Vitamin D status correlates with the markers of cystic fibrosis-related pulmonary disease.

BACKGROUND: The prevalence of Vitamin D deficiency remains high in cystic fibrosis despite daily supplementation. Vitamin D as an immunomodulator has been related to lower respiratory tract infections in children. The present study was undertaken to examine the association between vitamin D status and markers of cystic fibrosis-related pulmonary disease including exacerbations, bacterial colonization and pulmonary function. METHODS: The study includes review of records of 51 cystic fibrosis patients. Baseline patient variables and serum vitamin D levels were recorded. Based on vitamin D levels study patients were divided into three groups: vitamin-D sufficient (≥20 ng/mL), vitamin-D insufficient (12 to 20 ng/mL), and vitamin D-deficient (≤12 ng/ml). RESULTS: The proportion of children with deficient, insufficient and sufficient vitamin D levels were 47.1%, 15.7%, and 37.2%, respectively. Female sex, bacterial colonization and a greater number of exacerbations were associated with highest odds of developing vitamin D deficiency in patients with CF with 1.77 (0.22-4.61) (p = 0.002), 2.9(0.57-14.82) (p = 0.011), and 5.12 (1.28-20.50) (p = 0.021) respectively. The comparison of vitamin-D levels taken during exacerbations, colonization and during routine follow-up were significant [16.04 (7.42-27.91), 24.3 (15.5-32.4) and 48.54 (18.37-78.7) ng/ml, p < 0.001]. The FEV1 was determined in 24 patients; the comparison was significant between vitamin D-deficient and -sufficient groups [0.75 (0.717-0.777) vs. 0.82 (0.74-0.92) p < 0.05]. CONCLUSION: We concluded that vitamin D deficiency was highly prevalent in children with CF, despite daily supplementation of the vitamin in diet. Further, vitamin D deficiency was associated with a higher rate of pulmonary exacerbations and higher incidence of pulmonary bacterial colonization. In addition, in younger patients, low vitamin D levels were associated with reduced pulmonary function.

Prevalence of Depression among Caregivers of Indian Children with Cystic Fibrosis.

OBJECTIVE: To study the prevalence of depression among caregivers of children with cystic fibrosis and its impact on the health and well being of these children. METHODS: This cross-sectional study was conducted in a tertiary care hospital from September 2015 through August 2016. Forty one parents of children receiving treatment at the Cystic fibrosis (CF) clinic were approached to be part of the study. Six families declined the request resulting in 85% recruitment rate. The Centre for Epidemiological Studies Depression Scale (CES-D) was used to assess depression score among caregivers. The CES-D provides clinical cut-off scores of ≥16 that help in identifying persons at risk for depression. CES-D was completed by the parent closely associated with care of the affected child. Main outcome measure was to find the number of caregivers of patients who has score of ≥16 on CES-D scale, and its effect on growth and respiratory exacerbations of the affected child. RESULTS: A total of 23 fathers and 12 mothers participated in the study. The mean age of male and female caregivers was 30.9 ± 5.4 and 27.8 ± 4.7 y respectively. Eighteen (51.4%) caregivers scored above the clinical cut-off on the CES-D in the index study with mean score of 22.0 ± 4.0. The mean CES-D score among non-depressive caregivers was 7.76 ± 4.2. Significant negative association was found between parental depression and child's health. Children with high parental CES-D score suffered significantly more respiratory exacerbations (3.83 ± 1.2 episodes) in last six months than parents with low CES-D score (2.18 ± 1.28 episodes) (p value = 0.00). Similarly, stunting was more commonly seen in patients with high caregiver CES-D score (15 vs. 7; P value = 0.01). CONCLUSIONS: A very high prevalence of caregiver depression was found in cystic fibrosis, which negatively impacted care and well being of the affected patients. Depression was more common in families with poor economic and education level.

The Diagnostic Dilemma of Traumatic Lumbar Puncture: Current Standing of Cerebrospinal Fluid Leukocyte Corrections and Our Experience With Cerebrospinal Fluid Biomarkers.

OBJECTIVE: To assess the diagnostic efficiency of cerebrospinal fluid markers of procalcitonin, lactate, and cerebrospinal fluid/serum lactate ratio for detecting bacterial meningitis during traumatic lumbar puncture, and to compare these markers with routinely used uncorrected and corrected leukocyte measurements. METHODS: Infants aged ≤90 days with traumatic lumbar puncture were prospectively studied. The diagnostic characteristics of cerebrospinal fluid assays of uncorrected and corrected leukocyte count, procalcitonin, lactate, and lactate ratio were described and compared. RESULTS: Considering the area under the curve (95% CI) analysis and standard cutoff values, the lactate-ratio (0.985 [0.964-0.989] at cutoff 1.2) had the best test indexes for identifying meningitis, followed by lactate (0.964 [0.945-0.984] at cutoff 2.2 mmol/L) and procalcitonin (0.939 [0.891-0.986] at cutoff 0.33 ng/mL) measurement, whereas the corrected total leukocyte count assay (0.906 [0.850-0.962] at cutoff 350 cells/mm3) had diagnostic properties moderately superior to uncorrected total leukocyte count measurement (0.870 [0.798-0.943] at cutoff 430 cells/mm3). CONCLUSION: Cerebrospinal fluid levels of procalcitonin, lactate, and lactate-ratio are reliable markers to diagnose bacterial meningitis in blood-contaminated cerebrospinal fluid.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children / Lactato no líquido cefalorraquidiano: um marcador diferencial para meningite bacteriana e meningite viral em crianças

Abstract Objective: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. Methods: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. Results: At a cut-off value of 3 mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. Conclusions: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3 mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2 mmol/L.

Resumo Objetivo: Estudar o desempenho do lactato no líquido cefalorraquidiano como biomarcador para diferenciar a meningite bacteriana da meningite viral em crianças, e definir uma concentração de lactato ótima no líquido cefalorraquidiano que possa ser significativa para a diferenciação. Métodos: Foram estudadas crianças com achados clínicos compatíveis com meningite. O nível de lactato no líquido cefalorraquidiano e outros parâmetros convencionais do líquido cefalorraquidiano foram registrados. Resultados: Em um valor de corte de 3 mmol/L, o lactato no líquido cefalorraquidiano apresentou uma sensibilidade de 0,90, especificidade de 1,0, valor preditivo positivo de 1,0, valor preditivo negativo de 0,963, com uma precisão de 0,972. Os índices de probabilidade positivo e negativo foram 23,6 e 0,1, respectivamente. Para comparação entre a meningite bacteriana e viral, a área abaixo da curva do lactato no líquido cefalorraquidiano foi 0,979. Conclusões: Concluímos que o lactato no líquido cefalorraquidiano possui alta sensibilidade e especificidade na diferenciação da meningite bacteriana da meningite viral. Embora em um valor de corte de 3 mmol/L o lactato no líquido cefalorraquidiano possua alta precisão de diagnóstico da meningite bacteriana, os níveis médios na meningite viral permanecem basicamente abaixo de 2 mmol/L.

Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children.

OBJECTIVE: To assess the performance of cerebrospinal fluid (CSF) lactate as a biomarker to differentiate bacterial meningitis from viral meningitis in children, and to define an optimal CSF lactate concentration that can be called significant for the differentiation. METHODS: Children with clinical findings compatible with meningitis were studied. CSF lactate and other conventional CSF parameters were recorded. RESULTS: At a cut-off value of 3mmol/L, CSF lactate had a sensitivity of 0.90, specificity of 1.0, positive predictive value of 1.0, and negative predictive value of 0.963, with an accuracy of 0.972. The positive and negative likelihood ratios were 23.6 and 0.1, respectively. When comparing between bacterial and viral meningitis, the area under the curve for CSF lactate was 0.979. CONCLUSIONS: The authors concluded that CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L, CSF lactate has high diagnostic accuracy for bacterial meningitis, mean levels in viral meningitis remain essentially below 2mmol/L.

Flexible Bronchoscopy in Non-resolving Pneumonia.

OBJECTIVE: To study the utility of diagnostic flexible bronchoscopy and bronchoalveolar lavage (BAL) in children with non-resolving pneumonia. METHODS: This was a cross-sectional study conducted in a tertiary care hospital from July 2015 through June 2016. Fifty-two consecutive children of both genders from 1 mo to 14 y of age with a diagnosis of non-resolving pneumonia were included. Flexible bronchoscopy was done in all patients with or without bronchoalveolar lavage (BAL). BAL was sent for gram staining, culture, gene expert™ and lipid laden macrophages examination. Main outcome measures were to find any morphological abnormality in the tracheobronchial tree and organism profile of a positive BAL culture. RESULTS: During the period of 12 mo, 52 consecutive patients of non-resolving pneumonia were enrolled. Median (IQR) age of the study population was 12 (68.8) mo. Mean ± SD duration of illness was 22.7 ± 5.6 d. Flexible bronchoscopy was found to be very safe and effective tool that directly led to definitive diagnosis in 30.7% of cases. It was positive for different organisms in 22 (52.3%) children. Neglected foreign body was seen in five patients. CONCLUSIONS: Non-resolving pneumonia is often an area of clinical dilemma. Bacterial infections are the commonest etiology. Non-infectious causes like tracheobronchomalacia and foreign body aspiration are other important etiologies to be looked for. Early bronchoscopy and bronchoalveolar lavage analysis can play a crucial role in the evaluation of these patients and may provide an important clue or strongly support the specific diagnosis.

Shoshin beriberi-thiamine responsive pulmonary hypertension in exclusively breastfed infants: A study from northern India.

OBJECTIVE: To study the effect of thiamine administration on the resolution of pulmonary hypertension in exclusively breastfed infants. DESIGN: Prospective cohort study. SETTING: Hospital based study of a tertiary care hospital. PATIENTS: A total of 29 infants with 17 males (58.6%) and 12 females (41.4%) were included in the study. INTERVENTION: In addition to the management of shock, right heart failure and renal failure, patients received intravenous thiamine 100mg/kg IV followed by 10mg/day till introduction of supplementary feeds. MAIN OUTCOMES MEASURES: Resolution of shock, metabolic complications and pulmonary hypertension. RESULTS: Mean age at presentation was 78.45±30.7 days. All infants were exclusively breastfed. 86.2% of mothers were on customary dietary restrictions. Biventricular failure and tachycardia was commonly present. There were four deaths in our series. Acute metabolic acidosis was a universal feature with a mean pH of 7.21±0.15. Pulmonary hypertension was present in all patients on admission. Intravenous thiamine 100mg/kg IV stat was given immediately after documenting pulmonary hypertension. Repeat echocardiography showed complete resolution of pulmonary hypertension. CONCLUSION: Many infants present to us with Shoshin beriberi with unusually high pulmonary pressures. These patients respond to thiamine challenge with prompt resolution of metabolic complications and reversal of pulmonary hypertension. We believe this is first of its kind from the region, which is reported.

Blood Pressure-to-Height Ratio as a Screening Tool for Hypertension in Children.

OBJECTIVE: To test whether blood pressure-to-height ratio (BPHR) can be used to screen for hypertension in children. METHODS: Data regarding blood pressure and other variables was recorded for 2702 school children between the ages of 10-16 years as a part of a nutritional survey. RESULTS: The optimal thresholds for defining hypertension in boys were 0.76 for systolic BPHR and 0.50 for diastolic BPHR; the respective threshold in girls were 0.80 and 0.52. CONCLUSION: BPHR can be used as an effective screening test for diagnosing both hypertension and prehypertension in children aged 10-16 years.

Hereditary folate malabsorption with extensive intracranial calcification.

BACKGROUND: Anemia is a common accompaniment of cerebral palsy, mental retardation and neurodegenerative disorders. CLINICAL CHARACTERISTICS: A 4-year-old boy with chronic megaloblastic anemia, global developmental delay, seizures, intracranial calcification and new onset neuro-regression. OBSERVATION: A diagnosis of hereditary folate malabsorption was made, and he was put on oral and injectable folinic acid. OUTCOME: Marked improvement at 6 month follow up. MESSAGE: Hereditary folate malabsorption should be suspected in any child having megaloblastic anemia and neuro degeneration disorder.

Detection of genes for superantigen toxins in methicillin-resistant Staphylococcus aureus clinical isolates in Karachi.

OBJECTIVE: To detect genes for enterotoxins, exfoliative and toxic shock syndrome toxins in Staphylococcus aureus (S. aureus) strains isolated from clinical specimens. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Department of Molecular Genetics, Dr. Ziauddin Hospital, Karachi, from January to December 2010. METHODOLOGY: Two hundred and ninety eight S. aureus clinical isolates were obtained from various clinical samples received at Dr. Ziauddin Hospital, Karachi. Out of these, 115 were detected as methicillin resistant (MRSA) by cefoxitin disk diffusion test showing a prevalence rate of 38.6%. Detection of individual toxin genes was performed by Polymerase Chain Reaction (PCR) by using only one primer pair for each tube. Uniplex primers were preferred as multiplex primers are longer in base pairs and have the potential for cross reaction due to non-specific binding and increase in optimization time. RESULTS: The possession of a single gene or more than a single gene in MRSA isolates was found in 61.73% of clinical samples; the highest number was found in pus swab, followed by sputum, blood, urethral swab, and urine. The prevalence of toxin genes was higher in MRSA as compared to methicillin sensitive (MSSA) isolates (19.12%). CONCLUSION: PCR detects strains possessing toxin genes independent of their expression. The possession of genes for super-antigens seems to be a frequent and habitual trait of S. aureus more so in MRSA.

Clinical and mutation profile of children with cystic fibrosis in Jammu and Kashmir.

OBJECTIVE: To study the clinical and mutation profiles of children with cystic fibrosis in Jammu and Kashmir. METHODS: One hundred consecutive patients presenting with one or more phenotypic features suggestive of cystic fibrosis (CF) were screened by quantitative sweat chloride testing. For patients with positive/equivocal test result on two occasions, CFTR gene mutation analysis was done by polymerase chain reaction. RESULTS: Of the 100 patients, 18 (10 females) were diagnosed to have CF at a median age of 10.5 y (IQR 4.75-15.25 y) while the median age at the onset of symptoms was 12 mo (IQR 4-63 mo) with a delay in diagnosis by 102.4±80.5 months. Clinical features at presentation included failure to thrive (94.4%), chronic cough (78%), recurrent pneumonia (61%), persistent pneumonia (11%), and chronic diarrhea (50%). Positive sweat chloride (>60 meq/L) was seen in 14 (14%) patients and 4 (4%) patients had equivocal (40-60 meq/L) value on two different occasions. Mutational analysis done in 15 patients showed DeltaF508 mutation in 20% (3/15) patients in homozygous form and in 13% (2/15) patients in heterozygous form. Intron 19 mutation 3849+10kb C>T was found in 40% (6/15) in heterozygous form. One (6.6%) patient had DeltaF508 and 3849+10kbC>T mutations in compound heterozygous form. Patients with equivocal sweat chloride and 3849+10kbC>T mutation had delayed onset of pulmonary involvement. CONCLUSION: 3849 +10kbC>T mutation appears to be common in children with cystic fibrosis in Jammu and Kashmir followed by DeltaF508, although the data are quite limited. Although presentation is delayed and sweat chloride is in the equivocal range, severe lung involvement may occur in these patients.

Antiphospholipid syndrome in a neonate.

Antiphospholipid syndrome presenting in the neonatal period is very rare. Although antiphospholipid antibodies from mothers with antiphospholipid syndrome can cross the placenta and put their neonates at risk, the occurrence of thrombotic complications in these neonates is uncommon. We present a 10-day-old neonate who developed Klebsiella sepsis with arterial gangrene of the left lower limb. Investigations revealed thrombosis of the left femoral artery with both the mother and the neonate positive for antiphospholipid antibodies. In conclusion, passive transfer of antiphospholipid antibodies from mothers to their offspring can be associated with significant complication in the presence of secondary risk factors.

Pulmonary thromboembolism as the initial manifestation in a child with antiphospholipid syndrome in the emergency department.

Antiphospholipid syndrome is characterized by recurrent arterial or venous thrombosis at any level of the vascular tree and the presence of circulating antiphospholipid antibodies. The syndrome may be idiopathic or secondary to an underlying autoimmune disorder. The disease is uncommon in children, and manifestations are diverse and underreported. We report the case of a 10-year-old boy who presented with features of pulmonary thromboembolism in the emergency department. Subsequently, he proved to have systemic lupus erythematosus with circulating antiphospholipid antibodies. He had no signs of systemic lupus erythematosus at presentation. In conclusion, antiphospholipid syndrome should also be kept as a possibility in children presenting for the first time with pulmonary thromboembolism in the emergency department.

Magnesium sulfate in severe perinatal asphyxia: a randomized, placebo-controlled trial.

OBJECTIVE: The goal was to study whether postnatal magnesium sulfate infusion could improve neurologic outcomes at discharge for term neonates with severe perinatal asphyxia. METHODS: Forty term (> or =37 weeks of gestation) neonates with severe perinatal asphyxia were studied in a prospective, longitudinal, placebo-controlled trial. Patients were assigned randomly to receive either 3 doses of magnesium sulfate infusion at 250 mg/kg per dose (1 mL/kg per dose) 24 hours apart (treatment group) or 3 doses of normal saline infusion (1 mL/kg per dose) 24 hours apart (placebo group). Both groups also received supportive care according to the unit protocol for perinatal asphyxia. RESULTS: In the treatment group, moderate encephalopathy was present in 35% (7 of 20) of the patients and severe encephalopathy in 65% (13 of 20) of patients at admission. In the placebo group, 40% (8 of 20) of patients had moderate encephalopathy and 60% (12 of 20) of patients had severe encephalopathy. The mean serum magnesium concentration in the treatment group remained at > or =1.2 mmol/L for 72 hours after the first infusion. At discharge, 22% (4 of 18) of infants in the treatment group had neurologic abnormalities, compared with 56% (10 of 18) of infants in the placebo group. Also, neuroimaging (head computed tomography) performed on day 14 yielded abnormal findings for fewer infants in the treatment group than in the placebo group (16% vs 44%). Infants in the treatment group were more likely to be receiving oral feedings (sucking) at discharge than were those in the placebo group (77% vs 37%). Good short-term outcomes at discharge occurred for 77% of the patients in the treatment group, compared with 37% of the patients in the placebo group. CONCLUSION: Postnatal magnesium sulfate treatment improves neurologic outcomes at discharge for term neonates with severe perinatal asphyxia.