Human immunodeficiency virus case detection and antiretroviral therapy enrollment among children below and above 18 months old: A comparative analysis from Cameroon

While pediatric human immunodeficiency virus (HIV) testing has been more focused on children below 18 months through prevention of mother to child transmission of HIV (PMTCT), the yield of this approach remains unclear comparatively to testing children above 18 months through routine provider-initiated testing and counselling (PITC). This study aimed at assessing and comparing the HIV case detection and antiretroviral therapy (ART) enrolment among children below and above 18 months of age in Cameroon. This information is required to guide the investments in HIV testing among children and adolescents.We conducted a cross-sectional study where we invited parents visiting or receiving HIV care in 3 hospitals to have their children tested for HIV. HIV testing was done using polymerase chain reaction (PCR) and antibody rapid tests for children <18 months and those ≥18 months, respectively. We compared HIV case detection and ART initiation between the 2 subgroups of children and this using Chi-square test at 5% significant level.A total of 4079 children aged 6 weeks to 15 years were included in the analysis. Compared with children <18 months, children group ≥18 months was 4-fold higher among those who enrolled in the study (80.3% vs 19.7%, P < .001); 3.5-fold higher among those who tested for HIV (77.6% vs 22.4%, P < .001); 6-fold higher among those who tested HIV+ (85.7% vs 14.3%, P = .24), and 11-fold higher among those who enrolled on ART (91.7% vs 8.3%, P = .02).Our results show that 4 out of 5 children who tested HIV+ and over 90% of ART enrolled cases were children ≥18 months. Thus, while rolling out PCR HIV testing technology for neonates and infants, committing adequate and proportionate resources in antibody rapid testing for older children is a sine quo none condition to achieve an acquired immunodeficiency syndrome (AIDS)-free generation.     

Significant Histologic Changes Are Not Rare in Treatment-naive Hepatitis B Patients with Normal Alanine Aminotransferase Level: A Meta-analysis

Background and AimsChronic hepatitis B is the main cause of liver cancer. However, the most neglected group has been treatment-naive chronic hepatitis B patients with normal alanine aminotransferase (ALT). People have tended to subjectively assume that the liver lesions of these patients are not serious and do not need antiviral treatment. However, the truth is not as optimistic as we thought. We aimed in this study to analyze the proportion of significant inflammation or fibrosis in aforementioned patients.MethodsMedline, Embase, and Cochrane Library were searched up to January 10^th 2020, to identify studies of these patients with liver biopsy. The double arcsine method was used with a random-effect model to combine the proportion of significant inflammation or fibrosis. Potential heterogeneity was explored by subgroup analysis and meta-regression. Outcome of interests included the proportion of significant inflammation or fibrosis and cirrhosis. The secondary outcome was to find the risk factors of significant histological changes.ResultsNineteen eligible studies, with 2,771 participants, were included. The pooled proportion of significant inflammation or fibrosis was 35% [95% confidence interval (CI): 27 to 43] and 30% (95% CI: 25 to 36), respectively. The pooled proportion of cirrhosis was 3% [95% CI: 1 to 5, (12 studies; 1,755 participants)]. In subgroup analysis, old age [vs. young (<40 years-old), 44% vs. 26%, p=0.012] was significantly associated with higher fibrosis stage as well as cirrhosis [vs. young (<40 years-old), 4.8% vs. 1.8%, p<0.001].ConclusionsAbout 1/3 of the treatment-naive chronic hepatitis B patients with normal ALT show significant histological changes, and some even have cirrhosis.     

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population

BackgroundThe current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V?E) to the ramp exercise test in the normal Japanese population are not known.MethodsA total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V?E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V?E versus carbon dioxide (V?CO₂) (V?E vs. V?CO₂ slope), minimum V?E/V?CO₂, and oxygen uptake efficiency slope (OUES) were determined.ResultsFor males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V?E (V?Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V?E vs. V?CO₂ slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V?E/V?CO₂ was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V?Epeak decreased with age and increased with weight and height. The V?E vs. V?CO₂ slope and minimum V?E/V?CO₂ increased with age, while conversely, the OUES decreased with age.ConclusionsWe have established the normal range of VT and V?E responses, the V?E vs. V?CO₂ slope, the minimum V?E/V?CO₂, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.     

Prevalence of advanced liver fibrosis and steatosis in type-2 diabetics with normal transaminases: A prospective cohort study

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)and type-2 diabetes mellitus(T2DM)have an intricate bidirectional relationship.Individuals with T2DM,not only have a higher prevalence of non-alcoholic steatosis,but also carry a higher risk of progression to nonalcoholic steatohepatitis.Experts still differ in their recommendations of screening for NAFLD among patients with T2DM.AIM To study the prevalence of NAFLD and advanced fibrosis among our patient population with T2DM.METHODS During the study period(November 2018 to January 2020),59 adult patients with T2DM and 26 non-diabetic control group individuals were recruited prospectively.Patients with known significant liver disease and alcohol use were excluded.Demographic data and lab parameters were recorded.Liver elastography was performed in all patients.RESULTS In the study group comprised of patients with T2DM and normal alanine aminotransferase levels(mean 17.8±7 U/L),81%had hepatic steatosis as diagnosed by elastography.Advanced hepatic fibrosis(stage F3 or F4)was present in 12%of patients with T2DM as compared to none in the control group.Patients with T2DM also had higher number of individuals with grade 3 steatosis[45.8%vs 11.5%,(P<0.00001)and metabolic syndrome(84.7%vs 11.5%,P<0.00001)].CONCLUSION A significant number of patients with T2DM,despite having normal transaminase levels,have NAFLD,grade 3 steatosis and advanced hepatic fibrosis as measured by liver elastography.     

Mitral valve replacement in children: mortality, morbidity, and haemodynamic status up to medium term follow up

OBJECTIVE—To investigate the outcome of mechanical mitral valve replacement in children after up to 11 years of follow up.
DESIGN—Retrospective analysis of case records. Operative survivors underwent echocardiographic studies to define current haemodynamic status and prosthetic valve function.
SETTING—Tertiary referral centre.
PATIENTS—All 54 children who underwent mitral valve replacement between January 1987 and December 1997.
RESULTS—30 day mortality was 20.3% and was associated with small valve size and supra-annular position. The actuarial freedom from the following events at five years (70% confidence interval (CI)) was: death, including 30 day mortality and transplantation, 68% (70% CI 62% to 75%); bleeding, 89% (70% CI 84% to 94%); non-structural valve dysfunction and reoperation, 92% (70% CI 87% to 97%). The incidence of endocarditis and thromboembolism was low and there was no structural valve failure. Event-free survival was 52% (70% CI 45% to 60%). Low weight, young age, and small valve size increased the chance of death or reoperation. On echocardiography, left ventricular dilatation and wall motion abnormalities were often observed. A high mean gradient over the prosthesis was associated with small valve size but not with length of follow up.
CONCLUSIONS—With the use of mechanical prostheses for mitral valve replacement in children, the problem of structural valve failure is no longer an issue. However, the procedure is still associated with a high complication rate, both at surgery and during follow up, and should therefore be reserved for patients in whom valve repair is not technically feasible.


Keywords: mitral valve replacement; prosthetic mitral valve; child; outcome     

Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry

Background and objectives

Computed tomography (CT) measurements can distinguish between cortical and trabecular bone density in vivo. High-resolution CTs assess both bone volume and density in the same compartment, thus potentially yielding information regarding bone mineralization as well. The relationship between bone histomorphometric parameters of skeletal mineralization and bone density from microcomputed tomography (μCT) measurements of bone cores from patients on dialysis has not been assessed.

Design, setting, participants, & measurements

Bone cores from 68 patients with ESRD (age =13.9±0.5 years old; 50% men) and 14 controls (age =15.3±3.8 years old; 50% men) obtained as part of research protocols between 1983 and 2006 were analyzed by bone histomorphometry and μCT.

Results

Bone histomorphometric diagnoses in the patients were normal to high bone turnover in 76%, adynamic bone in 13%, and osteomalacia in 11%. Bone formation rate did not correlate with any μCT determinations. Bone volume measurements were highly correlated between bone histomorphometry and μCT (bone volume/tissue volume between the two techniques: r=0.70; P<0.001, trabecular thickness and trabecular separation: r=0.71; P<0.001, and r=0.56; P<0.001, respectively). Osteoid accumulation as determined by bone histomorphometry correlated inversely with bone mineral density as assessed by μCT (osteoid thickness: r=−0.32; P=0.01 and osteoid volume: r=−0.28; P=0.05). By multivariable analysis, the combination of bone mineral density and bone volume (as assessed by μCT) along with parathyroid hormone and calcium levels accounted for 38% of the variability in osteoid volume (by histomorphometry).

Conclusions

Measures of bone volume can be accurately assessed with μCT. Bone mineral density is lower in patients with excessive osteoid accumulation and higher in patients with adynamic, well mineralized bone. Thus, bone mineralization may be accurately assessed by μCT of bone biopsy cores. Additional studies are warranted to define the value of high-resolution CT in the prediction of bone mineralization in vivo.     

Prevalence of Monogenic Causes in Pediatric Patients with Nephrolithiasis or Nephrocalcinosis

Background and objectives

Nephrolithiasis is a prevalent condition that affects 10%–15% of adults in their lifetime. It is associated with high morbidity due to colicky pain, the necessity for surgical intervention, and sometimes progression to CKD. In recent years, multiple monogenic causes of nephrolithiasis and nephrocalcinosis have been identified. However, the prevalence of each monogenic gene in a pediatric renal stone cohort has not yet been extensively studied.

Design, setting, participants, & measurements

To determine the percentage of cases that can be explained molecularly by mutations in one of 30 known nephrolithiasis/nephrocalcinosis genes, we conducted a high-throughput exon sequencing analysis in an international cohort of 143 individuals <18 years of age, with nephrolithiasis (n=123) or isolated nephrocalcinosis (n=20). Over 7 months, all eligible individuals at three renal stone clinics in the United States and Europe were approached for study participation.

Results

We detected likely causative mutations in 14 of 30 analyzed genes, leading to a molecular diagnosis in 16.8% (24 of 143) of affected individuals; 12 of the 27 detected mutations were not previously described as disease causing (44.4%). We observed that in our cohort all individuals with infantile manifestation of nephrolithiasis or nephrocalcinosis had causative mutations in recessive rather than dominant monogenic genes. In individuals who manifested later in life, causative mutations in dominant genes were more frequent.

Conclusions

We present the first exclusively pediatric cohort examined for monogenic causes of nephrolithiasis/nephrocalcinosis, and suggest that important therapeutic and preventative measures may result from mutational analysis in individuals with early manifestation of nephrolithiasis or nephrocalcinosis.     

肺癌和癌旁正常肺组织中5种肿瘤标志物比较研究

目的 探讨肺癌组织及癌旁正常肺组织中心钠素、分泌型IgA、铁蛋白、DNA聚合酶、血管内皮生长因子的含量。方法 应用放射免疫法测定39例肺癌和癌旁正常肺组织中心钠素、分泌型IgA、铁蛋白、DNA聚合酶、血管内皮生长因子5种肿瘤标志物含量。结果 5种肿瘤标志物在肺癌组织中的含量均高于癌旁正常肺组织，差异有统计学意义（P均〈0．001）。结论 肺癌细胞具有产生物质的作用。     

Maternal viral load and hepatitis B virus mother‐to‐child transmission risk: A systematic review and meta‐analysis

Aim

The aim of this study was to assess the relationship between maternal viral load and mother‐to‐child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)‐positive mothers.

Methods

PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)‐DNA‐positive and HBV‐DNA‐negative groups. We also examined the dose–response effect of this relationship.

Results

Twenty‐one studies with 10 142 mother–child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV‐DNA‐positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV‐DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random‐effects model. In maternal HBV‐DNA <6 log10 copies/mL, 6–8 log10 copies/mL, and >8 log₁₀ copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198–4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349–13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317–20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose–response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808–4.047) at 6 log10 copies/mL compared with reference (3 log10 copies/mL), and 7.316 (95% CI, 3.268–16.378) at 9 log₁₀ copies/mL. A significant non‐linear dose–response association was also found between maternal viral load and HBV MTCT risk (model χ² = 23.43, P < 0.00001).

Conclusion

Our meta‐analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg‐positive mothers, and maternal viral load was dose‐dependent with HBV MTCT incidence.