Chronic rhinosinusitis with nasal polyposis and biological agents: the ARIA-ITALY Survey.

Summary: Background. Chronic rhinosinusitis (CRS) is an inflammatory disease that affects the nasal mucosa and the paranasal sinuses. CRS can be associated by nasal polyposis (CRSwNP phenotype) in up to 30% of patients and it is frequently associated with bronchial asthma. CRSwNP shows predominantly an underlying activation of type 2 inflammatory pathways with the involvement of eosinophils, IgE, interleukin (IL)-4, IL-5 and IL-13. Biological drugs that target these inflammatory cytokines are currently a therapeutic option recognized by guidelines for the treatment of uncontrolled form of the disease. Methods. As part of the activity of the "ARIA-Italy" working group, a panel of 255 Italian Ear, Nose and Throat (ENT) specialists, pneumologists and immuno-allergologists actively participated in this national survey and answered a series of questions geared toward understanding the main criteria for patient characterization and therapeutic decision, highlighting multidisciplinarity, and the implementation of the management of CRSwNP patients, as a part of the precision medicine concept and the appropriate use of the biologicals. Results. Two hundred and fifty-five experts and specialists participated in the survey. Conclusions. The results of this survey obtained from an extensive number of active specialists throughout Italy allow some important concluding remarks to be drawn. The main points of agreement were that multidisciplinary care teams provide many benefits but that, once the team is established, meetings and communication between members must be coordinated. Finally, the dissemination of national disease registries and the continuous updating of guidelines and position papers related to CRSwNP and comorbidities should be encouraged.

The Role of the Anesthesiologist and the Modern Intraoperative Echography in Ventriculoatrial Shunt for Hydrocephalus: From Hakim to Nowadays.

The introduction of US-guided venipuncture in clinical practice has greatly facilitated the surgical approach to patients with hydrocephalus. Especially in infants and children, where it results in a lower technical failure rate, less time and fewer complications than the traditional referral method, this technique has become a clinical protocol. This dynamic or "real time" technique has become one of the anesthetist's tools. This allowed the anesthesiologists to be part of the surgical team, so they not only dedicate themselves to inducing and maintaining general anesthesia but also to performing venipuncture of the central vein of the neck and to locating the tip of the catheter.The anesthetist's tools have made it possible to perform a simple and safe method, and the anesthesiologists have become an active part of the surgical team, charged with a specific role during the positioning of the ventricular atrial shunt.

Early abnormal fibrinolysis and mortality in patients with thermal injury: a prospective cohort study.

INTRODUCTION: Abnormal fibrinolysis early after injury has been associated with increased mortality in trauma patients, but no studies have addressed patients with burn injury. This prospective cohort study aimed to characterize fibrinolytic phenotypes in burn patients and to see if they were associated with mortality. METHODS: Patients presenting to a regional burn centre within 4 h of thermal injury were included. Blood was collected for sequential viscoelastic measurements using thromboelastography (RapidTEG™) over 12 h. The percentage decrease in clot strength 30 min after the time of maximal clot strength (LY30) was used to categorize patients into hypofibrinolytic/fibrinolytic shutdown (SD), physiological (PHYS) and hyperfibrinolytic (HF) phenotypes. Injury characteristics, demographics and outcomes were compared. RESULTS: Of 115 included patients, just over two thirds were male. Overall median age was 40 (i.q.r. 28-57) years and median total body surface area (TBSA) burn was 13 (i.q.r. 6-30) per cent. Some 42 (36.5 per cent) patients had severe burns affecting over 20 per cent TBSA. Overall mortality was 18.3 per cent. At admission 60.0 per cent were PHYS, 30.4 per cent were SD and 9.6 per cent HF. HF was associated with increased risk of mortality on admission (odds ratio 12.61 (95 per cent c.i. 1.12 to 142.57); P = 0.041) but not later during the admission when its incidence also decreased. Admission SD was not associated with mortality, but incidence increased and by 4 h and beyond, SD was associated with increased mortality, compared with PHYS (odds ratio 8.27 (95 per cent c.i. 1.16 to 58.95); P = 0.034). DISCUSSION: Early abnormal fibrinolytic function is associated with mortality in burn patients.

FID Score: an effective tool in Hereditary Haemorrhagic Telangiectasia - related epistaxis.

BACKGROUND: Hereditary haemorrhagic telangiectasia (HHT) is a rare disease characterized by a multisystemic vascular dysplasia and epistaxis, that is the most common cause of disability and social impairment. Patient management strictly depends on the severity of this symptom; therefore, it is of paramount importance for the clinicians to effectively grade epistaxis severity. The aim of this report was to validate the Frequency, Intensity and Duration score (FID) for grading epistaxis severity in patients with HHT; we studied repeatability and external validity comparing FID score with Epistaxis Severity Score (ESS). METHODS: This is a descriptive, observational study that included 264 adult HHT patients with epistaxis. Diagnosis of HHT was established with Curacao criteria or positivity at genetic testing. Nosebleed severity was evaluated according to the FID score and the ESS. The first 30 patients were included in the validation of the FID score, which was graded on days 0, 1, 3 and 7. In the remaining 234 patients, a comparison between the ESS and FID score was performed. RESULTS: The statistical analysis performed in order to validate the FID score showed very good agreement between scores calculated on different days; analysis comparing the FID score with the ESS revealed a high correlation between the two grading systems. CONCLUSIONS: The FID score is a quick, easy and precise tool for evaluating HHT-related epistaxis and could be a possible alternative to the ESS. The FID score meets the need for an intuitive and smart grading system that is easy to manage in clinicians’ hands.

Elevation of circulating microRNA levels in obese children compared to healthy controls.

As childhood obesity increases, it is becoming important to understand the complications of obesity in children and develop novel biomarkers. Evidence indicates that microRNAs (miRNA) are dys-regulated in obesity and may serve as sensitive and specific circulating biomarkers. Non-alcoholic fatty liver disease (NAFLD) is a complication of obesity that ultimately requires a liver biopsy to determine disease severity. While studies have been conducted in adults, no study to date has examined circulating miRNAs in children with obesity and NAFLD. The goal of this study was to evaluate a panel of selected circulating miRNAs in obese children compared to healthy controls. We present here an analysis of a pre-selected panel of 20 candidate miRNAs in obese children compared to healthy controls. The miRNAs were chosen based on having been previously reported to be involved in NAFLD. We found that 16 out of 20 miRNAs tested were elevated at least twofold in children with obesity compared to controls. miR-122 and miR-199a showed the greatest increase in children with obesity versus controls. Both also had a high area under the curve when receiver-operator curves were plotted. Several circulating miRNAs correlated with body mass index (BMI) or serum transaminases. This study provides initial evidence that circulating miRNAs can be measured in the paediatric population and provides several diagnostic candidates increased in children with obesity that may be relevant to NAFLD.

Effects of an acidic environment on coagulation dynamics.

Essentials Acidosis, an outcome of traumatic injury, has been linked to impaired procoagulant efficiency. In vitro model systems were used to assess coagulation dynamics at pH 7.4 and 7.0. Clot formation dynamics are slightly enhanced at pH 7.0 in blood ex vivo. Acidosis induced decreases in antithrombin efficacy offset impairments in procoagulant activity. SUMMARY: Background Disruption of hydrogen ion homeostasis is a consequence of traumatic injury often associated with clinical coagulopathy. Mechanisms by which acidification of the blood leads to aberrant coagulation require further elucidation. Objective To examine the effects of acidified conditions on coagulation dynamics using in vitro models of increasing complexity. Methods Coagulation dynamics were assessed at pH 7.4 and 7.0 as follows: (i) tissue factor (TF)-initiated coagulation proteome mixtures (±factor [F]XI, ±fibrinogen/FXIII), with reaction progress monitored as thrombin generation or fibrin formation; (ii) enzyme/inhibitor reactions; and (iii) TF-dependent or independent clot dynamics in contact pathway-inhibited blood via viscoelastometry. Results Rate constants for antithrombin inhibition of FXa and thrombin were reduced by ~ 25-30% at pH 7.0. At pH 7.0 (+FXI), TF-initiated thrombin generation showed a 20% increase in maximum thrombin levels and diminished thrombin clearance rates. Viscoelastic analyses showed a 25% increase in clot time and a 25% reduction in maximum clot firmness (MCF). A similar MCF reduction was observed at pH 7.0 when fibrinogen/FXIII were reacted with thrombin. In contrast, in contact pathway-inhibited blood (n = 6) at pH 7.0, MCF values were elevated 6% (95% confidence interval [CI]: 1%-11%) in TF-initiated blood and 15% (95% CI: 1%- 29%) in the absence of TF. Clot times at pH 7.0 decreased 32% (95% CI: 15%-49%) in TF-initiated blood and 51% (95% CI: 35%-68%) in the absence of TF. Conclusions Despite reported decreased procoagulant catalysis at pH 7.0, clot formation dynamics are slightly enhanced in blood ex vivo and suppression of thrombin generation is not observed. A decrease in antithrombin reactivity is one potential mechanism contributing to these outcomes.

Early hemostatic responses to trauma identified with hierarchical clustering analysis.

BACKGROUND: Trauma-induced coagulopathy is a complex multifactorial hemostatic response that is poorly understood. OBJECTIVES: To identify distinct hemostatic responses to trauma and identify key components of the hemostatic system that vary between responses. PATIENTS/METHODS: A cross-sectional observational study of adult trauma patients at an urban level I trauma center emergency department was performed. Hierarchical clustering analysis was used to identify distinct clusters of similar subjects according to vital signs, injury/shock severity, and comprehensive assessment of coagulation, clot formation, platelet function, and thrombin generation. RESULTS: Among 84 total trauma patients included in the model, three distinct trauma clusters were identified. Cluster 1 (N = 57) showed platelet activation, preserved peak thrombin generation, plasma coagulation dysfunction, a moderately decreased fibrinogen concentration and normal clot formation relative to healthy controls. Cluster 2 (N = 18) showed platelet activation, preserved peak thrombin generation, and a preserved fibrinogen concentration with normal clot formation. Cluster 3 (N = 9) was the most severely injured and shocked, and showed a strong inflammatory and bleeding phenotype. Platelet dysfunction, thrombin inhibition, plasma coagulation dysfunction and a decreased fibrinogen concentration were present in this cluster. Fibrinolytic activation was present in all clusters, but was particularly increased in cluster 3. Trauma clusters were most noticeably different in their relative fibrinogen concentration, peak thrombin generation, and platelet-induced clot contraction. CONCLUSIONS: Hierarchical clustering analysis identified three distinct hemostatic responses to trauma. Further insights into the underlying hemostatic mechanisms responsible for these responses are needed.

Posterior lacrimal sac approach technique without stenting in endoscopic dacryocystorhinostomy.

The purpose of this study is to evaluate the effectiveness of endoscopic dacryocystorhinostomy by the posterior lacrimal sac approach without use of lacrimal stents or harvest of mucosal flaps as a valid surgical procedure for the treatment of an obstruction of the lacrimal pathways. A retrospective evaluation was conducted in a cohort of 75 patients between 2007 and 2011. A total of 78 endoscopic dacryocystorhinostomies were analyzed in 75 patients. After a mean follow-up of 25.7 months (minimum 12 months), 93.3% had a complete relief of symptoms after surgery. Our experience appears to confirm that the endoscopic posterior lacrimal sac approach with no stent insertion or mucosal flaps creation is a good alternative to other known endoscopic procedures.

Adenoid hypetrophy: definition of some risk factors.

Adenoids removed for airway obstruction and-or recurrent infections have been studied to identify a possible mechanism to explain chronicity. In this regard, macrophages may play a relevant pathogenic role as well as neutrophils during bacterial infections and eosinophils in allergic inflammation. Therefore, this study aimed at investigating some mediators as surrogate markers of inflammation in children who had to undergo to adenoidectomy. Globally, 67 children (25 females, 42 males, mean age 4.9 years), affected by persistent obstruction caused by adenoid hypertrophy were consecutively enrolled into the study. Blood samples were collected from patients and controls to determine serum CD163, Myeloperoxidase (MPO) and ECP. There were significant differences between patients and controls for serum CD163 (p less than 0.0001); MPO (p less than 0.0001); serum ECP (p less than 0.0001). This study demonstrated some risk factors for severe AH: apnoea, recurrent respiratory infections, and high serum CD163 levels.

Nasal polyposis in children.

Nasal polyposis is a chronic inflammatory disease affecting the nasal cavity and the paranasal sinuses. It is a relatively common disease, occurring in 1-4 % of the general population, but it is rarely described in the pediatric population. Most of the published series include children presenting with other underlying systemic diseases, mainly cystic fibrosis. The aim of the present study was to describe the characteristics of the patients suffering from nasal polyposis, evaluated at the Pediatric Clinic of the University of Pavia (Italy) over the last 17 years. 56 consecutive pediatric patients referring to our Pediatric Department had a diagnosis of nasal poyposis over the last 17 years. All children underwent allergy evaluation, nasal endoscopy, CT scan of the paranasal sinus, and Functional Endoscopic Sinus Surgery. The mean age of the present cohort was of 11.8 years and most of the patients were male. 50% of the patients presented with unilateral, polyposis, mostly with a diagnosis of antrochoanal polyp. 4 patients presenting with bilateral polyposis suffered from cystic fibrosis. Main symptoms at diagnosis included nasal obstruction, snoring and rhinorrhea 32% of the patients presented at least a positivity to skin prick test, for major inhalant and food allergens. Nasal polyposis in children could represent an alert sign for other underlying systemic diseases. Nasal endoscopy should therefore be prescribed when a diagnosis is suspected. To properly treat a patient presenting with nasal polyposis, it is necessary to integrate medical and surgical skills through a multidisciplinary approach.

Adenoid assessment in paediatric patients: the role of flexible nasal endoscopy.

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80's, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size.

The evolution of the adenoidectomy: analysis of different power-assisted techniques.

Techniques and instruments for adenoidectomy have considerably changed over the years. With the introduction in Otolaryngology of power-assisted instruments for endoscopic sinus surgery, the classic adenoidectomy performed with curette or adenotome has evolved, with an improved patients' outcome and a better satisfaction of the surgeon. The purpose of this article is to describe and critically analyze the literature reports about different methods of power-assisted adenoidectomy. We performed a literature search (Medline) to identify all available reports. We discussed the surgical techniques and reviewed advantages and disadvantages of each method. The techniques can be schematically divided in non-endoscopic, usually performed with a laryngeal mirror, and endoscopic-assisted. The endoscopic control can be obtained either trans-nasally or trans-orally, as well as the microdebrider can be inserted in the nasal cavity or maneuvered through the oral cavity. Some authors reported the usage of the power-assisted instruments in performing the entire adenoidectomy; while, according with other authors, the microdebrider can be used as a step of the surgical procedure, for a combined adenoidectomy. In conclusion, all the methods seem to be safe and effective, and the personal experience of the surgeon should guide the choice of the instruments. However, we personally consider the endoscopic techniques as the most suitable, and among these the Transoral Endonasal-Controlled Combined Adenoidectomy (TECCA) should be considered as the most ergonomic technique to perform a power-assisted adenoidectomy.

Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven).

BACKGROUND: A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. METHODS: Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130-670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid) buffer; or by reducing temperature to 32 degrees C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. RESULTS: Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES. CONCLUSIONS: Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia.

Anesthesiological and intensive care considerations in children undergoing extensive cerebral excision procedure for congenital epileptogenic lesions.

INTRODUCTION: Epilepsy is a relatively common condition in childhood with a generally favorable prognosis of the affected population. Nevertheless, a significant minority of the treated children do not respond to the medical treatment so that surgical treatment is necessary. While minor surgical procedures have a negligible incidence of mortality, major ones may carry a significant risk of perioperative complications. The leading cause of mortality is represented by hemorrhagic derangements after high intraoperative and postoperative blood loss, mostly in very young patients. Therefore, restoration of euvolemia, detection and correction of related bleeding disorders represent the major concern for pediatric neuroanesthesiologists and intensivists throughout the perioperative period. The present report is focused on the anesthesia and intensive care management of the surgical epileptic patient. CONCLUSION: Authors recommend that these high-risk procedures should be performed in highly experienced centers where pediatric neurosurgery is performed daily.

Infectious diseases of childhood and their anesthetic implications.

In western world, infectious diseases in childhood have dramatically decreased in recent years. The first reason is related to the better socio-economic conditions but the highly efficiency of immunizations programs cannot be forgotten. Nevertheless children can be still exposed to infections, as vaccines are not able to completely protect all treated patients. Anesthesiologists should be aware of the basic mechanism of immunization as it is well known that anesthesia and surgery themselves reduce human immune response. In fact, nitrous oxide depresses bone marrow function, while halothane, nitrous oxide again and isoflurane reduce neutrophil biocidal activity. On the contrary, all the anesthesia techniques (peripheral anesthesia) which inhibit stress responses have beneficial effect on the immune system function. Not urgent procedures requiring anesthesia should be deferred for three weeks after vaccination when all the related symptoms will be over. Also important is the knowledge of the incubation period that is the time from contact with a person affected by the infectious illness until the onset of the typical disease. During these periods elective anesthesia must not be performed. On the other hand, if anesthesia is delivered, the patient's ability to react can be compromised and it is possible to have florid disease exacerbation including related complications.

Perioperative management of face-to-face craniopagus twins separation.

Craniopagus conjoining represents a complex and challenging issue for neurosurgeons as well as for anesthesiologists. A rare face-to-face case of conjoined twins underwent surgical separation and presented peculiar differences compared with those already reported in the literature. Even in cases lacking large cerebrovascular sinus connections, the impending risk of large blood loss and hemorrhagic shock in the infant requires a high level of surveillance and the institution of invasive monitoring.

Hemispherectomy procedures in children: haematological issues.

OBJECTS: In literature, excessive perioperative haemorrhage and related haemodynamic instability have been described as major risk factors in hemispherectomy. In this report we analyse the impact of neurosurgical operation on both the haematological and coagulative patterns of these children, especially focusing on younger patients. METHODS: From 1993 to 2003, 18 consecutive children suffering from intractable epilepsia and treated by hemispherectomy were admitted to the Pediatric Intensive Care Unit (PICU) of Catholic University Medical School, Policlinico Gemelli, Rome. Eight children had an entire hemisphere removed (anatomical hemispherectomy), whereas the remaining 10 underwent disconnective procedures (functional hemispherectomy) or cerebral cortex ablations (e.g. hemicorticectomy). Eleven out of these 18 children underwent hemispherectomy because of hemimegalencephaly (HME): their mean age was 14.5 months (range 3-56 months); non-HME patients underwent surgery for epileptogenic lesions involving the cerebral hemisphere to a great extent or diffusely. Data have been compared with an historical cohort of 13 children operated on before 1992 at the same institution comparable for age, aetiology of epilepsy and the modalities of surgical operation. CONCLUSIONS: Blood losses and haemotransfusions showed a profound influence on the haematologic/coagulative status of the children operated upon. A strict correlation was demonstrated between estimated red cell volume (ERCV) loss and haemostatic impairment in this series. Recent surgical techniques appear to reduce blood losses and related haemocoagulative risks even in younger patients.

[Anesthesia for neurosurgery in children: techniques and monitoring]. / Anestesia in neurochirurgia pediatrica: tecniche e monitoraggio.

Pediatric neuroanesthesia can be seen as a specific branch of anesthesia half way in between pediatric anesthesia and neuroanesthesia. As a matter of fact, we must keep well in mind the peculiarities of the pediatric patient and the different pharmadynamic and pharmacochinetic properties of the anesthetic drugs, particularly in neonates and infants. Other relevant problems are: 1) high complexity of surgical procedures implying a difficult anesthesiological management; 2) complex blood loss management either if we want to apply a blood sparing technique strategy or if we consider the problems related to diagnosis and treatment of coagulative disorders caused by intraoperative massive blood loss; 3) management of patients with latex allergy for the high incidence, in pediatric neuroanesthesia, of patients belonging to high risk groups; 4) need of repeated radiological examinations implying several anesthesiological procedures. In this article aspects related to the anesthesiological techniques and to the hemodynamic and neurophysiological monitoring of pediatric neurosurgical patients were also discussed.

Antimicrobial efficacy of external fixator pins coated with a lipid stabilized hydroxyapatite/chlorhexidine complex to prevent pin tract infection in a goat model.

BACKGROUND: Pin tract infection is a common complication of external fixation. An antiinfective external fixator pin might help to reduce the incidence of pin tract infection and improve pin fixation. METHODS: Stainless steel and titanium external fixator pins, with and without a lipid stabilized hydroxyapatite/chlorhexidine coating, were evaluated in a goat model. Two pins contaminated with an identifiable Staphylococcus aureus strain were inserted into each tibia of 12 goats. The pin sites were examined daily. On day 14, the animals were killed, and the pin tips cultured. Insertion and extraction torques were measured. RESULTS: Infection developed in 100% of uncoated pins, whereas coated pins demonstrated 4.2% infected, 12.5% colonized, and the remainder, 83.3%, had no growth (p < 0.01). Pin coating decreased the percent loss of fixation torque over uncoated pins (p = 0.04). CONCLUSION: These results demonstrate that the lipid stabilized hydroxyapatite/chlorhexidine coating was successful in decreasing infection and improving fixation of external fixator pins.