Estimating height from arm span measurement in Malawian children

Arm span and standing height were measured in 289 boys and 337 girls aged 6-15 years who were free from physical deformities which can affect stature or arm span. The arm span exceeded height in all age groups of boys and in older girls. At the age of 7, 11 and 12 years girls were significantly taller than the boys and had longer arm span while at the age of 15 years, the trend was opposite. The mean difference between the two anthropometric parameters for boys was 5.45 +/- 4.21 cm (t = 3.556, p < 0.001) and for girls was 4.94 +/- 4.96 cm (t = 3.542, p < 0.001). Correlation coefficient between height and arm span measurements for Malawian boys was 0.983 and for girls was 0.986. Height, arm span and height-arm span difference increased with age of children while height to arm span ratio decreased. The gender difference in height-arm span differences was only significant at the age of 15 years. Multiple regression and cross validation were performed. Height of Malawian children of both sexes can be estimated from equation: Height (cm) = 15.756 + (0.168 x age) + (0.839 x arm span) (SEE = 0.760, R2 = 0.988).     

Respiratory cryptosporidiosis in Malawian children with diarrheal disease

BackgroundRespiratory cryptosporidiosis has been documented in children with diarrhea. We sought to describe the dynamics of respiratory involvement in children hospitalized with gastrointestinal (GI) diarrheal disease.MethodsWe conducted a prospective, observational longitudinal study of Malawian children 2–24 months hospitalized with diarrhea. Nasopharyngeal (NP) swabs, induced sputum and stool specimens were collected. Participants that were positive by Cryptosporidium PCR in any of the three compartments were followed up with fortnightly visits up to 8 weeks post-enrollment.ResultsOf the 162 children recruited, participants had mild-moderate malnutrition (mean HAZ -1.6 (SD 2.1)), 37 (21%) were PCR-positive for Cryptosporidium at enrollment (37 stool, 11 sputum, and 4 NP) and 27 completed the majority of follow-up visits (73%). Cryptosporidium was detected in all compartments over the 4 post-enrollment visits, most commonly in stool (100% at enrollment with mean cycle thresholds (Ct) of 28.8±4.3 to 44% at 8 weeks with Ct 29.9±4.1), followed by sputum (31% at enrollment with mean Ct 31.1±4.4 to 20% at 8 weeks with Ct 35.7±2.6), then NP (11% with mean Ct 33.5±1.0 to 8% with Ct 36.6±0.7). Participants with Cryptosporidium detection in both the respiratory and GI tract over the study period reported respiratory and GI symptoms in 81% and 62% of study visits, respectively, compared to 68% and 27%, respectively, for those with only GI detection, and had longer GI shedding (17.5±6.6 v. 15.9±2.9 days).ConclusionCryptosporidium was detected in both respiratory and GI tracts throughout the 8 weeks post-enrollment. The development of therapeutics for Cryptosporidium in children should target the respiratory as well as GI tract.     

Elevated plasma von Willebrand factor and propeptide levels in Malawian children with malaria

Background

In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls.

Methods and Findings

Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later.

Conclusions

In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.     

Real-time PCR demonstrates Ancylostoma duodenale is a key factor in the etiology of severe anemia and iron deficiency in Malawian pre-school children

Background

Hookworm infections are an important cause of (severe) anemia and iron deficiency in children in the tropics. Type of hookworm species (Ancylostoma duodenale or Necator americanus) and infection load are considered associated with disease burden, although these parameters are rarely assessed due to limitations of currently used diagnostic methods. Using multiplex real-time PCR, we evaluated hookworm species-specific prevalence, infection load and their contribution towards severe anemia and iron deficiency in pre-school children in Malawi.

Methodology and Findings

A. duodenale and N. americanus DNA loads were determined in 830 fecal samples of pre-school children participating in a case control study investigating severe anemia. Using multiplex real-time PCR, hookworm infections were found in 34.1% of the severely anemic cases and in 27.0% of the non-severely anemic controls (p<0.05) whereas a 5.6% hookworm prevalence was detected by microscopy. Prevalence of A. duodenale and N. americanus was 26.1% and 4.9% respectively. Moderate and high load A. duodenale infections were positively associated with severe anemia (adjusted odds ratio: 2.49 (95%CI 1.16–5.33) and 9.04 (95%CI 2.52–32.47) respectively). Iron deficiency (assessed through bone marrow examination) was positively associated with intensity of A. duodenale infection (adjusted odds ratio: 3.63 (95%CI 1.18–11.20); 16.98 (95%CI 3.88–74.35) and 44.91 (95%CI 5.23–385.77) for low, moderate and high load respectively).

Conclusions/Significance

This is the first report assessing the association of hookworm load and species differentiation with severe anemia and bone marrow iron deficiency. By revealing a much higher than expected prevalence of A. duodenale and its significant and load-dependent association with severe anemia and iron deficiency in pre-school children in Malawi, we demonstrated the need for quantitative and species-specific screening of hookworm infections. Multiplex real-time PCR is a powerful diagnostic tool for public health research to combat (severe) anemia and iron deficiency in children living in resource poor settings.     

Pulmonary aspiration in preschool children with cystic fibrosis

Pulmonary aspiration of gastric refluxate (PAGR) has been demonstrated in association with pulmonary inflammation in school aged children with Cystic Fibrosis (CF). We sought to determine if similar findings were present in preschool children. Pepsin was measured in Broncho-alveolar lavage (BAL) fluid collected from clinically stable preschool children with CF and controls. Elevated pepsin levels were found in a subgroup of children with CF, but this was not found to be associated with pulmonary infection, pulmonary inflammation or respiratory or gastrointestinal symptoms.     

Endothelium-based biomarkers are associated with cerebral malaria in Malawian children: a retrospective case-control study

Background

Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM.

Methods and Findings

Plasma samples were tested from children recruited with uncomplicated malaria (UM; n = 32), cerebral malaria with retinopathy (CM-R; n = 38), clinically defined CM without retinopathy (CM-N; n = 29), or non-malaria febrile illness with decreased consciousness (CNS; n = 24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response.

Conclusions

These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.     

The blind nasotracheal aspiration method is not a useful tool for pathogen detection of pneumonia in children

Background

Acute lower respiratory infection (ALRI) is a major cause of hospitalization for children in China, while the etiological diagnosis of ALRI remains a challenge. This study was performed to evaluate the utility of the blind Nasotracheal aspiration (NTA) in the pathogen detection in ALRI through an evaluation of the test''s specificity.

Methodology/Principal Findings

A hospital-based study of children ≤3 years was carried out from March 2006 through March 2007 in Suzhou University Affiliated Children''s Hospital, including 379 cases with ALRI from the respiratory wards, and 394 controls receiving elective surgery. Nasopharyngeal swabs (NPS) and NTA specimens were taken on admission. S. pneumoniae was isolated from 10.3% of NTA samples from ALRI children, H. influenzae from 15.3%, and M. catarrhalis from 4.7%. The false positive rate—the strains from NTA in control group children—was 8.4% (95% CI: 5.8%–11.4%) for S. pneumoniae, 27.2% (95% CI: 22.7–31.5%) for H. influenzae, and 22.1% (95% CI: 18.0%–26.2%) for M. catarrhalis. The agreement between NPS and NTA in the control group was over 70%.

Conclusion/Significance

The blind NTA test is not a useful test for etiologic diagnosis of ALRI.     

Real-time PCR improves Helicobacter pylori detection in patients with peptic ulcer bleeding

Background and Aims

Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies.

Patients and Methods

We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens.

Results

All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%.

Conclusions

Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection.     

Spindle cell neuroendocrine carcinoma of the lung: report of a case with fine needle aspiration cytology and differential diagnostic considerations

BACKGROUND: Spindle cell neuroendocrine carcinomas of the lung may be frequently observed on fine needle cytology (FNC) samples and often pose stimulating differential diagnostic problems. CASE: The cytopathologic findings from FNC performed on a long-standing coin lesion of the lung in a 54-year-old woman were analyzed in view of the data and long clinical history. CONCLUSION: A final diagnosis of low grade spindle cell neuroendocrine carcinoma was reached by combining cytopathologic and immunocytochemical information. The main lesions considered in the differential diagnosis were intrapulmonary inflammatory myofibroblastic tumor (fibrohistiocytic variant) and spindle cell thymoma.     

Up-front mutation detection in circulating tumor DNA by droplet digital PCR has added diagnostic value in lung cancer

Identification of actionable mutations in advanced stage non-squamous non-small-cell lung cancer (NSCLC) patients is recommended by guidelines as it enables treatment with targeted therapies. In current practice, mutations are identified by next-generation sequencing of tumor DNA (tDNA-NGS), which requires tissue biopsies of sufficient quality. Alternatively, circulating tumor DNA (ctDNA) could be used for mutation analysis. This prospective, multicenter study establishes the diagnostic value of ctDNA analysis by droplet digital PCR (ctDNA-ddPCR) in patients with primary lung cancer.CtDNA from 458 primary lung cancer patients was analyzed using a panel of multiplex ddPCRs for EGFR (Ex19Del, G719S, L858R, L861Q and S768I), KRAS G12/G13 and BRAF V600 mutations. For 142 of 175 advanced stage non-squamous NSCLC patients tDNA-NGS results were available to compare to ctDNA-ddPCR. tDNA-NGS identified 98 mutations, of which ctDNA-ddPCR found 53 mutations (54%), including 32 of 45 (71%) targetable driver mutations. In 2 of these 142 patients, a mutation was found by ctDNA-ddPCR only. In 33 advanced stage patients lacking tDNA-NGS results, ctDNA-ddPCR detected 15 additional mutations, of which 7 targetable.Overall, ctDNA-ddPCR detected 70 mutations and tDNA-NGS 98 mutations in 175 advanced NSCLC patients. Using an up-front ctDNA-ddPCR strategy, followed by tDNA-NGS only if ctDNA-ddPCR analysis is negative, increases the number of mutations found from 98 to 115 (17%). At the same time, up-front ctDNA-ddPCR reduces tDNA-NGS analyses by 40%, decreasing the need to perform (additional) biopsies.     

长期鼻饲患者吸入性肺炎抗感染药物治疗及护理干预效果评价

目的探讨对并发吸入性肺炎的长期鼻饲老年患者抗感染药物治疗和加强护理干预的效果。方法将100例长期采取鼻饲饮食的老年患者纳入研究对象,根据数字表的方式随机分为50例的对照组和50例的观察组。对照组患者给予常规护理,观察组患者给予抗感染药物和加强鼻饲饮食的护理干预,并通过适当的口腔护理和心理辅导来降低感染和改善患者不良的心理状态。对比两组患者护理后吸入性肺炎的减少情况,并比较两组患者护理后的心理状态和护理满意度。结果观察组患者给予抗感染药物和加强鼻饲饮食的护理干预,吸入性肺炎(10.00%)、腹泻(8.00%)和便秘的发生率(4.00%)明显低于对照组(38.00%,34.00%,30.00%);SAS评分(32.33±8.09)分和SDS评分(31.46±7.87)分明显低于对照组(48.57±12.15)分和(49.28±12.32)分;护理总满意度(98.00%)明显高于对照组(72.00%),组间比较差异有统计学意义(P0.05)。结论对长期鼻饲老年患者给予合理的抗感染药物和有效的护理干预,可以减少吸入性肺炎的并发情况,改善患者不良情绪,患者对护理的满意度也相应提高。     

老年吸入性肺炎患者病原菌感染特点及相关危险因素分析

目的分析老年吸入性肺炎患者病原菌感染特点及其相关危险因素,为临床有效防治老年吸入性肺炎提供依据。方法纳入2013年1月-2015年12月期间本院收治的需行机械通气治疗的老年患者120例,根据治疗过程中患者是否发生吸入性肺炎分为吸入性肺炎组(47例)和无吸入性肺炎组(73例)。分析吸入性肺炎组患者的病原菌分布情况及构成比;单因素分析吸入性肺炎的可能相关因素在两组间的差异,对单因素分析中存在显著差异的因素进行多元Logistic回归分析。结果 (1)47例吸入性肺炎患者中共检出病原菌96株,其中革兰阴性菌65株(67.7%)、革兰阳性菌20株(20.8%)、真菌11株(11.5%)。(2)单因素分析结果显示,两组间年龄、咳嗽反射障碍、意识障碍、长期卧床、吞咽障碍、胃食管反流、鼻饲饮食、低白蛋白血症、高血压、糖尿病、冠心病、口腔疾病等因素存在明显差异(P0.05)。(3)多元Logistic回归分析结果显示,年龄≥70岁、咳嗽反射障碍、意识障碍、长期卧床、吞咽障碍、胃食管反流、鼻饲饮食、低白蛋白血症、高血压、冠心病均是吸入性肺炎的危险因素(P0.05)。结论老年吸入性肺炎感染的病原菌主要以革兰阴性菌为主;年龄≥70岁、存在咳嗽反射障碍、意识障碍、长期卧床、吞咽障碍、胃食管反流、鼻饲饮食以及合并低白蛋白血症、高血压、冠心病等基础病的老年患者更易发生吸入性肺炎。     

Zenker's diverticulum as a cause of aspiration pneumonia and dysphagia in nonagenarian with moderate dementia

The association between aspiration pneumonias and digestive symptoms is frequent in geriatric patients and is usually attributed to comorbidity, being the most frequent causes cerebrovascular disease or dementia. We present the case of a 90-year-old woman, with malnutrition associated with progressive dysphagia and episodes of aspiration pneumonia, due to Zenker's diverticulum, which was treated surgically. We provide a review of this disease and analyze the criteria that can be applied when considering surgical indication in the oldest-old with dementia.     

Streptococcus pneumoniae serotypes in children with acute pneumonia and pleurisy

The study of pneumococci of different serotypes, isolated from patients with acute pneumonia and pleuritis and from healthy children was carried out. Among the pneumococcal serotypes causing pneumonia and pleuritis in children serotypes 1, 6, 19, 14 and 3 were most widely spread and constituted 62.3% of all isolated pneumococci. In young children cases of acute pneumonia and pleuritis were more often induced by serotypes 6 and 14 and in older children, by serotypes 1 and 3. In patients with uncomplicated pneumonia and pleuritis differences in the detected serotypes of pneumococci were observed, and the disease course differed in severity. Serotypes 14, 3 and 3 induced destructive processes in the lungs more often than other serotypes. Monitoring of the sensitivity of pneumococci to antibiotics showed that most of the strains retained high sensitivity to penicillin and ampicillin. In most cases the detected resistant pneumococcal strains belonged to serogroup 19.     

肺炎支原体肺炎患儿口咽部菌群的改变

目的 比较健康儿童与肺炎支原体肺炎患儿口咽部菌群的差异,分析肺炎支原体感染对儿童口咽部菌群变化的可能影响。方法 采用高通量测序技术,对30例肺炎支原体肺炎患儿及30例健康儿童16S rDNA进行测序分析,比较两组间的菌群多样性及在门、属水平上菌群结构差异。结果 健康儿童与肺炎支原体肺炎患儿在性别、年龄、抗生素使用等方面差异无统计学意义。肺炎支原体肺炎患儿口咽部菌群多样性比健康儿童明显降低。在门水平上,Proteobacteria（变形菌门）、Bacteroidetes（拟杆菌门）和Fusobacteria（梭杆菌门）在健康儿童中相对丰度显著高于肺炎支原体肺炎患儿组,而Firmicutes（厚壁菌门）、Tenericutes（柔膜菌门）和Actinobacteria（放线菌门）在肺炎支原体肺炎患儿组中相对丰度均显著高于健康儿童组;在属水平上,两组排在相对丰度前10位的属差异具有统计学意义,共有6个属在肺炎支原体肺炎患儿中显著增加,分别为Staphylococcus（葡萄球菌）、Actinomyces（放线菌属）、Acinetobacter（不动细菌属）、Atopobium（阿托波菌属）、Corynebacterium（棒状杆菌）和Abiotrophia（营养缺陷菌属）。结论 肺炎支原体肺炎患儿口咽部菌群存在明显的改变,其口咽部菌群多样性比健康儿童明显降低,在门、属水平肺炎支原体肺炎患儿与健康儿童差异均有统计学意义。