Relationship between sex and clinical and imaging features of early axial spondyloarthritis: results from a 48 month follow-up (Italian arm of the SPondyloArthritis Caught Early (SPACE) study).

OBJECTIVES: To assess the association between sex and clinical and disease activity indices, and X-rays and magnetic resonance imaging (MRI) features, in early-stage axial spondyloarthritis (axSpA). METHOD: Baseline data analysis was conducted on the Italian SPACE cohort, including patients with chronic back pain (duration ≥ 3 months and ≤ 2 years; onset < 45 years). Patients underwent MRI and X-rays of the sacroiliac joints (SIJs) to establish the diagnosis of axSpA, according to Assessment of SpondyloArthritis international Society criteria and physician's judgement. Clinical features, disease activity and functional indices, and images were collected at baseline and yearly during 48 months. Spinal and SIJ X-rays and MRI images were scored by two readers following Spondyloarthritis Research Consortium of Canada (SPARCC), modified Stoke Ankylosing Spondylitis Spinal Score, and modified New York criteria. Characteristics of axSpA patients according to sex (male/female) were compared over time using descriptive statistics. RESULTS: Ninety-one patients had axSpA (83.5% non-radiographic; 16.5% radiographic); 47.3% were male. Males were younger, with shorter duration of axial symptoms, and more frequently had HLA-B27 positivity, radiographic sacroiliitis with a bilateral/symmetric pattern, and more signs of spondylitis. Females more frequently showed peripheral/entheseal involvement and the non-radiographic phenotype. Males showed increased pelvic/spinal radiographic progression and more often had active sacroiliitis on MRI. Although the frequency of inflammatory corner lesions did not differ between males and females, localization varied, with more cervical/thoracic MRI-spine lesions in females and more lumbar lesions in males. We observed a significant downward trend of SPARCC SIJ/spine scores in all patients, irrespective of sex. More fat lesions were observed on MRI-spine in females and on MRI-SIJ in males. CONCLUSION: Sex was associated with distinct axSpA features: females showed low-grade radiographic sacroiliitis and spinal progression, and a higher prevalence of cervical and thoracic spine MRI signs.

Management of late-onset fetal growth restriction: pragmatic approach.

OBJECTIVES: There is limited prospective evidence to guide the management of late-onset fetal growth restriction (FGR) and its differentiation from small-for-gestational age. The aim of this study was to assess prospectively a novel protocol in which ultrasound criteria were used to classify women with suspected late FGR into two groups: those at low risk, who were managed expectantly until the anticipated date of delivery, and those at high risk, who were delivered soon after 37 weeks of gestation. We also compared the outcome of this prospective cohort with that of a historical cohort of women presenting similarly with suspected late FGR, in order to evaluate the impact of the new protocol. METHODS: This was a prospective study of women with a non-anomalous singleton pregnancy at ≥ 32 weeks' gestation attending a tertiary hospital in London, UK, between February 2018 and September 2019, with estimated fetal weight (EFW) ≤ 10th centile, or EFW > 10th centile in addition to a decrease in fetal abdominal circumference of ≥ 50 centiles compared with a previous scan, umbilical artery Doppler pulsatility index > 95th centile or cerebroplacental ratio < 5th centile. Women were classified as low or high risk based on ultrasound and Doppler criteria. Women in the low-risk group were delivered by 41 weeks of gestation, unless they subsequently met high-risk criteria, whereas women in the high-risk group (EFW < 3rd centile, umbilical artery Doppler pulsatility index > 95th centile or EFW between 3rd and 10th centiles (inclusive) with abdominal circumference drop or abnormal Dopplers) were delivered at or soon after 37 weeks. The primary outcome was adverse neonatal outcome and included hypothermia, hypoglycemia, neonatal unit admission, jaundice requiring treatment, suspected infection, feeding difficulties, 1-min Apgar score < 7, hospital readmission and any severe adverse neonatal outcome (perinatal death, resuscitation using inotropes or mechanical ventilation, 5-min Apgar score < 7, metabolic acidosis, sepsis, and cerebral, cardiac or respiratory morbidity). Secondary outcomes were adverse maternal outcome (operative delivery for abnormal fetal heart rate) and severe adverse neonatal outcome. Women managed according to the new protocol were compared with a historical cohort of 323 women delivered prior to the implementation of the new protocol, for whom management was guided by individual clinician expertise. RESULTS: Over 18 months, 321 women were recruited to the prospective cohort, of whom 156 were classified as low risk and 165 were high risk. Adverse neonatal outcome was significantly less common in the low-risk compared with the high-risk group (45% vs 58%; adjusted odds ratio (aOR), 0.6 (95% CI, 0.4-0.9); P = 0.022). There was no significant difference in the rate of adverse maternal outcome (18% vs 24%; aOR, 0.7 (95% CI, 0.4-1.2); P = 0.142) or severe adverse neonatal outcome (3.8% vs 8.5%; aOR, 0.5 (95% CI, 0.2-1.3); P = 0.153) between the low- and high-risk groups. Compared with women in the historical cohort classified retrospectively as low risk, low-risk women managed under the new protocol had a lower rate of adverse neonatal outcome (45% vs 58%; aOR, 0.6 (95% CI, 0.4-0.9); P = 0.026). CONCLUSIONS: Appropriate risk stratification to guide management of late FGR was associated with a reduced rate of adverse neonatal outcome in low-risk pregnancies. In clinical practice, a policy of expectantly managing women with a low-risk late-onset FGR pregnancy at term could improve neonatal and long-term development. Randomized controlled trials are needed to assess the effect of an evidence-based conservative management protocol for late FGR on perinatal morbidity and mortality and long-term neurodevelopment. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Water quality and human health: A simple monitoring model of toxic cyanobacteria growth in highly variable Mediterranean hot dry environments.

Due to population growth, urbanization and economic development, demand for freshwater in urban areas is increasing throughout Europe. At the same time, climate change, eutrophication and pollution are affecting the availability of water supplies. Sicily, a big island in southern Italy, suffers from an increasing drought and consequently water shortage. In the last decades, in Sicilian freshwater reservoirs several Microcystis aeruginosa and more recently Planktothrix rubescens blooms were reported. The aims of the study were: (1) identify and quantify the occurring species of cyanobacteria (CB), (2) identify which parameters, among those investigated in the waters, could favor their growth, (3) set up a model to identify reservoirs that need continuous monitoring due to the presences, current or prospected, of cyanobacterial blooms and of microcystins, relevant for environmental and, consequentially, for human health. Fifteen artificial reservoirs among the large set of Sicilian artificial water bodies were selected and examined for physicochemical and microbiological characterization. Additional parameters were assessed, including the presence, identification and count of the cyanobacterial occurring species, the measurement of microcystins (MCs) levels and the search for the genes responsible for the toxins production. Principal Component Analysis (PCA) was used to relate environmental condition to cyanobacterial growth. Water quality was poor for very few parameters, suggesting common anthropic pressures, and PCA highlighted clusters of reservoirs vulnerable to hydrological conditions, related to semi-arid Mediterranean climate and to the use of the reservoir. In summer, bloom was detected in only one reservoir and different species was highlighted among the Cyanobacteria community. The only toxins detected were microcystins, although always well below the WHO reference value for drinking waters (1.0 µg/L). However, molecular analysis could not show the presence of potential cyanotoxins producers since a few numbers of cells among total could be sufficient to produce these low MCs levels but not enough high to be proved by the traditional molecular method applied. A simple environmental risk-based model, which accounts for the high variability of both cyanobacteria growth and cyanotoxins producing, is proposed as a cost-effective tool to evaluate the need for monitoring activities in reservoirs aimed to guarantee supplying waters safety.

Impact of the environment on the health: From theory to practice.

The Erice 56 Charter titled "Impact of the environment on the health: from theory to practice" was unanimously approved at the end of the 56th course of the "International School of Epidemiology and Preventive Medicine G. D'Alessandro" held from 3rd to November 7, 2019 in Erice - Sicily (Italy) and promoted by the Study Group of "Environment and Health" of the Italian Society of Hygiene, Preventive Medicine and Public Health. The course, that included lectures, open discussions and guided working groups, was aimed to provide a general training on epidemiological and toxicological aspects of the environmental health impact, to be used by public health professionals for risk assessment, without forgetting the risk communications. At the end of the course 12 key points were agreed among teachers and students: they underlined the need of specific training and research, in the perspective of "One Health" and "Global Health", also facing emerging scientific and methodological issues and focusing on communication towards stakeholders. This Discussion highlight the need to improve knowledge of Health and Environment topic in all sectors of health and environmental prevention and management.

The challenge of maintaining necessary vascular and endovascular services at a referral center in Northern Italy during the COVID-19 outbreak.

OBJECTIVES: The Padova Hospital Vascular Surgery Division is located in Veneto, one of the area of the Northern Italy most hit by the Coronavirus disease 2019 outbreak. The aim of this paper is to describe the protocols adopted and to evaluate their impact during the acute phase of Coronavirus spread, focusing on the management of elective and urgent/emergent surgery, outpatients activity, and also health staff preservation from intra-hospital Coronavirus disease 2019 infection. METHODS: Several measures were progressively adopted in the Padova University Hospital to front the Coronavirus disease 2019 outbreak, with a clear strong asset established by 9 March 2020, after the Northern Italy lockdown. Since this date, the Vascular Surgery Unit started a "scaled-down" activity, both for elective surgical procedures and for the outpatient Clinical activities; different protocols were developed for health preservation of staff and patients. We compared a two months period, 30 days before and 30 days after this time point. In particular, emergent vascular surgery was regularly guaranteed as well as urgent surgery (to be performed within 24 h). Elective cases were scheduled for "non-deferrable" pathology. A swab test protocol for COVID-19 was applied to health-care professionals and hospitalized patients. RESULTS: The number of urgent or emergent aortic cases remained stable during the two months period, while the number of Hospital admissions via Emergency Room related to critical limb ischemia decreased after national lockdown by about 20%. Elective vascular surgery was scaled down by 50% starting from 9 March; 35% of scheduled elective cases refused hospitalization during the lockdown period and 20% of those contacted for hospitalization where postponed due to fever, respiratory symptoms, or close contacts with Coronavirus disease 2019 suspected cases. Elective surgery reduction did not negatively influence overall carotid or aortic outcomes, while we reported a higher major limb amputation rate for critical limb ischemia (about 10%, compared to 4% for the standard practice period). We found that 4 out of 98 (4%) health-care providers on the floor had an asymptomatic positive swab test. Among 22 vascular doctors, 3 had a confirmed Coronavirus disease 2019 infection (asymptomatic); a total of 72 swab were performed (mean = 3.4 swab/person/month) during this period; no cases of severe Coronavirus disease 2019 (deaths or requiring intensive care treatment) infection were reported within this period for the staff or hospitalized patients. CONCLUSIONS: Elective vascular surgery needs to be guaranteed as possible during Coronavirus disease 2019 outbreak. The number of truly emergent cases did not reduce, on the other side, Emergency Room accesses for non-emergent cases decreased. Our preliminary results seem to describe a scenario where, if the curve of the outbreak in the regional population is flattened, in association with appropriate hospitals containment rules, it may be possible to continue the activity of the Vascular Surgery Units and guarantee the minimal standard of care.

Subclinical TRAPS treated with canakinumab.

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease characterized by recurrent episodes of fever and systemic inflammation. We describe the case of a 19-year-old patient who was referred to our attention with frequent subclinical TRAPS episodes characterized by mild arthralgias and crampy abdominal pain, without fever. Inflammatory markers, including serum amyloid A which increases the risk of long-term amyloidosis, were persistently high also when the patient was in good general conditions. Therapy with human anti-interleukin 1ß monoclonal antibody, canakinumab, led to disease control and normalization of the inflammatory markers, which are currently still normal. This clinical case supports the need to treat also subclinical TRAPS. In this respect, canakinumab is effective and reduces the risk of developing amyloidosis.

Kawasaki disease and cardiac involvement: an update on the state of the art.

Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. It has a self-limiting course and so far, represents the most common cause of coronary heart disease acquired in children aged between 6 months and 5 years. The inflammatory process can involve the coronary arteries with the formation of aneurysms and thrombotic occlusions with the risk of sudden death, especially in infants. Myocardial inflammation and abnormalities of cardiac contractility can occur acutely or many years after the disease onset. Therapy must be started within 10 days after the onset of symptoms to reduce the risk of heart complications. Immunoglobulin and aspirin treatment are effective in reducing heart complications. Recent studies have shown new therapeutic strategies (corticosteroids, immunosuppressive and biological drugs) in case of ineffectiveness of treatment with immunoglobulins.

Lipid Peroxidation and Antioxidant Consumption as Early Markers of Neurosurgery-Related Brain Injury in Children.

BACKGROUND AND AIMS: Lipid peroxidation represents a marker of secondary brain injury both in traumatic and in non-traumatic conditions-as in major neurosurgical procedures-eventually leading to brain edema amplification and further brain damage. Malondialdehyde (MDA), a lipid peroxidation marker, and ascorbate, a marker of antioxidant status, can represent early indicators of this process within the cerebrospinal fluid (CSF). We hypothesized that changes in cerebral lipid peroxidation can be measured ex vivo following neurosurgery in children. METHODS: Thirty-six children (M:F = 19/17, median age 32.9 months; IQR 17.6-74.6) undergoing neurosurgery for brain tumor removal were admitted to the pediatric intensive care unit (PICU) in the postoperative period with an indwelling intraventricular catheter for intracranial pressure monitoring and CSF drainage. Plasma and CSF samples were obtained for serial measurement of MDA, ascorbate, and cytokines. RESULTS: An early brain-limited increase in lipid peroxidation was measured, with a significant increase from baseline of MDA in CSF (p = 0.007) but not in plasma. In parallel, ascorbate in CSF decreased (p = 0.05). Systemic inflammatory response following brain surgery was evidenced by plasma IL-6/IL-8 increase (p 0.0022 and 0.0106, respectively). No correlation was found between oxidative response and tumor site or histology (according to World Health Organization grading). Similarly, lipid peroxidation was unrelated to the length of surgery (mean 321 ± 73 min), or intraoperative blood loss (mean 20.9 ± 16.8% of preoperative volemia, 44% given hemotransfusions). Median PICU stay was 3.5 days (IQL range 2-5.5 d.), and postoperative ventilation need was 24 h (IQL range 20-61.5 h). The elevation in postoperative MDA in CSF compared with preoperative values correlated significantly with postoperative ventilation need (P = 0.05, r2 0168), while no difference in PICU stay was recorded. CONCLUSIONS: Our results indicate that lipid peroxidation increases consistently following brain surgery, and it is accompanied by a decrease in antioxidant defences; intraventricular catheterization offers a unique chance of oxidative process monitoring. Further studies are needed to evaluate whether monitoring post-neurosurgical oxidative stress in CSF is of prognostic utility.

Efficacy of ozonized water for the treatment of erosive oral lichen planus: a randomized controlled study.

BACKGROUND: Management of erosive Oral Lichen Planus (eOLP) is challenging. Currently, topical corticosteroids are widely used as first-line therapy, but they might be associated with side-effects and incomplete clinical response. Among non-pharmacological strategies, ozone at low medical concentration has proven to induce a mild activation of protective anti-oxidant pathways, thus exerting therapeutic effects in many inflammatory diseases. The aim of this randomized controlled study was to investigate the effectiveness of ozonized water in association with conventional topical corticosteroids for the treatment of eOLP. MATERIAL AND METHODS: Fifty-one patients were included in the study and randomized into 2 groups: study group (n=26) included patients receiving ozonized water treatment; control group (n=25) included patients receiving placebo treatment (i.e. double-distilled water). Treatment protocol consisted of 1-minute oral rinses, repeated for 4 times, twice a week for 4 weeks. All patients received conventional corticosteroid topical therapy (betamethasone soluble tablets, 2 rinses/day for 4 weeks). Assessment of size of lesions, sign and pain scores was performed before treatment, after 2 weeks of treatment (T1) and at the end of 4-week treatment (T2). Efficacy Index (EI) of treatment, candidiasis and relapse rates were also recorded. RESULTS: All patients experienced significant improvement of sign and pain scores with a higher rate of improvement in ozone-treated group (T1 improvement rates: Thongprasom 92.2% vs 28%; VAS pain 76.9% vs 32%; p<0.05). Pain and size reduction were significantly higher in ozone-treated group both at T1 and T2 (p<0.05). Ozone-treated group showed a higher EI at every time point (T0-T2: 72.77% vs 37.66%, p<0.01). Candidiasis (32% vs 11.5%) and relapse (40% vs 34.6%) rates were higher in control group, however the differences were not statistically significant. CONCLUSIONS: Within the limitations of this study, ozonized water seems to be effective as an adjunct therapy, in combination with topical corticosteroids, for the treatment of eOLP.

Photobiomodulation therapy for the management of recurrent aphthous stomatitis in children: clinical effectiveness and parental satisfaction.

BACKGROUND: This study aims to evaluate the effectiveness of the photobiomodulation therapy (PBMT) in the treatment of minor recurrent aphthous stomatitis (MiRAS) in children, in terms of pain relief, lesion size reduction and the parental satisfaction of the therapy. MATERIAL AND METHODS: This randomized controlled study was carried out on 60 children with clinical diagnosis of MiRAS. Patients were randomized into two groups: group A receiving laser therapy and group B receiving sham therapy (placebo). Laser therapy (diode laser, λ: 645 nm) was administered on day 1 (T0) for three consecutive days. Patients were evaluated also on day 4 (T1), on day 7 (T2) and on day 10 (T3). Oral aphthous lesions size was assessed through a periodontal probe to measure the diameter length (mm); pain was evaluated through the Visual Analogue Scale (VAS); parental satisfaction was assessed through a questionnaire. RESULTS: The difference in the reduction of ulcers diameters between the two groups resulted statistically significant at T1 and at T2 (p<0.05). A statistically significant difference in pain reduction between two groups was found at T1 (p<0.05). No statistically significant difference between the two groups of parents was found as concerns the parental acceptance of the procedure and the discomfort for the need of multiple appointments. CONCLUSIONS: PBMT is to be considered effective in the treatment of MiRAS in children and well- accepted by the parents of the children themselves.

Juvenile idiopathic arthritis-associated uveitis: a retrospective analysis from a centre of South Italy.

PURPOSE: To investigate the clinical and laboratory characteristics of the children affected by juvenile idiopathic arthritis (JIA) who developed uveitis. METHODS: In this retrospective study, we have examined data of 109 patients aged from 3 to 16 years, affected by JIA and followed at Paediatrics Rheumatology Clinic and Ophthalmology Clinic of University Hospital of Messina in the period from 2007 to 2017. The main outcome measures were clinical and laboratory findings related to JIA and ocular involvement. The prevalence of ocular signs and symptoms was determined and correlated with age. RESULTS: Twenty-one (19.3%) subjects developed uveitis. Two different peaks of age with ocular involvement were registered. The first occurred between 4 and 6 years and the second between 10 and 12 years. All subjects in the first group resulted to be female, presented oligoarticular arthritis and chronic anterior uveitis. In the second group, the 84% of patients were male with different types of JIA and acute anterior uveitis. The prevalence of ocular complications was higher in the first group. CONCLUSIONS: Two peaks of age emerged and were characterized by different clinical outcomes of arthritis and ocular involvement. The first occurred between 4 and 6 years and interested females affected by oligoarticular JIA who develop chronic anterior uveitis. The second appeared at 10-12 years and interested older males affected by different types of JIA with acute anterior uveitis. Early diagnosis and cooperation between paediatric rheumatologist and ophthalmologist are of great importance in the proper management of JIA children with uveitis.

Nephrotic syndrome: immunological mechanisms.

Nephrotic Syndrome (NS) is a rare diseases (around 2-7 cases per 100.000 children per year) characterized by proteinuria ≥50 mg/kg/day (or ≥40 mg/m2/h) or a proteinuria/creatininuria ratio >2 (mg/mg); hypoalbuminaemia less than 25 g/l and edema. The protein leakage, with the consequent hypoalbunaemia and edema, due to podocyte alterations may be caused by genetic diseases, immunological mechanisms, infections, toxins or malignancy. However, most commonly the exact etiology is unknow. The idiopathic NS may be classified based on response to corticosteroid therapy or the hytological appearance. The first classification identifies steroid-resistant NS (no response after 4 weeks of steroid therapy); frequently relapsing NS (≥ 2 relapses in first 6 months or ≥4 relapses in 1-year); steroid dependent NS (relapses during steroid decalage or within 2 weeks from steroid therapy interruption). The hystological classification is based on light and electron microscopy after renal biopsy, which is indicated in case of onset disease before 1 year or after 12 years of age. Macroscopic hematuria: persistent hypertension and/or microscopic hematuria and/or low plasma C3 renal failure not related to hypovolemia; steroid resistence: secondary or relatedsyndromes NS. Minimal change disease (MCD) is the most common form of idiopahtic NS in children, with good response to steroid treatment, and it is characterized by normal glomerular appearance on light microscopy and evidence of podocyte foot alterations on electron microscopy, due to immunological related damage. Focal segmental glomerulosclerosis (FSGS) is described inidiopahtic NS, particularly in steroiddependent or steroid-resistant forms, and is characterized by evidence of focal glomerular damage with secondary sclerosis and adhesion with Bowman's capsule; the electron appearance is the same of MCD one. Recent authors hypotizethat the FSGS is an evolution of MCD. These 2 idiopathic NS forms may be expression of the same immunological disease, with 2 different severity grades; so they may be considered different moments of the same disease spectrum. Less common idiopathic NS forms are membrano proliferative glomerulonephritis; membranous nephropathy; IgM-nephropathy; C1q nephropathy and thin basement membrane disease (1, 2, 3).

Renal anomalies in newborns with vacterel association: case series and literature review.

Nocturnal enuresis (NE) was defined by the World Health Organization (ICD-10) and the American Psychiatric Association (DSM-5) as bed-wetting in children aged >5 years. In cases of mental retardation, the developmental age may be equivalent to 5 years. In this review, we focus on the current knowledge about the etiology of enuresis and the most recent therapeutical options. Both non-pharmacological and pharmacological therapies are included, although the relative effectiveness of each remains uncertain. To date, motivational, alarm and drug therapies are the mainstay of treatment. Alarm therapy remains the first-line treatment modality for NE, while desmopressin is the most commonly used medical treatment.

Efficacy of the photobiomodulation therapy in the treatment of the burning mouth syndrome.

BACKGROUND: This study aims to evaluate the efficacy of the photobiomodulation therapy (PBMT) - in terms of pain and of quality of life- in patients affected by burning mouth syndrome (BMS). MATERIAL AND METHODS: This study was designed as a randomised double-blinded prospective study. Patients diagnosed with BMS in the period from June 2015 to June 2018 were recruited. The patients were randomised into two groups and each received treatment once a week for ten weeks: group A received laser therapy (K Laser Cube 3) while group B was given sham therapy (placebo). Pain was evaluated through the Visual Analogue Scale (VAS) and quality of life was assessed with the short form of the Oral Health Impact Profile (OHIP-14). Assessment was done at baseline and after every therapy session. The researchers were blind to the randomised allocations. RESULTS: A total of 85 patients were analysed. Group A (laser treatment) was composed of 43 patients while group B (sham therapy) of 42 patients. Patients treated with PBMT showed a significant decrease in symptoms ( p=0.0008) and improved quality of life related to oral health ( p=0.0002). CONCLUSIONS: PBMT has demonstrated to have a positive effect in relieving BMS symptoms and in improving a patient's overall quality of life.

Effectiveness of a spray containing 1% malic acid in patients with xerostomia induced by graft-versus-host disease.

BACKGROUND: To evaluate the clinical effectiveness of a topical sialogogue spray (malic acid, 1%) in the treatment of xerostomia in patients with chronic Graft versus Host Disease (cGVHD). MATERIAL AND METHODS: This study was designed as a randomized double-blind clinical study. Twenty-eight patients with cGVHD suffering from xerostomia were divided into 2 groups: the first group (14 patients) received a topical sialagogue spray containing malic acid 1% (SalivAktive®) whereas the second group (14 patients) received a placebo. Both groups received treatment for 2 weeks. Dry Mouth Questionnaire (DMQ) scores and unstimulated salivary flows rate were collected before and after treatment. RESULTS: DMQ scores increased significantly from 1.3 ± 0.4 to 3.5 ± 0.4 points (p<0.05) after two weeks of treatment with malic acid, whereas in the control group DMQ scores increased from 1.2 ± 0.7 points to 1.4 ± 0.6 (p>0.05). The unstimulated salivary flow rate in patients treated with malic acid increased significantly from 0.15 ± 0.06 mL/min to 0.24± 0.08 mL/min, while that of the patients treated with placebo went from 0.16 ± 0.07 mL/min to 0.17 ± 0.09 mL/min (p>0.05). CONCLUSIONS: Malic acid 1% spray can be considered effective in the treatment of GVHD induced xerostomia.

Adipocytes sustain pancreatic cancer progression through a non-canonical WNT paracrine network inducing ROR2 nuclear shuttling.

BACKGROUND: Solid epidemiological evidences connect obesity with incidence, stage and survival in pancreatic cancer. However, the underlying mechanistic basis linking adipocytes to pancreatic cancer progression remain largely elusive. We hypothesized that factors secreted by adipocytes could be responsible for epithelial-to-mesenchymal transition (EMT) induction and, in turn, a more aggressive phenotype in models of pancreatic preneoplastic lesions. METHODS: We studied the role of factors secreted by two adipogenic model systems from primary human bone marrow stromal cells (hBMSCs) in an in vitro experimental cell transformation model system of human pancreatic ductal epithelial (HPDE) cell stably expressing activated KRAS (HPDE/KRAS),Results:We measured a significant induction of EMT and aggressiveness in HPDE and HPDE/KRAS cell lines when cultured with medium conditioned by fully differentiated adipocytes (ADIPOCM) if compared with the same cells cultured with medium conditioned by hBMSC (hBMSCCM) from two different healthy donors. Several genes coding for soluble modulators of the non-canonical WNT signaling pathway, including FRZB, SFRP2, RSPO1, WNT5A and 5B were significantly overexpressed in fully differentiated adipocytes than in their respective in hBMSC. ADIPOCM induced the overexpression and the nuclear translocation of the Frizzled family member receptor tyrosine kinase-like orphan receptor (Ror) 2 in HPDE and HPDE/KRAS cells. Vantictumab, an anti-Frizzled monoclonal antibody, reduced ROR2 nuclear translocation and in turn the EMT and aggressiveness in HPDE and HPDE/KRAS cells. CONCLUSIONS: We demonstrated that adipocytes could induce EMT and aggressiveness in models of pancreatic preneoplastic lesions by orchestrating a complex paracrine signaling of soluble modulators of the non-canonical WNT signaling pathway that determine, in turn, the activation and nuclear translocation of ROR2. This signaling pathway could represent a novel target for pancreatic cancer chemoprevention. Most importantly, these factors could serve as novel biomarkers to select a risk population among obese subjects for screening and, thus, early diagnosis of pancreatic cancer.

Histological evaluation of periodontal ligament in human after orthodontic treatment with piezosurgery and monolateral tooth dislocation and ligament distraction technique: a first morphologic and histologic evaluation.

Traditional orthodontic tooth movement is based on the concept that application of a protracted force causes alveolar bone remodelling and adaptive changes in periodontal and dental tissues. Thus, if orthodontic tooth movement is described as a biological bone reaction to orthodontic forces mediated by the periodontal ligament (PDL), this event involves a series of sophisticated signal transduction processes that allows the PDL compression with specific histologic and biomolecular modifications. However, the preservation of the integrity of the PDL is generally difficult to achieve when it is associated with a long duration of orthodontic treatment. A total of 20 Caucasian patients with different dental-skeletal were treated using the Monocortical Tooth Dislocation and Ligament Distraction (MTDLD) technique with Piezosurgery associated with morphologic and histological evaluation of the PDL. The histological results obtained, confirm a good clinical outcome with an improvement of the speed on orthodontic treatment without any signs of tissue injury of PDL fiber without areas of hyalinization. The data suggests that MTDLD with Piezosurgery seems to be a valid alternative to the traditional orthodontic movement in adult patients preserving the anatomy and the integrity of PDL.

CPAP by helmet for treatment of acute respiratory failure after pediatric liver transplantation.

ARF after pediatric liver transplantation accounts for high rate of morbidity and mortality associated with this procedure. The role of CPAP in postoperative period is still unknown. The aim of the study was to describe current practice and risk factors associated with the application of helmet CPAP. In this retrospective observational cohort study, 119 recipients were divided into two groups based on indication to CPAP after extubation. Perioperative variables were studied, and determinants of CPAP application were analyzed in a multivariate logistic model. Sixty patients (60/114) developed ARF and were included in the CPAP group. No differences were found between the two groups for primary disease, graft type, and blood product transfused. At multivariate analysis, weight <11 kg (OR = 2.9; 95% CI = 1.1-7.3; P = .026), PaO2 /FiO2 <380 before extubation (OR = 5.4; 95% CI = 2.1-13.6; P < .001), need of vasopressors (OR = 2.6; 95% CI = 1.1-6.4; P = .038), and positive fluid balance >148 mL/kg (OR = 4.0; 95% CI = 1.6-10.1; P = .004) were the main determinants of CPAP application. In the CPAP group, five patients (8.4%) needed reintubation. Pediatric liver recipients with lower weight, higher need of inotropes/vasopressors, higher positive fluid balance after surgery, and lower PaO2 /FiO2 before extubation were at higher odds of developing ARF needing CPAP application.

Dexmedetomidine is effective and safe during NIV in infants and young children with acute respiratory failure.

BACKGROUND: Noninvasive ventilation (NIV) is increasingly utilized in infants and young children, though associated with high failure rates due to agitation and poor compliance, mostly if patient-ventilator synchronization is required. METHODS: A retrospective cohort study was carried out in an academic pediatric intensive care unit (PICU). Dexmedetomidine (DEX) was infused as unique sedative in 40 consecutive pediatric patients (median age 16 months) previously showing intolerance and agitation during NIV application. RESULTS: During NIV clinical application both COMFORT-B Score and Richmond Agitation-Sedation Scale (RASS) were serially evaluated. Four patients experiencing NIV failure, all due to pulmonary condition worsening, required intubation and invasive ventilation. 36 patients were successfully weaned from NIV under DEX sedation and discharged from PICU. All patients survived until home discharge. CONCLUSION: Our data suggest that DEX may represent an effective sedative agent in infants and children showing agitation during NIV. Early use of DEX in infants/children receiving NIV for acute respiratory failure (ARF) should be considered safe and capable of improving NIV, thus permitting both lung recruitment and patient-ventilator synchronization.

Modulation of host plant immunity by Tobamovirus proteins.

BACKGROUND: To establish successful infection, plant viruses produce profound alterations of host physiology, disturbing unrelated endogenous processes and contributing to the development of disease. In tobamoviruses, emerging evidence suggests that viral-encoded proteins display a great variety of functions beyond the canonical roles required for virus structure and replication. Among these, their modulation of host immunity appears to be relevant in infection progression. SCOPE: In this review, some recently described effects on host plant physiology of Tobacco mosaic virus (TMV)-encoded proteins, namely replicase, movement protein (MP) and coat protein (CP), are summarized. The discussion is focused on the effects of each viral component on the modulation of host defense responses, through mechanisms involving hormonal imbalance, innate immunity modulation and antiviral RNA silencing. These effects are described taking into consideration the differential spatial distribution and temporality of viral proteins during the dynamic process of replication and spread of the virus. CONCLUSION: In discussion of these mechanisms, it is shown that both individual and combined effects of viral-encoded proteins contribute to the development of the pathogenesis process, with the host plant's ability to control infection to some extent potentially advantageous to the invading virus.