Epidemiology of pediatric severe sepsis and septic shock in Turkey: Prevalence, Results and Treatments Study.

AIM: This study was aimed at characterizing the prevalence, management, and outcomes of pediatric severe sepsis and septic shock in tertiary pediatric intensive care units (PICUs) in Turkey. METHODS: A point prevalence study was conducted on five days over the course of one year in 29 PICUs in Turkey. Outcomes included severe sepsis and septic shock point prevalence, therapies used, duration of PICU stay, and mortality at day 28. RESULTS: Of the 1757 children who were admitted to the PICU during the study period, 141 (8.0%) children met the consensus criteria for severe sepsis and 23 (1.3%) children met the criteria for septic shock. Pediatric severe sepsis and septic shock accounted for 8% and 1.3% of all PICU admissions, respectively. The median age of the patients was 2.6 years (interquartile range (IQR), 0.7-8.6 years). Enteral nutrition (79.3%) was preferred compared to parenteral nutrition (31.1%) for the first 3 days after PICU admission. A total of 39 patients died while in the PICU, for a 23.8% mortality rate, which did not vary by age. CONCLUSION: The mortality rate was similar to that in other studies. Hematologic-immunologic comorbidity, parenteral nutrition and the use of vasoactive drugs were independently associated with mortality.

Daily Practice of Mechanical Ventilation and Weaning in Turkish PICUs: A Multicenter Prospective Survey.

OBJECTIVES: To investigate conventional mechanical ventilation weaning characteristics of patients requiring conventional mechanical ventilation support for greater than 48 hours within the PICU. DESIGN: The prospective observational multicenter cohort study was conducted at 15 hospitals. Data were being collected from November 2013 to June 2014, with two designated researchers from each center responsible for follow-up and data entry. SETTING: Fifteen tertiary PICUs in Turkey. PATIENTS: Patients between 1 month and 18 years old requiring conventional mechanical ventilation for greater than 48 hours were included. A single-center was not permitted to surpass 20% of the total sample size. Patients with no plans for conventional mechanical ventilation weaning were excluded. INTERVENTIONS: Conventional mechanical ventilation MEASUREMENTS AND MAIN RESULTS:: Pertinent variables included PICU and patient demographics, including clinical data, chronic diseases, comorbid conditions, and reasons for intubation. Conventional mechanical ventilation mode and weaning data were characterized by daily ventilator parameters and blood gases. Patients were monitored until hospital discharge. Of the 410 recruited patients, 320 were included for analyses. A diagnosis of sepsis requiring intubation and high initial peak inspiratory pressures correlated with a longer weaning period (mean, 3.65 vs 1.05-2.17 d; p < 0.001). Conversely, age, admission Pediatric Risk of Mortality III scores, days of conventional mechanical ventilation before weaning, ventilator mode, and chronic disease were not related to weaning duration. CONCLUSIONS: Pediatric patients requiring conventional mechanical ventilation with a diagnosis of sepsis and high initial peak inspiratory pressures may require longer conventional mechanical ventilation weaning prior to extubation. Causative factors and optimal weaning for this cohort needs further consideration.

Early initiated feeding versus early reached target enteral nutrition in critically ill children: An observational study in paediatric intensive care units in Turkey.

AIM: Although early enteral nutrition (EN) is strongly associated with lower mortality in critically ill children, there is no consensus on the definition of early EN. The aim of this study was to evaluate our current practice supplying EN and to identify factors that affect both the initiation of feeding within 24 h after paediatric intensive care unit (PICU) admission and the adequate supply of EN in the first 48 h after PICU admission in critically ill children. METHODS: We conducted a prospective, multicentre, observational study in nine PICUs in Turkey. Any kind of tube feeding commenced within 24 h of PICU admission was considered early initiated feeding (EIF). Patients who received more than 25% of the estimated energy requirement via enteral feeding within 48 h of PICU admission were considered to have early reached target EN (ERTEN). RESULTS: Feeding was initiated in 47.4% of patients within 24 h after PICU admission. In many patients, initiation of feeding seems to have been delayed without an evidence-based reason. ERTEN was achieved in 43 (45.3%) of 95 patients. Patients with EIF were significantly more likely to reach ERTEN. ERTEN was an independent significant predictor of mortality (P < 0.001), along with reached target enteral caloric intake on day 2 associated with decreased mortality. CONCLUSIONS: There is a substantial variability among clinicians' perceptions regarding indications for delay to initiate enteral feeding in critically ill children, especially after the first 6 h of PICU admission. ERTEN, but not EIF, is associated with a significantly lower mortality rate in critically ill children.

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.

Erythropoietin prevents lymphoid apoptosis but has no effect on survival in experimental sepsis.

BACKGROUND: Lymphoid apoptosis in sepsis is associated with poor outcome, and prevention of apoptosis frequently improves survival in experimental models of sepsis. Recently, erythropoietin (EPO) was shown to protect against lipopolysaccharide (LPS)-induced mortality. As cecal ligation and puncture (CLP) is a clinically more relevant model of sepsis, we evaluated the effect of EPO on CLP-induced lymphoid tissue apoptosis and mortality. METHODS: Young Wistar rats were subjected to polymicrobial sepsis by CLP. EPO (5,000 U/kg intraperitoneal) was administered 30 min before CLP and then 1 and 4 h after CLP. Spleen, thymus, and small intestine were harvested at 24 h and assessed for apoptosis by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) and caspase-3 staining. A separate group of animals was followed up for mortality. RESULTS: Splenic, thymic, and intestinal apoptosis was increased after CLP; administration of EPO significantly decreased apoptosis as determined by TUNEL and caspase-3 staining. Final survival in the CLP mortality study was 30% in both saline and EPO groups. CONCLUSION: Our results provide the first evidence that EPO attenuates lymphoid apoptosis in the CLP model of sepsis. However, EPO is not associated with a survival benefit in the CLP model of sepsis.

Acute Fulminant Hepatic Failure Caused by Sevoflurane Linked to Influenza A.

Sevoflurane is a volatile anesthetic agent that does not tend to cause clinically significant hepatotoxicity, but there are some reported hepatotoxicity cases in the literature. In the case presented here, adenotonsillectomy was performed during influenza infection, and sevoflurane was administered, after which acute fulminant hepatitis developed. At hour 24 of hospitalization after fulminant hepatic failure, liver transplant was performed in a 3.5-year-old patient without any known diseases. In such cases, etiology investigations should be planned, life support therapy should be administered, and information should be given to the patient to avoid exposure to sevoflurane in the future.

A new Late Miocene Hystrix (Hystricidae, Rodentia) from Turkey.

The Çorakyerler fossil locality in Anatolia reveals unique faunal elements. This study introduces Hystrix kayae sp. nov., a new Late Miocene porcupine initially classified as Hystrix sp. Yavuz et al., 2018. This finding expands our knowledge of Late Miocene Anatolian porcupines, bringing the total number of known species to three. H. kayae sp. nov. is larger than Hystrix aryanensis and exhibits greater upper cheek tooth crown height. Its cheek tooth morphology differs from Hystrix depereti, and it possesses distinctive U-shaped choanae unlike Hystrix primigenia. The Çorakyerler locality may predate sites with H. aryanensis and H. primigenia but aligns temporally with Hystrix parvae localities. This study enhances our understanding of Late Miocene porcupine diversity in Anatolia, emphasizing the importance of Çorakyerler in unraveling the evolutionary history of these fascinating mammals.

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.

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.

An intoxication mimicking brain death: baclofen.

Baclofen is a derivative of gamma-aminobutyric acid, used mainly for the treatment of muscle spasticity. Baclofen overdose can result in severe respiratory depression, autonomic disturbances, seizures and coma. Here we report a 15-year-old girl who was found unresponsive, intubated and admitted to the PICU. On initial presentation, her Glasgow Coma Score was 3, with fixed dilated pupils. EEG revealed cerebral bioelectric activity and ground amplitudes significantly lower than normal. Supportive treatments were administered. On the 2nd PICU day, she regained consciousness and was able to follow commands. She was extubated and discharged on hospital day 3. Conclusively emergency physicians should consider baclofen overdose in children presenting with acute loss of consciousness, flaccidity, and hyporeflexia.

Delayed renal excretion of methotrexate after a severe anaphylactic reaction to methotrexate in a child with osteosarcoma.

Although methotrexate is an agent widely used in the practice of pediatric oncology, allergic reactions to methotrexate are most unusual. Most of these reactions typically occur after repeated administration. Here, we report a severe anaphylactoid reaction to the first dose of high-dose methotrexate infusion in a child with osteosarcoma who has also experienced a delayed excretion of methotrexate. Clinicians must be aware of the possibility of a systemic, near-fatal anaphylactic reactions with methotrexate and patients who experience severe anaphylactic reactions should be followed carefully because of the possibility of delayed methotrexate excretion.

A survey of pediatric intensive care services in Turkey.

The aim of this study was to describe and assess the structure, organization, and staffing of pediatric intensive care services in Turkey. A survey was sent to major university and government hospitals. Out of the 40 hospitals stating to provide pediatric intensive care, 34 responded to the survey (85% response rate). In the majority (81.2%) of hospitals, pediatric intensive care was provided in single room units or within the pediatric ward. Unit size ranged from 1-16 beds with an average of 6.8 +/- 4.2 operational beds per unit. Much of the equipment and a sufficient number of specialists for pediatric intensive care unit (PICU) care were present in the surveyed hospitals. However, only 12 units had a pediatric intensivist on staff and few had special PICU nurses. Many hospitals in Turkey already have various equipment and specialists needed to support pediatric intensive care. Expansion of services and improved care could be achieved if more pediatric intensivists and nurses could be provided and services concentrated in fully equipped tertiary centers.

The prevalance of and factors associated with intra-abdominal hypertension on admission day in critically ill pediatric patients: A multicenter study.

PURPOSE: To investigate admission prevalence of intraabdominal hypertension (IAH) and to determine clinical and laboratory characteristics on admission day associated with IAH in critically ill pediatric patients. MATERIALS AND METHODS: One hundred thirty newly admitted critically ill pediatric patients were included. Intra-abdominal pressure (IAP) was measured 4 times (every 6 hours) with the bladder pressure method. Data included the demographics, diagnostic category, pediatric logistic organ dysfunction score and pediatric risk of mortality score II, clinical concomitant factors, and conditions potentially associated with increased intra-abdominal pressure. RESULTS: Seventy patients (56.1%) had a normal IAP (≤10 mmHg, mean IAP [mmHg] 7.18 ± 1.85), while 60 patients (43.9%) had IAP >10 mmHg (mean IAP [mmHg] 15.46 ± 5.21). Hypothermia frequency, lactate levels, number of patients with oligo-anuria, and mechanical ventilation requirement were higher among patients with IAH compared to patients without IAH (both, P< .05). Hypothermia (OR, 3.899; 95% CI, 1.305-11.655; P< .03) and lactate levels (OR, 1.283 for each mmol/L increase; 95% CI, 1.138-1.447; P< .001) were only significantly associated with IAH. CONCLUSIONS: Intra-abdominal hypertension seems to affect nearly half of newly admitted critically ill pediatric patients. Lactate level and the presence of hypothermia seem to be the independent predictors of the presence of IAH.

RNA interference in neuroscience.

One of the most exciting findings in recent years has been the discovery of RNA interference (RNAi). RNAi is an important system that allows sequence-specific gene silencing through targeted degradation of mRNA by cognate double-stranded RNA (dsRNA). RNAi plays a role in endogenous cellular processes, such as developmental control and heterochromatin formation, and serves as an antiviral defense mechanism. Recent findings suggest that RNAi and related pathways are involved in protecting the genome against instabilities caused by transposons and repetitive sequences. Several rapidly developing RNAi methodologies provide a new approach for elucidation of gene functions. RNAi technology is also currently being evaluated as a potentially useful method to develop highly specific dsRNA-based gene-silencing therapeutics. In this paper, we review the use of RNAi in neuroscience research and as a possible therapeutic tool for treatment of neurological diseases.

Erythropoietin as a novel neuroprotectant.

PURPOSE: To provide an overview of the current knowledge on neuroprotective properties of Erythropoietin (Epo), mechanisms by which Epo produces neuroprotection, and signaling pathways regulated by Epo in the nervous system. METHODS: The Medline database was searched for articles on the neuroprotective properties of Epo. Experimental and clinical studies were systematically reviewed. RESULTS: In addition to promoting the survival, proliferation, and differentiation of immature erythroid cells, Epo and the Epo receptor (EpoR) have recently been shown to exist and function in the nervous system. The Epo/EpoR system plays a critical role in neurodevelopment and neuroprotection. Epo ameliorates or prevents neuronal injury by neuroprotective, anti-apoptotic, anti-inflammatory, anti-oxidant, angiogenic, neurogenic and neurotrophic effects in cell culture and animal models of neurological diseases. The clinical effectiveness of recombinant human Epo in ischemic stroke in human patients has also been reported recently. CONCLUSION: Recent studies suggest that Epo is a potential novel neurotherapeutic agent and further clinical studies are warranted.

Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia-ischemia in rats.

It is well known that neonatal hypoxic-ischemic brain injury leads to mental retardation and deficits in cognitive abilities such as learning and memory in human beings. The ameliorative effect of erythropoietin (Epo) on experimental hypoxic-ischemic brain injury in neonatal rats has been recently reported. However, the effect of Epo on cognitive abilities in the hypoxic-ischemic brain injury model is unknown. The aim of this study is to investigate the effects of Epo on learning-memory, behavior and neurodegeneration induced by hypoxia-ischemia. Seven days old Wistar Albino rat pups have been used in the study (n = 28). Experimental groups in the study were: (1) saline-treated hypoxia-ischemia group, (2) Epo-treated (i.p., 1000 U/kg) hypoxia-ischemia group, (3) sham-operated group, (4) control group. In hypoxia-ischemia groups, left common carotid artery was ligated permanently on the seventh postnatal day. Two hours after the procedure, hypoxia (92% nitrogen and 8% oxygen) was induced for 2.5 h. Epo was administered as a single dose immediately after the hypoxia period. When pups were 22 days old, learning experiments were performed using Morris water maze. On the 20th week, when brain development is accepted to be complete, learning experiments were repeated. Rats were then perfused and brains removed for macroscopic and microscopic evaluation. Epo treatment immediately after hypoxic-ischemic insult significantly improved long-term neurobehavioral achievements when tested during the subsequent phase of brain maturation and even into adulthood. Histopathological evaluation demonstrated that Epo also significantly diminished brain injury and spared hippocampal CA1 neurons. In conclusion, Epo administrated as a single dose immediately after neonatal hypoxic-ischemic insult provides benefit over a prolonged period in the still developing rat brain. Since the wide use of Epo in premature newborns, this agent may be potentially beneficial in treating asphyxial brain damage in the perinatal period.

Erythropoietin and the nervous system.

Erythropoietin (Epo) is a hematopoietic growth factor and cytokine which stimulates erythropoiesis. In recent years, Epo has been shown to have important nonhematopoietic functions in the nervous system. Nonerythropoietic actions of Epo include a critical role in the development, maintenance, protection and repair of the nervous system. A wide variety of experimental studies have shown that Epo and its receptor are expressed in the nervous system and Epo exerts remarkable neuroprotection in cell culture and animal models of nervous system disorders. In this review, we summarize the current knowledge on the neurotrophic and neuroprotective properties of Epo, the mechanisms by which Epo produces neuroprotection and the signal transduction systems regulated by Epo in the nervous system.

Severe neurologic involvement of Degos disease in a pediatric patient.

A 14-year-old male presented with paresthesias on the right upper and lower extremities, headache, and vomiting. In addition to worsening paresthesia and weakness on the right side of his body, blurred vision, fever, and skin lesions developed. He also had skin lesions characterized with 3-10 mm papules with a white atrophic center surrounded by pink rim mostly on the trunk and lower extremities. Brain magnetic resonance imaging showed chronic subdural effusion and encephalomalacia of the left cerebral hemisphere. Cerebrospinal fluid (CSF) examination revealed increased protein levels. Electromyography was consistent with diffuse polyradiculoneuropathy. Skin biopsy confirmed the diagnosis of a rare vasculopathy: Degos disease. A case presenting with chronic subdural effusion, encephalomalacia, elevated CSF protein, and polyradiculopathy should be carefully examined for skin lesions, which may suggest the diagnosis of Degos disease.