173 girls) and 13 children (10 boys and three girls) with classical growth hormone deficiency were determined. In this study, we divided normal subjects of each sex into five age groups. In both sexes, an increase in the mean IGF-I levels of normal children was statistically significant around the age of three and at the age corresponding to the onset of puberty. The mean IGF-I levels in the serum of girls were higher than those in boys at all ages. However, the differences were statistically significant only at 8-10 and 10-12 years of age. The serum IGF-I concentrations of 13 patients with classical growth hormone deficiency ranged from undetectable to 78 ng/mL, and all of their IGF-I levels were lower than the normal range for their age. Because of the low IGF-I concentrations in the serum of normal children younger than three years of age, its clinical application in this age group is limited. From this study, we conclude that the determination of serum IGF-I concentrations is of clinical value in the diagnosis of growth hormone deficiency in Chinese children over three years of age.

PIP: A group of 310 normal, healthy Chinese children (137 boys and 173 girls) ranging in age from 5 days to 12 days were selected from the nursery, well-baby clinic, kindergarten. and primary school. The patients with classical growth hormone deficiency consisted of 13 children (10 boys and 3 girls) between the ages of 6 and 12 years. 2 patients had been operated on for craniopharyngioma, and 11 children had idiopathic hypopituitarism. The determination of serum insulin-like growth-I (IGF-I) levels was done when they were euthyroid. The mean serum IGF-I levels in both males and females aged below 3 years were significantly lower than those of any other age group. The next significant increment in serum IGF-I levels ocurred at 8-10 years in females and 10-12 years in males. The mean serum IGF-I concentration in girls aged 6-8 years or younger and boys aged 8-10 years or younger were significantly lower than those in normal adult females or males. Also, the mean IGF-I levels in the serum of girls were higher than those in boys in all age groups; however, the differences were statistically significant only at 8-10 years and 10-12 years of age. All of the 13 children with classical growth hormone deficiency had serum IGF-I levels lower than the range for their sex- and age-matched peers, but the serum IGF-I concentrations did not change with age. The serum IGF-I levels in children under 3 years were only about one-third of the adult values, and there was a significant rise in the serum IGF-I concentrations after 3 years of age in both sexes. The mean serum IGF-I levels in the different age groups did not reach adult levels until around 10 years of age. Serum IGF-I levels in normal adults cannot be used as a reference for diagnostic comparison of serum IGF-I levels in prepubertal children; however, the determination of the serum IGF-I concentration is of value in the diagnosis of growth hormone deficiency in Chinese children.

Peritonitis in children with nephrotic syndrome.

In a retrospective review of 300 children with nephrotic syndrome seen at National Taiwan University Hospital throughout the 12-year period from 1978 to 1990, 20 episodes of peritonitis were identified in 17 patients (7.4%). Gram-negative bacilli (E. coli and Klebsiella pneumoniae) were the majority of pathogens, accounting for 55% of all the cases. Streptococcus pneumoniae were cultured from only 15% of the patients. An additional 15% had negative culture results, but were clinically responsive to penicillin. In 15% of cases the cause was unknown. Clinically, peritonitis was characterized by abdominal pain (100%), abdominal tenderness (100%), rebounding pain (85%), leukocytosis (85%), and fever (75%). Based on this data, it seems reasonable to initiate antimicrobial therapy in nephrotic children with suspected peritonitis, using a combination of penicillin plus either an aminoglycoside or a broad-spectrum cephalosporin. This regimen should be continued until culture results are available.