Comparison of humoral immune response in heterologous and homologous COVID-19 booster vaccine groups using CoronaVac and mRNA-based BNT162b2 vaccines.

BACKGROUND: Heterologous COVID-19 booster vaccination is an alternative strategy to homologous vaccination, especially in developing countries, due to shortages, delays, or unequal distribution of COVID-19 vaccines. We compared cohorts vaccinated with different vaccine combinations to investigate whether a heterologous booster dose of mRNA-based BNT162b2 vaccine boosts the immune response in individuals primed with the CoronaVac vaccine. METHODS: Anti-RBD IgG is generally measured 4 weeks after primary immunization and 4 weeks after booster vaccination. Data on anti-receptor-binding domain (anti-RBD) IgG antibody titers and clinical characteristics were provided by infection control units. RESULTS: The highest median anti-RBD IgG antibody titers (14589 AU/mL) after primary immunization was observed in the group vaccinated with two doses of BNT162b2 vaccine. Antibody titers were lower 4 months or more after the second CoronaVac vaccine dose in CoronaVac recipients with or without previous COVID-19. In the homologous COVID-19 booster vaccine group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of CoronaVac) the median anti-RBD titers decreased from 1025 to 242 AU/mL before the booster dose. In the heterologous group (primed with two doses of CoronaVac 4 weeks apart and a single booster dose of BNT162b2), the median anti-RBD titer increased to 31624 AU/mL, a 132-fold increase, 16 days after the booster dose. CONCLUSIONS: After the second dose of CoronaVac, protective neutralizing antibody levels decrease over time, and a booster dose is required. Heterologous COVID-19 booster vaccination with BNT162b2 is effective at boosting neutralizing antibody levels.

The Epidemiology of Influenza Virus Infection and Group A Streptococcal Pharyngitis in Children Between 2011 and 2018 in an Outpatient Pediatric Clinic.

Background The frequency of influenza virus infections and group A beta-hemolytic streptococcus (GAS) pharyngitis varies according to populations. We aimed to investigate the frequency of influenza virus and streptococcal pharyngitis infections in a pediatric outpatient cohort with many pediatric admissions in Istanbul. Materials and methods Children with upper respiratory tract infection (URTI) symptoms between 2011 and 2018 who underwent rapid diagnostic tests for influenza virus or streptococcal infection were evaluated retrospectively. Results The total number of pediatric cases admitted between 2011 and 2018 was 185,228, of which 119,928 were under five years old and 66,300 were children over five years old. The mean frequency of the influenza virus was 1,283 per 100,000 children, and the mean frequency of streptococcal pharyngitis was 1,764 per 100,000 children. The frequency of influenza has increased over the years. The frequency of streptococcal infection is higher in children over five years of age, and its frequency has decreased in this group. Conclusions The frequency of influenza virus infection and GAS pharyngitis varies according to years and seasons. Winter and spring were the seasons with the most frequent positive influenza virus and GAS pharyngitis. Although influenza frequency increased annually, this phenomenon was not observed in the frequency of GAS pharyngitis.

Efficiency of the sublingual route in treating B12 deficiency in infants.

Objective: To evaluate the efficiency of the sublingual route for the treatment of vitamin B12 deficiency in infants. Background: Vitamin B12 deficiency is common in children. In breastfed infants, the main reason is maternal B12 deficiency. Parenteral administration is commonly prescribed. However, patient compliance is not satisfactory due to repeated painful parenteral applications. It is also known that the oral route is efficient in high doses. In recent years, the sublingual route has been tried. This route stands out due to its easy applicability and low cost. However, there are few efficacy studies in infants for the sublingual route. Materials and methods: The study included 49 infants aged 6-12 months. All infants with marginal or deficient B12 levels (<300 pg/mL) were incidentally detected and treated with sublingual methylcobalamin. Each dose was 1000 µg and administered once a day in the first week, every other day in the second week, twice a week in the third week, and once a week in the last week. Serum vitamin B12 levels were measured before and after the treatment. Paired Sample T-Test was used to compare variables. Results: All infants had normal physical development and had no hematological or neurological issues. It was learned from the parents that the infants tolerated treatment well, and no side effects related to the treatment, such as vomiting or rash, were observed. Before and after the treatment, the mean vitamin B12 levels were 199±57 pg/mL and 684±336 pg/ml, respectively. The difference between the means was statistically significant (p<0.001). Conclusion: According to the study, it seems possible to treat vitamin B12 deficiency via a sublingual route in infants. In addition, methylcobalamin can be an alternative to the commonly used cyanocobalamin.

Comparison of immunogenicity and reactogenicity of inactivated SARS-CoV-2 vaccine (CoronaVac) in previously SARS-CoV-2 infected and uninfected health care workers.

The effects of inactivated SARS-CoV-2 vaccine (CoronaVac) on previously naturally infected individuals are unknown. This study compared immunogenicity and reactogenicity of CoronaVac in once naturally infected health-care workers (HCWs) and uninfected HCWs. All HCWs were immunized with two doses of CoronaVac (600 U/0.5 ml) intramuscularly at a 28-day interval. Adverse reactions were obtained by web-based questionnaires or telephone calls seven days after each vaccine dose. Detection of antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein was done four weeks after the second dose of the vaccine. We enrolled 103 previously naturally infected and 627 uninfected HCWs. The mean time for vaccination after the first nasopharyngeal SARS-CoV-2 positivity was 64 days (range: 15-136 days) in previously naturally infected HCWs. Among the previously naturally infected HCWs, 41 (40%) were asymptomatic, 52 (50%) had mild upper respiratory tract infections, 10 (105) had pneumonia, and only 6 (5%) were hospitalized. Any reported adverse reactions, either from the first dose or the second dose of vaccine administration, did not differ between previously infected and uninfected HCWs. Anti-RBD antibody titers were obtained in 50 (51%) of 103 previously infected HCWs and 142 (23%) of 627 uninfected HCWs. Anti-RBD antibody titers were significantly higher in HCWs with a previous natural infection (median 1220 AU/ml, range: 202-10328 AU/mL) than in uninfected HCWs (median: 913 AU/ml, range: 2.8-15547 AU/mL, p = .032). CoronaVac administration was safe and may elicit higher antibody responses in previously naturally infected individuals.

Nontypeable Haemophilus influenzae Otitis Media: Mastoiditis and Meningitis Complicated with Central Venous Thrombosis in an Immunocompetent Child.

Implementation of the Haemophilus influenzae type B (Hib) conjugate vaccine brought about a reduction in the number of cases and morbidity from type B but an increase in nontypeable strain infections. Nontypeable Haemophilus influenzae (NTHi) commonly colonizes children's upper respiratory tract and causes otitis media, sinusitis, and bronchitis. Invasive NTHi diseases, such as meningitis and septicemia, have rarely been reported. Herein, we discuss a previously healthy, fully immunized 3-year-old girl presented with otitis media and mastoiditis leading to meningitis caused by NTHi complicated with central venous thrombosis. She was treated with antibiotics, mastoidectomy and ventilation tube insertion, and anticoagulation therapy and recovered uneventfully. Through this case, we wish to share our unique clinical experience that NTHi should be born in mind as a potential pathogen that can cause meningitis in previously healthy children, which may be helpful in future cases.

Pediatricians' COVID-19 experiences and views on the willingness to receive COVID-19 vaccines: a cross-sectional survey in Turkey.

Developing an effective and safe vaccine against Covid-19 will facilitate return to normal. Due to hesitation toward the vaccine, it is crucial to explore the acceptability of the COVID-19 vaccine to the public and healthcare workers. In this cross-sectional survey, we invited 2251 pediatricians and 506 (22%) of them responded survey and 424 (84%) gave either nasopharyngeal swap or antibody assay for COVID-19 and 71 (14%) of them got diagnosis of COVID-19. If the effective and safe COVID-19 vaccine was launched on market, 420 (83%) of pediatrician accepted to get vaccine shot, 422 (83%) of them recommended vaccination to their family members, 380 (75%) of them accepted to vaccine their children and 445 (85%) of them offered vaccination to their pediatric patients. Among the participated pediatricians 304 (60%) of them thought COVID-19 vaccine should be mandatory. We found that there are high COVID-19 vaccine willingness rates for pediatricians for themselves, their own children, family members and their pediatric patients. We also found that being a pediatric subspecialist, believing in achieving an effective vaccine, willingness to participate in the phase 1-2 clinical vaccine trial, willingness to get an influenza shot this season, believing a vaccine and vaccine passport should be mandatory were significant factors in accepting the vaccine. It is important to share all information about COVID-19 vaccines, especially effectiveness and safety, with the public in a clear communication and transparency. The opposite will contribute to vaccine hesitancy and anti-vaccine movement.

Impact of self-financed rotavirus vaccination on acute gastroenteritis in young children in Turkey.

Rotavirus (RV) vaccines have been available in Turkey since 2006. These vaccines are not funded by the National Health System, so consequently their coverage rate in children has reached only 13-18%. We conducted a retrospective record review including all children ≤60 months of age presenting to study hospitals with suspected or clinical acute gastroenteritis (AGE) between 2012 and 2018. During the study, 109,605 children ≤60 months of age were admitted to pediatric out-patient clinics and pediatric emergency room, of which 15,501 (14%) were diagnosed with AGE. Incidence of RV-positive AGE decreased from 4.47 per 1,000 children in 2012 to 2.48 per 1,000 in 2018. A total of 4,805 (31%) such children were hospitalized with RV-positive AGE, a decrease from 1.9 per 1,000 children in 2012 to 0,45 per 1,000 in 2018. The length of hospital stays (LOS) of RV-positive AGE was 2.47 ± 1.15 days compared to LOS of RV-negative AGE 1.59 ± 1.17 days (p < .001). The overall cost of RV-positive AGE ($335 ± 200) was higher than that for RV-negative AGE ($280 ± 148) cases (p = .015). Vaccine effectiveness against any case of RV-positive AGE was 75,1% (95% CI: 65-86%). Despite the low level of vaccine coverage, the introduction of RV vaccination had a positive impact on the incidence of RV-positive AGE and related hospitalizations in young children.

Incidence of varicella and herpes zoster after inclusion of varicella vaccine in national immunization schedule in Turkey: time trend study.

The aim of the study was to investigate changes in the incidences of Varicella and Herpes Zoster (HZ) following introduction of single dose Varicella vaccine (VV) in Turkey. Changes in the incidences of varicella and HZ per 100,000 population were compared with pre (2011-2012) and post-VV period (2018-2019) throughout years between years 2011 and 2019 both for children and adults. In children ≤5 years of age, the annual incidences of varicella significantly decreased from 290 per 100000 children in 2011 to 24 per 100000 children in 2019 [p = .0001]. Also, for children ≤5 years the mean annual incidence of varicella decreased significantly [326/100000 ±51/100000 vs 23/100000 ± 1/100000; p = .014] between pre- and post-VV period. Moreover, the annual incidences of varicella significantly decreased from 43 per 100000 children in 2011 to 26 per 100000 children in 2019 in children age between 6 and 17 years. On the other hand, incidence of varicella in adult population (age >17 years) did not change significantly. Besides, the annual incidences of Herpes Zoster did not change significantly in children age stratas but significant increment observed in adult population. This increment was significant in adult age strata of 18-44 years, but non-significant in age strata of 45-64 years and >64 years. Thus, our study showed a significant reduction in the incidences of Varicella in children age stratas whereas significant increment in the incidence of HZ in adult population after the implementation of VV into the NIP of Turkey.

Comparison of Clinical and Laboratory Features and Treatment Options of 237 Symptomatic and Asymptomatic Children Infected with SARS-CoV-2 in the Early Phase of the COVID-19 Pandemic in Turkey.

Little is known about the therapeutic use of hydroxychloroquine in pediatric patients with coronavirus disease 2019 (COVID-19). Here, we retrospectively retrieved data of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PCR-positive pediatric patients from 20 hospitals in 8 Turkish cities. We obtained epidemiological, clinical, and laboratory features of the patients, as well as the drugs used for treating COVID-19. A total of 237 nasopharyngeal swab SARS-CoV-2 PCR-positive children were included in the study from March 26, 2020 to June 20, 2020. The mean age of asymptomatic children (118 ± 62 months) was higher than that of symptomatic children (89 ± 69 months). Symptomatic children had significantly lower mean lymphocyte counts and higher mean CRP, D-dimer, procalcitonin, and LDH levels than asymptomatic children in the univariate analysis. Among 156 children, 78 (50%), 15, 44, and 21 were treated with a hydroxychloroquine-containing regimen, hydroxychloroquine + azithromycin + oseltamivir, hydroxychloroquine + azithromycin, and hydroxychloroquine alone, respectively. Among 156 patients who received medical treatment, 90 (58%) underwent pre- and/or post-treatment electrocardiogram (ECG). However, none of them had ECG abnormalities or required hydroxychloroquine discontinuation due to adverse drug reactions.

The Use of Social Network in Daily Pediatric Practice and Education: Turkish Pediatric Atelier.

Using social media applications in pediatric education is not outdated, and its effectiveness has not been tested yet. For this reason, we shared the first results of the Pediatric Atelier experience that we realized through telegram application. We make an online survey to investigate the needs, requirements, pleasure, and suggestions of members through a web-based questionnaire. This cross-sectional survey study was delivered only to participants who were members of the workshop via their email addresses. Online questionnaires organized using Google Forms were sent to pediatric workshop members between March and June 2019. The questionnaire consisted of questions that measured the participants' basic demographic data, the use of the workshop, and the overall impact of the workshop on their professional behavior. While the institutions and positions of the participants were recorded, no other personal data (such as address and telephone) were collected. Among the 997 members, 417 (42%) of them answered the questionnaire. Respondents included 300 (72%) pediatrician, 21 (5%) pediatric subspeciality fellows, and 75 (18%) pediatric subspecialists. Of the 417 respondents, 217 (52%) were working in Istanbul, and 200 (48%) were working in other cities of Turkey. Among the responders, 233 (56%) were working in private hospitals or doctor offices. A total of 520 cases were consulted in 241 days of study period. Most consultations (n = 309, %59) were made from the Istanbul metropolitan area, and 203 (40%) consultations were from other cities of Turkey. The most frequently consulted departments were Pediatric infectious diseases: 166 (32%), Pediatric hematology and oncology: 56 (11%), and Neonatology: 43 (8%). Of the 520 consulted cases, 44 (8%) were related to life-threatening events, and 25 of them were hospitalized in the intensive care units, and 6 of them were required surgical operations. Of the 94% of responders thought this platform was useful and 82% of them stated that the case counseling part of the atelier was the most useful part. We think that the development of technology and artificial intelligence may lead to the usage of on-line platforms or systems in clinical medical practice. Clinical Trial Registration (if any). Registry name, registration number, web link to study on registry, and data sharing statement.

Response to "Letter to the Editor: Vaccine Failures in Pediatric Cases Caused by Streptococcus pneumoniae Serotype 19A".

We are happy to answer to the Letter from Ozkaya-Parlakay et al. to the Editor commenting on our recent paper, 1  investigated impact of the 13-valent pneumococcal conjugate vaccine (PCV13)  on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program (NIP) of Turkey.   Ozkaya-Parlakay et al. draw attention to vaccine failure and importance of continuous  surveillance of relevant disease especially in the perspective of  Streptococcus pneumoniae  serotype 19A. They supported their opinion by their clinical observation of seven children who were vaccinated with PCV13 developed empyema and meningitidis caused by Streptococcus pneumoniae  serotype 19A 
 in Turkey.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of community-acquired pneumonia and pneumonia-related hospitalizations in children ≤5 years after its implementation into the national immunization program of Turkey.

The aim of the study was to investigate changes in the incidences of community-acquired pneumonia (CAP) and CAP-related hospitalizations following introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in children ≤5 years of age into the national immunization programme (NIP) of Turkey. PCV7 was included in the NIP of Turkey in November 2008 and was replaced by PCV13 in late 2011. Changes in the incidences of CAP and CAP-related hospitalizations per 100,000 children admissions were investigated from 2011 to 2017. A total of 225,963 children visits were recorded; CAP was diagnosed in 4863 (2.15%) children and 1086 (22%) of them hospitalized between 2011 and 2017. The incidence of CAP declined from 5448 to 1144/100,000 from 2011 to 2017 (p = .001, r = -0.965). When the mean annual incidence of CAP between the transition period of PCV13 (2011/2012) was compared with a post-PCV13 period (2016/2017), CAP incidence was found to be 22% lower (p = .009). Also, the incidence of CAP-related hospitalization decreased significantly from 943 to 335/100,000 from 2011 to 2017 (p = .004 r = -0.91). Moreover, the mean incidence of CAP hospitalization declined 35% (p = .01) between the transition period of PCV13 and a post-PCV13 period. Thus, our study showed a significant reductions in the incidences of CAP and CAP-related hospitalization in children ≤5 years-old after the implementation of PCV13 into the NIP of Turkey.

Impact of the 13-valent pneumococcal conjugate vaccine on the incidences of acute otitis media, recurrent otitis media and tympanostomy tube insertion in children after its implementation into the national immunization program in Turkey.

The aim of this study was to investigate changes in the incidences of acute otitis media (AOM), recurrent AOM (rAOM) and tympanostomy tube (TT) insertion in children following the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national immunization program (NIP) of Turkey in April 2011. National coverage for the PCV7 was 97% in 2009, 93% in 2010, 96% in 2011 and for the PVC13 was 97% in 2012, 97% in 2013, 96% in 2014, 97% in 2015, 98% in 2016, and 96% in 2017 for Turkish children younger than 12 months of age. A total of 499932 pediatric visits were recorded, and AOM was diagnosed in 23005 (4.6%) children. The incidence of AOM in children ≤5 years of age decreased from 10700/100000 (2011) to 4712/100000 (2017), with a significant decreasing trend (p < .001, r = -0.965). When the mean annual incidences of AOM between the transition period of PCV13 (years 2011/2012) were compared with those of a post-PCV13 period (years 2016/2017) for children ≤5 years of age, the incidence of AOM was found to be decreased by 54% (p = 0.013). The mean incidence of TT insertion was found to be decreased by 65% (p = 0.003) between the transition period of PCV13 and a post-PCV13 period for children ≤5 years of age. On the other hand, rAOM incidence was found to be increased in whole pediatric age groups. Our study showed a significant decrease in the incidences of AOM and TT insertion in children ≤5 years old after implementation of PCV13 in the NIP in Turkey.

Fever-Associated Supraventricular Tachycardia after 4CMenB Vaccination in an Infant.

Meningococcal serogroup B vaccine 4CMenB (Bexsero) is a new four-component protein vaccine developed to prevent Neisseria meningitidis serogroup B infections. Case. We report a girl with fever and supraventricular tachycardia (SVT) 6-8 hours after the second dose of 4CMenB. SVT was unresponsive to the first dose of adenosine but terminated after the fourth dose of adenosine. During three months of follow-up, she was free of further SVT attacks. Conclusion. This is the first report of ECG-proven SVT after 4CMenB vaccination. Even if fever is coexistent, SVT should be considered after persistent tachycardia and 4CMenB vaccination.

Cardiopulmonary Resuscitation in Children With In-Hospital and Out-of-Hospital Cardiopulmonary Arrest: Multicenter Study From Turkey.

OBJECTIVES: The objectives of this study were to determine the causes, location of cardiopulmonary arrest (CPA) in children, and demographics of cardiopulmonary resuscitation (CPR) in Turkish pediatric emergency departments and pediatric intensive care units (PICUs) and to determine survival rates and morbidities for both in-hospital and out-of-hospital CPA. METHODS: This multicenter descriptive study was conducted prospectively between January 15 and July 15, 2011, at 18 centers (15 PICUs, 3 pediatric emergency departments) in Turkey. RESULTS: During the study period, 239 children had received CPR. Patients' average age was 42.4 (SD, 58.1) months. The most common cause of CPA was respiratory failure (119 patients [49.8%]). The location of CPA was the PICU in 168 (68.6%), hospital wards in 43 (18%), out-of-hospital in 24 (10%), and pediatric emergency department in 8 patients (3.3%). The CPR duration was 30.7 (SD, 23.6) minutes (range, 1-175 minutes) and return of spontaneous circulation was achieved in 107 patients (44.8%) after the first CPR. Finally, 58 patients (24.2%) were discharged from hospital; survival rates were 26% and 8% for in-hospital and out-of-hospital CPA, respectively (P = 0.001). Surviving patients' average length of hospital stay was 27.4 (SD, 39.2) days. In surviving patients, 19 (32.1%) had neurologic disability. CONCLUSION: Pediatric CPA in both the in-hospital and out-of-hospital setting has a poor outcome.

Therapeutic plasma exchange for malignant refractory status epilepticus: a case report.

BACKGROUND: Refractory status epilepticus is a prolongation of status epilepticus despite anticonvulsant therapy with two or three medications in proper doses; it is defined as malignant status epilepticus if it takes weeks or months. Intravenous immunoglobulin, high-dose steroids, magnesium infusion, pyridoxine, hypothermia, ketogenic diet, electroconvulsive therapy, and surgical therapy are the other treatment options for status epilepticus. PATIENT: Our 5-year-old male patient was hospitalized at our pediatric intensive care unit because of status epilepticus secondary to meningoencephalitis. No response could be obtained with many medical and nonmedical therapies in our patient, who developed malignant status epilepticus with unknown etiology. Therapeutic plasma exchange was applied as convulsions continued. RESULT: Ours is the first child for whom therapeutic plasma exchange was successfully applied because of malignant refractory status epilepticus secondary to meningoencephalitis. CONCLUSION: Therapeutic plasma exchange may be a treatment option for children with refractory status epilepticus following presumed meningoencephalitis.

Evaluation of endocrine function in children admitted to pediatric intensive care unit.

BACKGROUND: Although studied widely in adulthood, little is known about endocrinological disorders during critical illnesses in childhood. The aims of this study were to define the endocrinological changes in patients admitted to pediatric intensive care unit (PICU) and to identify their effects on prognosis. METHODS: Forty patients with a mean age of 5.1 years admitted to PICU were enrolled in the study. Blood samples were taken at admission and at 24 and 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient's condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores. RESULTS: PRISM and PELOD scores were significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP-3 and IL-6 were not significantly different between the survivors and non-survivors. There was a negative correlation between baseline IGFBP-3 and PRISM scores. A positive correlation was seen between cortisol level at 24 h and PRISM score. On multivariate linear regression analysis, PRISM score was best explained by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL-6 at 24 h and PELOD scores. CONCLUSIONS: Although there was no difference between survivors and non-survivors regarding the studied endocrine parameters, there were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment scores, and, given that these scores correlated with mortality, these parameters might be useful as prognostic factors.

Hyperferritinemia in the critically ill child with secondary hemophagocytic lymphohistiocytosis/sepsis/multiple organ dysfunction syndrome/macrophage activation syndrome: what is the treatment?

INTRODUCTION: Hyperferritinemia is associated with increased mortality in pediatric sepsis, multiple organ dysfunction syndrome (MODS), and critical illness. The International Histiocyte Society has recommended that children with hyperferritinemia and secondary hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) should be treated with the same immunosuppressant/cytotoxic therapies used to treat primary HLH. We hypothesized that patients with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS can be successfully treated with a less immunosuppressant approach than is recommended for primary HLH. METHODS: We conducted a multi-center cohort study of children in Turkish Pediatric Intensive Care units with hyperferritinemia associated secondary HLH/sepsis/MODS/MAS treated with less immunosuppression (plasma exchange and intravenous immunoglobulin or methyl prednisolone) or with the primary HLH protocol (plasma exchange and dexamethasone or cyclosporine A and/or etoposide). The primary outcome assessed was hospital survival. RESULTS: Twenty-three children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS were enrolled (median ferritin = 6341 µg/dL, median number of organ failures = 5). Univariate and multivariate analyses demonstrated that use of plasma exchange and methyl prednisolone or intravenous immunoglobulin (n = 17, survival 100%) was associated with improved survival compared to plasma exchange and dexamethasone and/or cyclosporine and/or etoposide (n = 6, survival 50%) (P = 0.002). CONCLUSIONS: Children with hyperferritinemia and secondary HLH/sepsis/MODS/MAS can be successfully treated with plasma exchange, intravenous immunoglobulin, and methylprednisone. Randomized trials are required to evaluate if the HLH-94 protocol is helpful or harmful compared to this less immune suppressive and cytotoxic approach in this specific population.

Hypophosphatemia and its clinical implications in critically ill children: a retrospective study.

PURPOSE: The aims of this study were to determine the prevalence of hypophosphatemia and to discuss the clinical implications of hypophosphatemia in critically ill children. MATERIALS AND METHODS: A retrospective review of the medical records of children admitted to the pediatric intensive care unit from December 2006 to December 2007 was conducted. RESULTS: In 60.2% (n = 71) of the patients, any serum phosphorous level at admission and at the third day or seventh day after admission to pediatric intensive care unit was in hypophosphatemic range. Sepsis was present in 22.9% (n = 27) of the children studied and was associated with hypophosphatemia (P = .02). Hypophosphatemia was also associated with use of furosemide (P = .04), use of steroid (P = .04), use of ß(2) agonist (P = .026), and use of an H(2) blocker (P = .004). There was a significant association between hypophosphatemia and the rate to attain target caloric requirements by enteral route (P = .007). The median time to attain target caloric requirements by enteral route was 2.9 ± 1.9 (0.2-10) days in the normophosphatemic group and 4.4 ± 2.8 (0.3-12) days in the hypophosphatemic group. In the multiple regression model, solely the rate to attain the target caloric requirements by enteral route demonstrated independent association with hypophosphatemia (P = .006; ß = .27; 95% confidence interval, 0.02-0.09). Significant association was found between hypophosphatemia and the duration of mechanical ventilation and between hypophosphatemia and pediatric intensive care unit length of stay (P = .02 and P = .001, respectively). CONCLUSIONS: Critically ill pediatric patients are prone to hypophosphatemia, especially if they cannot be fed early by enteral route. Hypophosphatemia is associated with an increased duration of mechanical ventilation and increased length of stay in the pediatric intensive care unit, suggesting that active repletion might improve these parameters.

Critically ill children with pandemic influenza (H1N1) in pediatric intensive care units in Turkey.

OBJECTIVES: To outline the epidemiologic features, clinical presentation, clinical courses, and outcomes in critically ill children with pandemic influenza in pediatric intensive care units. DESIGN: Retrospective, observational, multicenter study. SETTING: Thirteen tertiary pediatric intensive care units in Turkey. PATIENTS: Eighty-three children with confirmed infection attributable to pandemic influenza detected by reverse-transcriptase polymerase chain reaction assay between November 1 and December 31, 2009 who were admitted to critical care units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During a 2-month period, 532 children were hospitalized with pandemic influenza and 83 (15.6%) needed critical care. For the 83 patients requiring critical care, the median age was 42 (range, 2-204) months, with 24 (28.9%) and 48 (57.8%) of patients younger than 2 and 5 yrs, respectively. Twenty (24.1%) patients had no underlying illness, but 63 (75.9%) children had an underlying chronic illness. Indications for admission to the pediatric intensive care unit were respiratory failure in 66 (79.5%), neurologic deterioration in six (7.2%), and gastrointestinal symptoms in five (6.0%) patients. Acute lung injury was diagnosed in 23 (27.7%), acute respiratory distress syndrome was diagnosed in 34 (41%), and 51 (61.4%) patients were mechanically ventilated. Oseltamivir was used in 80 (96%) patients. The mortality rate for children with pandemic influenza 2009 was 30.1% compared to an overall mortality rate of 13.7% (p = .0016) among pediatric intensive care unit patients without pandemic influenza during the study period. Also, the mortality rate was 31.7% in patients with comorbidities and 25.0% in previously healthy children (p = .567). The cause of death was primary pandemic influenza infection in 16 (64%), nosocomial infection in four (16%), and primary disease progression in five (20%) patients. The odds ratio for respiratory failure was 14.7 (95% confidence interval, 1.85-111.11), and odds ratio for mechanical ventilation was 27.7 (95% confidence interval, 0.003-200). CONCLUSIONS: Severe disease and high mortality rates were seen in children with pandemic influenza. Death attributable to pandemic influenza occurred in all age groups of children with or without underlying illness. Multiple organ dysfunction syndrome is associated with increased mortality, and death is frequently secondary to severe lung infection caused by pandemic influenza.