mRECIST criteria to assess recurrent thyroid carcinoma treatment response after radiofrequency ablation: a prospective study.

PURPOSE: Surgical removal is recommended for recurrent thyroid carcinomas (RTCs) unable to uptake radioiodine and/or not responsive to chemotherapy. However, repeated neck dissection is difficult for surgeons. Thus, radiofrequency ablation (RFA) was proposed for RTCs. The aim of this prospective study is to assess RTC treatment response after RFA, according to well-established criteria. METHODS: Sixteen lesions in 13 patients were treated by RFA. All patients refused/were excluded from repeated surgery or other conventional therapy. CT and US examinations were performed before RFA to evaluate lesion volume and vascularization. All RFA procedures were performed under US-guidance by an 18-gauge, electrode. Treatment response was evaluated by CT, according to RECIST 1.1 and to mRECIST guidelines; CT examinations were performed during follow-up (6-18 months); the volume of residual vital tumour tissue and the percentage of necrotic tissue were estimated by contrast enhanced CT. RESULTS: RFA was well tolerated by all patients; in two cases laryngeal nerve paralysis was observed. Mean pre-treatment volume was 4.18 ± 3.53 ml. Vital tumour tissue and percentage of necrosis at 6, 12 and 18 months were 0.18 ± 0.25, 0.11 ± 0.13, 0.29 ± 0.40 ml and 91.9 ± 11.1, 90.4 ± 13.3, 80.8 ± 23.1%. According to RECIST 1.1, target lesion response was classified as complete response (CR) in one case, partial response (PR) in 11/16, stable disease in 4/16 cases. According to mRECIST, 11/16 cases were classified as CR and the remaining 5 as PR. CONCLUSION: RFA is a safe procedure to treat the viable tumour tissue and to reduce the RTC volume; as to the criteria to assess treatment response, mRECIST appears to be more accurate.

Trace elements and diabetes: Assessment of levels in tears and serum.

Tear film is critical for the well-being and homeostasis of the ocular surface. Although the composition of the tear film is well known, the composition of metallic elements have yet to be analysed. Despite trace elements metabolism has been reported to play a role in the pathogenesis of diabetes mellitus, a metabolic disease that affects several aspects of homeostasis, little is known in the literature regarding concentration and possible variation of metallic elements in tear film. We studied the concentrations of several essential and non-essential metallic elements in the tear fluid and serum of patients with type II diabetes mellitus and a group of non-diabetic controls. Serum and tear fluid were collected from 97 patients: 47 type II diabetic patients and 50 non-diabetic controls. Regarding tear film, there were statistically significant differences in Zinc, Chrome, Cobalt, Manganese, Barium, and Lead between groups; the values of all metallic elements were found to be statistically significant higher in patients with mellitus type II diabetes. Regarding serum values there was a statistically significant difference in Chrome, Cobalt, and Selenium values; the concentrations of Chrome and Cobalt were higher in the control group, while Selenium concentration was higher in diabetic patients. In patients with type II diabetes, metal elements with higher concentrations in tears compared to serum were: Lead, Barium, Manganese, Cobalt, and Chrome. In the control group, the metal elements with the highest concentration in tear film compared to serum were Chrome, Manganese, Barium, and Lead. In this study, we attempted to evaluate the possible effect of a disease, such as diabetes, on the metabolism of metallic elements. Although our evidence was very interesting, it is probably limited in its accuracy due to the fact that individuals in the control group harboured ocular pathologies. This work lays the foundation for future studies.

Radiological predictors of final infarct volume in patients with proximal vascular occlusion.

INTRODUCTION: Various clinical and radiologic variables impact the neurologic prognosis of patients with ischemic cerebrovascular accidents. About 30% of ischemic cerebrovascular accidents are caused by proximal obstruction of the anterior circulation; in these cases, systemic thrombolysis is of limited usefulness. CT angiography is indicated in candidates for endovascular treatment. Various radiologic factors, including the grade of leptomeningeal collateral circulation, as well as the length, density, and extension of the thrombus, have been identified as predictors of neurologic prognosis after anterior ischemic cerebrovascular accidents due to proximal vascular obstruction. Final infarct volume correlations with mortality and long-term functional outcome in these patients. This study aimed to determine the best predictors of final infarct volume on CT angiography in patients with ischemic cerebral accidents due to proximal occlusion. MATERIALS AND METHODS: This retrospective observational study included adults with ischemic cerebrovascular accidents due to obstruction of the anterior circulation diagnosed by CT angiography in the period comprising June 2009 through December 2019. We measured the length and density of the thrombus in unenhanced CT images, and we used the clot burden score to record the grade of leptomeningeal collateral circulation and the extension of the thrombus. Then we measured the final infarct volume on follow-up CT and analyzed the correlations among these radiologic factors in the infarct volume. RESULTS: We included 54 patients [mean age, 82 y; 41 (75%) women] with ischemic cerebrovascular accidents due to proximal occlusion. About 60% of the cerebrovascular accidents affected the right cerebral hemisphere, and the most commonly affected vessel was the M1 segment of the medial cerebral artery (40.7%). Final infarct volume correlated with the grade of leptomeningeal collateral circulation (p=0.03) and with the clot burden score (p=0.01). Neither the length nor the density of the thrombus correlated with final infarct volume. CONCLUSION: The final infarct volume can be estimated on the initial CT angiogram. Nevertheless, we found no useful predictive factors in unenhanced CT images. The best independent radiologic predictors of the final infarct volume are the grade of collateral circulation and the clot burden score, especially in patients who did not undergo mechanical thrombectomy, because mechanical thrombectomy improves outcomes. These factors are important for decision making in the management of patients with ischemic cerebrovascular accidents due to proximal occlusion.

General practitioners' management of symptomatic uncomplicated diverticular disease of the colon by using rifaximin, a non-adsorbable antibiotic.

OBJECTIVE: Symptomatic uncomplicated diverticular disease of the colon (SUDD) is generally managed by gastroenterologists rather than General Practitioners (GPs). The aim of this study was to assess the efficacy of the treatment of SUDD with rifaximin, a non-absorbable antibiotic, in a primary care setting by GPs. PATIENTS AND METHODS: This retrospective, observational study investigated the use of rifaximin at a dose of 400 mg b.i.d. for 5, 7 or 10 days monthly, up to 3 months. The symptoms were reported by the patients using a visual analogic scale (VAS) of 0-10. RESULTS: 286 SUDD patients were enrolled (44.4% of men, average age 70.92±10.98). Respectively, 15 (5.2%) patients received the treatment for 5 days, 205 (71.7%) for 7 days and 66 (23.1%) for 10 days. After three months, a significant reduction of VAS score was observed in almost all symptoms assessed: 135 (47.2%) patients reported no abdominal pain (p<0.001) and 23 (8.1%) reported no symptom. Adverse events related to the treatment were recorded in 3 (1.04%) patients, all of them mild and not requiring interruption of the treatment. Acute diverticulitis occurred in 9 (3.1%) patients, but only 2 of them [0.7% (n=2)] underwent surgery due to complicated diverticulitis. Analysis within the different treatment groups (5, 7 and 10 days) shows that rifaximin treatment is effective in reducing the severity of symptoms in almost all groups except for the constipation in the 5-day group. CONCLUSIONS: Rifaximin can be effectively used by GPs in real-life for the management of SUDD.

Outcome of classical (CVPTC) and follicular (FVPTC) variants of papillary thyroid cancer: 15 years of follow-up.

PURPOSE: To compare the epidemiological, clinical, and pathological features of follicular (FVPTC) and classical (CVPTC) variants of papillary thyroid cancer and to correlate their outcomes according to different features. METHODS: Retrospective analysis of FVPTC and CVPTC patients selected at the moment of surgical treatment from 1999 to 2004, with a median follow-up of 15 years. RESULTS: Several significant differences were found between FVPTC and CVPTC such as the mean age at diagnosis, the presence of tumor capsule, the presence of thyroid capsule invasion, the presence of perithyroid soft tissue invasion, the lymph node metastases, the multifocality and bilaterality. At the end of follow-up only 9% (77/879) patients were not cured. However, a statistically significant lower percentage of persistent disease was found in the FVPTC than in the CVPTC group (3% vs. 14.5%, respectively, p < 0.0001). In multivariate analysis, the absence of the tumor capsule (OR = 6.75) or its invasion (OR = 7.89), the tumor size ≥4 cm (OR = 4.29), the variant CVPTC (OR = 3.35), and the presence of lymph node metastases (OR = 3.16) were all independent risk factors for the persistence of the disease. CONCLUSIONS: Despite an overall excellent prognosis of both variants, a higher percentage of CVPTC than FVPTC patients had a persistent disease. The absence of tumor capsule or its invasion, the tumor size ≥4 cm and the presence of lymph node metastases are other prognostic factors for the persistence of the disease. In contrast, the presence of an intact tumor capsule is the only good prognostic factor for their outcome.

Severe acute multineuropathy in Churg-Strauss syndrome in a patient with a history of melanoma.

We describe the clinicopathologic features of a 69-year-old man affected with acute onset Churg-Strauss syndrome with major peripheral nerve involvement. At admission the patient presented a one-week history of distal upper-limb asymmetrical paresthesias. Asthma had been present since the age of 55 and treated with leukotriene receptor antagonists (LTAs, Montelukast) for a few years. Multiple pulmonary infiltrates had been diagnosed during follow-up for melanoma. During hospitalization he showed rapidly progressive weakness worsening within a few hours; cerebrospinal fluid analysis, cervical MRI, head CT scan, nerve conduction studies and peripheral nerve and skeletal muscle biopsies were performed. Blood analysis showed leukocytosis and marked eosinophilia; p-ANCA were positive. Sural nerve biopsy showed a marked loss of myelinated fibers, thrombosed vessels surrounded by mononuclear and eosinophilic cells, necrotizing and hyaline degeneration. Eosinophilic infiltrates were shown in May-Grunwald-Giemsa stained sections. The eosinophils mostly occupied the outer zone of the adventitia at the margin of the active lesion. Perivascular cellular infiltrates within the epineurium were immunoreactive for T-lymphocytes and macrophages. Strong HLA-DR immunostaining was present in the perineurium and membrane attack complex deposition was present in a few endoneurial capillaries. Muscle biopsy showed neurogenic changes and one vessel surrounded by mononuclear cells. After a few days of corticosteroid therapy leukocytosis and eosinophilia normalized and the patient's clinical features stabilized.

Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma.

AIMS: Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. METHODS: MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. STAKEHOLDERS: Include patients, health care professionals (pharmacists and physicians), authorities, patient's associations, private and public sectors. RESULTS: MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU GRANTS 2018: MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). LESSONS LEARNT: (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

A frame-based representation for a bedside ventilator weaning protocol.

We describe the use of a frame-based knowledge representation to construct an adequately-explicit bedside clinical decision support application for ventilator weaning. The application consists of a data entry form, a knowledge base, an inference engine, and a patient database. The knowledge base contains database queries, a data dictionary, and decision frames. A frame consists of a title, a list of findings necessary to make a decision or carry out an action, and a logic or mathematical statement to determine its output. Frames for knowledge representation are advantageous because they can be created, visualized, and conceptualized as self-contained entities that correspond to accepted medical constructs. They facilitate knowledge engineering and provide understandable explanations of protocol outputs for clinicians. Our frames are elements of a hierarchical decision process. In addition to running diagnostic and therapeutic logic, frames can run database queries, make changes to the user interface, and modify computer variables.

Increased risk of nonalcoholic fatty liver disease in patients with coeliac disease on a gluten-free diet: beyond traditional metabolic factors.

BACKGROUND: A gluten-free diet (GFD) is known to be associated with altered macronutrient intake and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the hepatic hallmark of metabolic syndrome. The risk of NAFLD in patients with coeliac disease (CD) adhering to a GFD remains to be fully investigated; in particular, data from real-life clinical settings are lacking. AIM: To assess the prevalence and relative risk of NAFLD in CD patients treated with a GFD. METHODS: Case-control study, with prospective enrolment of CD outpatients following a GFD and controls. Patients were matched for demographic characteristics (age and gender) and metabolic risk factors (overweight, diabetes mellitus, total cholesterol, and triglycerides) using a 1:1 ratio. NAFLD was diagnosed according to the European Association for the Study of the Liver criteria. RESULTS: 202 CD patients and 202 controls were compared. The raw prevalence of NAFLD was 34.7% and 21.8% in the CD and control group, respectively (P = 0.006). Binary logistic regression confirmed an increased risk of NAFLD in the CD group (adjusted odds ratio = 2.90, 95% confidence interval: 1.64-5.15, P < 0.001). Additionally, the relative risk for NAFLD was notably higher in non-overweight CD patients (adjusted odds ratio = 5.71, 95% confidence interval: 2.30-14.19, P < 0.001). CONCLUSIONS: More than one-third of CD patients adhering to a GFD had concurrent NAFLD, accounting for a three-fold increased risk compared to the general population. Dietary advice provided using a patient-tailored approach should assist CD patients with NAFLD in achieving an appropriate nutritional intake whilst reducing the risk of long-term liver-related events.

MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence.

mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

Synthesis and biophysical characterization of G-rich oligonucleotides conjugated with sugar-phosphate tails.

A number of 5'-and 3'-glycoconjugates of the oligonucleotide (5')d(TGGGAG)(3') have been synthesized, exploiting fully automated, online phosphoramidite-based solid phase strategy, as potential anti-HIV-1 agents. The thermodynamic stability of the resulting quadruplexes has been investigated by thermal denaturation studies, via a detailed CD Q1 analysis.

Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family.

Adult Polyglucosan Body Disease (APBD) is a rare inherited leukodystrophy associated with axonal polyneuropathy, mainly reported in persons of Ashkenazi-Jewish descent. We describe three Italian siblings at disease onset, presenting in their fifties with a combination of pyramidal and ataxic signs, mild demyelinating neuropathy on neurophysiological investigation (1/3 cases) and transient symptoms (1/3). A leucoencephalopathy with infratentorial lesions without enhancement and medullary/spine atrophy was demonstrated on brain/spine MRI (3/3). Muscle biopsy was normal in 2/3; both muscle and nerve biopsy showed polyglucosan bodies in the sibling with polyneuropathy. This indicated a need for GBE1 sequencing, which revealed a novel missense mutation (c.1064G>A; p.Arg355His) and one previously described (c.1604A>G; p.Tyr535Cys) in all siblings. We highlight that peripheral neuropathy, deemed as disease hallmark, may be missing and that transient symptoms are confirmed as early disease manifestations. The pattern of damage at neuro-imaging described recurs irrespective of clinical presentation, constituting a unifying diagnostic clue.

A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family.

Autosomal dominant progressive external ophthalmoplegia (adPEO) is caused by mutations in at least three different genes: ANT1 (chromosome 4q34-35), TWINKLE, and POLG. The ANT1 gene encodes the adenine nucleotide translocator-1 (ANT1). We identified a heterozygous T293C mutation of the ANT1 gene in a Greek family with adPEO. The resulting leucine to proline substitution likely modifies the secondary structure of the ANT1 protein. ANT1 gene mutations may account for adPEO in families with different ethnic backgrounds.

Lack of apoptosis in mitochondrial encephalomyopathies.

BACKGROUND/OBJECTIVE: Apoptosis, or programmed cell death, is an evolutionary conserved mechanism essential for morphogenesis and tissue homeostasis, but it plays an important role also in pathologic conditions, including neurologic disorders. Its execution pathway is critically regulated at the mitochondrial level. Evidence of apoptosis in muscle specimens was investigated in patients with genetically defined mitochondrial encephalomyopathies. METHODS: Thirty-three muscle biopsies from patients with genotypically different mitochondrial diseases (single and multiple deletions, A3243G/A8344G point mutations of the mitochondrial DNA) were studied. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction was used as a marker of nuclear DNA fragmentation, as well as antibodies against pro- (Fas) or anti- (Bcl-2) apoptotic factors. Also, because one hallmark of apoptosis is morphologic, ultrastructural studies were performed on skeletal muscle from 18 of 33 patients, examining both phenotypically normal and ragged red fibers. RESULTS: In all muscle biopsies, no significant expression of either pro (Fas) and inhibiting (Bcl-2) apoptosis-related proteins was found, nor TUNEL positivity. This latter finding is confirmed by lack of morphologic evidence of apoptosis in all the fibers examined at the ultrastructural level. CONCLUSION: The authors' findings suggest that genetically determined defects of oxidative phosphorylation do not induce the apoptotic process and that apoptosis is not involved in the pathogenesis of mitochondrial disorders.

Partial depletion and multiple deletions of muscle mtDNA in familial MNGIE syndrome.

OBJECTIVE: To describe the unique combination of partial depletion and multiple deletions of mitochondrial DNA (mtDNA) on muscle DNA analysis of three siblings with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). BACKGROUND: MNGIE is a relatively homogeneous autosomal recessive disorder characterized by gastrointestinal dysmobility, ophthalmoparesis, peripheral neuropathy, mitochondrial myopathy, and altered white matter signal at brain imaging. Muscle multiple mtDNA deletions have been found in about half of the described cases. METHODS: We studied three affected siblings (two were monozygotic twins) born to nonconsanguineous parents. Muscle mtDNA was investigated by quantitative Southern and Slot blot techniques and by PCR analysis. Morphologic confirmation in the muscle tissue was achieved by using in situ hybridization with a mtDNA probe complementary to an undeleted region and by DNA immunohistochemistry. RESULTS: All three patients showed ragged red (RRF) and cytochrome c oxidase-negative fibers, as well as partial deficiency of complexes I and IV. Southern and Slot blot analyses showed mtDNA depletion in all patients. Multiple mtDNA deletions were also detected by PCR analysis. In situ hybridization demonstrated an overall signal weaker than controls, with a relatively higher signal in RRF. Antibodies against DNA showed a decreased cytoplasmic network. CONCLUSIONS: The muscle histopathology and respiratory chain enzyme defects may be accounted for by the decreased mtDNA amount and by the presence of mtDNA deleted molecules; however, relative levels of mtDNA seem to correlate with life span in these patients. The combination of partial depletion and multiple deletions of mtDNA might indicate the derangement of a common genetic mechanism controlling mtDNA copy number and integrity.

Immunoreactive localization of vasoactive hormones (atrial natriuretic peptide and endothelin) in the heart of Protopterus annectens, an African lungfish

The present study demonstrated, by immunohistochemistry and Western blotting, the presence of immunoreacting atrial natriuretic peptide (ANP) and endothelin in the heart of Protopterus annectens by both light and electron microscopy. The distribution of ANP granules was investigated. ANP granules were localised in myocytes from the atrium, ventricle and conus arteriosus; endothelin-1 (ET-1) was demonstrated in subendocardial myocytes of the atrium and the conus. No ET-1 immunoreactivity was observed in the ventricle wall. At the light-microscopical level, ET-1 appeared to occur in the endocardium, but at the electron-microscopical level no immunogold labelling was seen on the granules of the endocardial cells. It is suggested that ET-1 is produced and stored in the subendocardial cells and released into the subendocardial space to reach the ANP-producing myocytes and the endothelial cells.

Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation.

Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80% of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defects. Abnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow "protected" against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling.

Hydrolysis of oleuropein by recombinant beta-glycosidase from hyperthermophilic archaeon Sulfolobus solfataricus immobilised on chitosan matrix.

The recombinant beta-glycosidase (EcS beta gly) from Sulfolobus solfataricus was immobilised on chitosan to perform the enzymatic hydrolysis of commercial oleuropein (heterosidic ester of elenolic acid and 3,4-dihydroxy-phenylethanol (hydroxytyrosol)) at two temperatures (60 and 70 degrees C). Interestingly, on the basis of the reasonable assumption that the enzyme hydrolyses only the sugar linkage, the biotransformation produces unstable aglycone species formed by oleuropein hydrolysis that, differently from some commercially available beta-glucosidases tested, give rise to the formation of hydroxytyrosol, at the operative temperatures of the bioreactor. The results of the biotransformation at 70 degrees C showed that the main products are hydroxytyrosol, and glucose, being the oleuropein aglycone present in low amount at the end of reaction. Both in single step approach or in recycle approach the amounts of glucose and oleuropein aglycone were lightly dependent from flow rate. The amount of hydroxytyrosol, increased on decreasing the flow rate of bioreactor in recycle approach, following a non-linear trend and obtaining the highest value at a flow rate of 15 ml h-1 while in the single step approach the 3,4-dihydroxy-phenylethanol was at its maximum at higher flow rate (16 ml h-1). For the hydrolysis of the oleuropein by bioreactor at 60 degrees C we used lower molar ratio oleuropein/enzyme only by the single step approach. In these conditions it is possible to obtain high amounts of only two products (glucose and hydroxytyrosol) in short time (2 h). The stability of the bioreactor at the operative temperatures showed a t1/2 of 30 days at 70 degrees C and a t1/2 of 56 days at 60 degrees C.

Airway pressure release ventilation in pediatrics.

OBJECTIVES: The purpose of this study was to determine the effectiveness of airway pressure release ventilation in children. DESIGN: Prospective, randomized, crossover clinical trial. SETTING: This study was conducted in our 33-bed pediatric intensive care unit at The Children's Hospital of Philadelphia. PATIENTS: Patients requiring mechanical ventilatory support and weighing >8 kg were considered for enrollment. Patients were excluded if they required mechanical ventilatory support for >7 days or required >.50 Fio(2) for >7 days before enrollment. Patients with documented obstructive airway disease and congenital or acquired heart disease were excluded as well. INTERVENTIONS: Each patient received both volume-controlled synchronized intermittent mechanical ventilation (SIMV) and airway pressure release ventilation (APRV) via the Drager Evita ventilator (Drager, Lubeck, Germany). Measurements were obtained after the patient was stabilized on each ventilation mode. Stabilization was defined as oxygenation, ventilation, hemodynamic variables, and patient comfort within the acceptable range for each patient as determined by the bedside physician. After measurements were obtained on the initial mode of ventilation, the subjects crossed over to the alternative study mode. Stabilization was again achieved, and measurements were repeated. After completion of the second study measurements, patients were placed on the ventilation modality preferred by the bedside clinician and were followed through weaning and extubation. Measurements: Vital signs, airway pressures, minute ventilation, Spo(2), and E(T)CO(2) were recorded at enrollment and at each study condition. MAIN RESULTS: APRV provided similar ventilation, oxygenation, mean airway pressure, hemodynamics, and patient comfort as SIMV. Inspiratory airway pressures were lower with APRV when compared with SIMV. CONCLUSIONS: Using APRV in children with mild to moderate lung disease resulted in comparable levels of ventilation and oxygenation at significantly lower inspiratory peak and plateau pressures. Based on these findings, we plan to evaluate APRV in children with significant lung disease.

Weaning children from mechanical ventilation: a prospective randomized trial of protocol-directed versus physician-directed weaning.

OBJECTIVE: Compare outcomes between physician-directed and protocol-directed weaning from mechanical ventilation in pediatric patients. DESIGN: Prospective-randomized. SETTING: Pediatric and cardiac intensive care units in a 307-bed tertiary referral hospital for children. INTERVENTIONS: The control group (physician-directed) was weaned according to individual physician order for reduction in minute ventilation, positive end-expiratory pressure, and ordered oxygen saturation parameters for reduction in fraction of inspired oxygen (F(IO)(2)). The study group (protocol-directed) was weaned according to a predetermined algorithm developed for the purpose of this investigation. METHODS: The study enrolled 223 patients (116 physician-directed, 107 protocol-directed). All patients were monitored for hemodynamics, ventilator parameters, arterial blood gas values when available, oxygen saturation, weaning time, pre-weaning time, extubation time, and time on F(IO)(2) > or = 0.40. We also monitored the incidence of reintubation, subglottic stenosis, tracheitis, and pneumonia. The protocol-directed group had additional measurements of actual versus predicted minute volume, comparisons of respiratory rate (actual versus predicted for age), and presence of spontaneous breathing effort for 10 consecutive minutes. Data analysis was done according to intent to treat. RESULTS: There was no significant difference in 12-hour and 24-hour pediatric risk of mortality (PRISM III) scores between groups. The protocol-directed group overall had shorter total ventilation time, weaning time, pre-weaning time, time to extubation, and time on F(IO)(2) >0.40, although after stratification for respiratory diagnosis, only the difference in weaning time remained significant. There was no difference in the incidence of reintubation, new-onset tracheitis, subglottic stenosis, or pneumonia. CONCLUSIONS: Protocol-directed weaning resulted in a shorter weaning time than physician-directed weaning in these pediatric patients.