Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS. METHODS: Seventy-one adult males (median age 41 years, range 18-64) with 47, XXY KS were consecutively enrolled by two Endocrinology and Andrology Units (IRCCS Humanitas Research Hospital in Milan and ASST Spedali Civili in Brescia). Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density (BMD) at lumbar spine, femoral neck and total hip, TBS and body composition. Prevalence of VFs was assessed by quantitative morphometry on lateral spine X-rays. RESULTS: VFs were detected in 14 patients (19.7%), without significant association with low BMD (p = 0.912). In univariate logistic regression analysis, VFs were significantly associated with truncal/leg fat ratio (OR 2.32 per tertile; 95% CI 1.05-5.15; p = 0.038), whereas impaired TBS (detected in 23.4% of subjects) was associated with older age at study entry (p = 0.001) and at diagnosis of disease (p = 0.015), body mass index (BMI; p = 0.001), waist circumference (p = 0.007), fat mass index (FMI; p < 0.001), FMI/lean mass index (LMI) ratio (p = 0.001). Prevalence of VFs was not significantly different between subjects with impaired TBS as compared to those with normal TBS (26.7 vs. 18.4%; p = 0.485). Skeletal end-points were not significantly associated with duration of testosterone replacement therapy and serum testosterone and 25hydroxyvitamin D values. CONCLUSION: Body composition might influence bone quality and risk of VFs in subjects with KS.

Chronic inflammatory demyelinating polyradiculoneuropathy: can a diagnosis be made in patients not fulfilling electrodiagnostic criteria?

BACKGROUND AND PURPOSE: The aim was to identify the clinical and diagnostic investigations that may help to support a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in patients not fulfilling the European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria. METHODS: The data from patients with a clinical diagnosis of CIDP included in a national database were retrospectively reviewed. RESULTS: In all, 535 patients with a diagnosis of CIDP were included. This diagnosis fulfilled the EFNS/PNS criteria in 468 patients (87.2%) (definite in 430, probable in 33, possible in three, while two had chronic immune sensory polyradiculopathy). Sixty-seven patients had a medical history and clinical signs compatible with CIDP but electrodiagnostic studies did not fulfill the EFNS/PNS criteria for CIDP. These patients had similar clinical features and frequency of abnormal supportive criteria for the diagnosis of CIDP compared to patients fulfilling EFNS/PNS criteria. Two or more abnormal supportive criteria were present in 40 (61.2%) patients rising to 54 (80.6%) if a history of a relapsing course as a possible supportive criterion was also included. Increased cerebrospinal fluid proteins and response to immune therapy most frequently helped in supporting the diagnosis of CIDP. Response to therapy was similarly frequent in patients fulfilling or not EFNS/PNS criteria (87.3% vs. 85.9%). CONCLUSIONS: Patients with a clinical diagnosis of CIDP had similar clinical findings, frequency of abnormal supportive criteria and response to therapy compared to patients fulfilling EFNS/PNS criteria. The presence of abnormal supportive criteria may help in supporting the diagnosis of CIDP in patients with a medical history and clinical signs compatible with this diagnosis but non-diagnostic nerve conduction studies.

Risk factors for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): antecedent events, lifestyle and dietary habits. Data from the Italian CIDP Database.

BACKGROUND AND PURPOSE: The role of lifestyle and dietary habits and antecedent events has not been clearly identified in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: Information was collected about modifiable environmental factors and antecedent infections and vaccinations in patients with CIDP included in an Italian CIDP Database. Only patients who reported not having changed their diet or the lifestyle habits investigated in the study after the appearance of CIDP were included. The partners of patients with CIDP were chosen as controls. Gender-matched analysis was performed with randomly selected controls with a 1:1 ratio of patients and controls. RESULTS: Dietary and lifestyle data of 323 patients and 266 controls were available. A total of 195 cases and 195 sex-matched controls were used in the analysis. Patients eating rice at least three times per week or eating fish at least once per week appeared to be at decreased risk of acquiring CIDP. Data on antecedent events were collected in 411 patients. Antecedent events within 1-42 days before CIDP onset were reported by 15.5% of the patients, including infections in 12% and vaccinations in 1.5%. Patients with CIDP and antecedent infections more often had an acute onset of CIDP and cranial nerve involvement than those without these antecedent events. CONCLUSIONS: The results of this preliminary study seem to indicate that some dietary habits may influence the risk of CIDP and that antecedent infections may have an impact on the onset and clinical presentation of the disease.

Longitudinal neurophysiological assessment of intramuscular type-A botulin toxin in healthy humans.

The aim of this study is to assess the neurophysiological abnormalities of type A botulin toxin-infiltrated human muscle, and their evolution over time. Seried cMAP measurements, 3 and 20 Hz repetitive nerve stimulation, EMG, SFEMG over 3 months from toxin injection. Our findings consist in lack of decrement with 3 Hz repetitive nerve stimulation and facilitation with 20 Hz repetitive nerve stimulation; progressive increasing of jitter; early appearance of fibrillations; small and short motor unit action potential in the first 3 weeks, followed by increasing of MUAP amplitude and duration, with polyphasic morphology. Although claimed as highly specific and sensible, neuromuscular junction facilitation is an inconstant finding in human botulism. Therefore, lack of neuromuscular junction facilitation cannot exclude a diagnosis of botulism. Our findings are compatible with a process of acute denervation followed by distal reinnervation, favored by terminal nerve sprouting.

Probiotic mixture supplementation in the preventive management of trinitrobenzenesulfonic acid-induced inflammation in a murine model.

Inflammatory bowel diseases (IBD) are characterized by inflammatory conditions of the intestine. Probiotic bacteria (PB) can have beneficial effects in several gastrointestinal disorders. The objectives of this study were: (i) to provide an acute experimental IBD model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in CD-1 mice, and (ii) to assess the preventive effects of Citogenex (Lactobacillus casei and Bifidobacterum lactis) supplementation on intestinal tissues and microbiota. Mice were inoculated intrarectally with saline, ethanol or different TNBS solutions. 1%TNBS induced clinical signs of colitis (P less than 0.01) and histological damage (P less than 0.01). Based on these results, mice were pre-treated with Citogenex or saline for 1, 2 or 3 weeks before 1%TNBS treatment. Probiotic pre-treatment determined a reduction of clinical signs (P less than 0.05), histological alterations of colitis (P less than 0.05) and increased beneficial bacteria (P less than 0.05). This study confirms that TNBS-induced colitis in CD-1 mice is useful for studying the mechanisms involved in IBD pathogenesis, and pre-treatment with Citogenex prevents the intestinal damage induced by TNBS.

Western blot expression of 5-lipoxygenase in the brain from striped dolphins (stenella coeruleoalba) and bottlenose dolphins (tursiops truncatus) with or without encephalitis/meningo-encephalitis of infectious nature.

Dolphin Morbillivirus (DMV), Toxoplasma gondii and Brucella ceti are pathogens of major concern for wild cetaceans. Although a more or less severe encephalitis/meningo-encephalitis may occur in striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) infected by the aforementioned agents, almost no information is available on the neuropathogenesis of brain lesions, including the neuronal and non-neuronal cells targeted during infection, along with the mechanisms underlying neurodegeneration. We analyzed 5-lipoxygenase (5-LOX) expression in the brain of 11 striped dolphins and 5 bottlenose dolphins, affected or not by encephalitic lesions of various degrees associated with DMV, T. gondii and B. ceti. All the 8 striped dolphins with encephalitis showed a more consistent 5-LOX expression than that observed in the 3 striped dolphins showing no morphologic evidence of brain lesions, with the most prominent band intensity being detected in a B. ceti-infected animal. Similar results were not obtained in T. gondii-infected vs T. gondii-uninfected bottlenose dolphins. Overall, the higher 5-LOX expression found in the brain of the 8 striped dolphins with infectious neuroinflammation is of interest, given that 5-LOX is a putative marker for neurodegeneration in human patients and in experimental animal models. Therefore, further investigation on this challenging issue is also needed in stranded cetaceans affected by central neuropathies.

Gene Expression and Localization of NGF and Its Cognate Receptors NTRK1 and NGFR in the Sex Organs of Male Rabbits.

Experiments were devised to characterize the expression of nerve growth factor, beta polypeptide (NGF), and its cognate receptors neurotrophic tyrosine kinase receptor type 1 (NTRK1) and nerve growth factor receptor (NGFR) in rabbit male sex organs, as well as the concentrations of NGF in both seminal and blood plasma of sexually mature male rabbits. Immunoreactivity and gene expression for NGF and cognate receptors were detected in testis, prostate gland and seminal vesicle. The highest levels of NGF and NTRK1 transcripts were found in the prostate, while intermediate expressions were found in the testis. NGFR transcripts were expressed at the same levels in both testis and prostate and were more abundant than in seminal vesicles. The widespread distribution of NGF in all prostate glandular cells, together with its relative high mRNA abundance, confirms that the prostate of rabbits is the main source of this neurotrophin. In conclusion, the present data suggest that the NGF system is involved in the testicular development and spermatogenesis of rabbits and that NGF may act as a potential ovulation-inducing factor being abundantly present in the seminal plasma.

The growth of Streptococcus mutans in different milks for infant feeding.

After birth various bacterial species, mainly streptococci, colonize the oral cavity and are frequently isolated from carious lesions in children. Previous studies suggest that an earlier colonization of a child's mouth by cariogenic organisms might be related to a higher risk of caries. The aim of this study is to assess the influence of different milks for infant feeding on the growth of Streptococcus mutans (SM) colonies. Three human milk samples from three different mothers and five infant formulas were tested. To prepare the bacterial inoculum, SM was grown in Brain Heart Infusion broth for 18 hours at 37°C in microaerophilic atmosphere. The growth of SM was determined immediately after the inoculation of milks (T0) and after 24 hours (T24) of incubation. After 24 hours of incubation (ΔT= CFUs/ml at T24 – CFUs/ml at T0) the bacterial growth changes were different among milks. Among the complementary milks tested, ΔT of formulas supplemented with Lactobacillus reuteri and with Bifidobacterium lactis was lower than those of non-supplemented formula. In conclusion, on the basis of the reduced SM growth in milks supplemented with probiotics, we may speculate that these formulas have a preventive effect on the development of caries in children.

Risk factors affecting quality of life in a group of Italian children with asthma.

The measure of Quality of Life (QoL) has become one of the most important criteria used to assess the impact of chronic illness, such as asthma, on the patient’s daily life, in adults and children alike. The objective of our open observational study was to measure the QoL and analyze several factors that potentially affect QoL, such as symptoms and functional respiratory parameters, in a cohort of children with asthma. One hundred and twenty-seven children with asthma, 6 to 14 years of age, living in the city of Rome, were enrolled as outpatients. They were subjected to Skin Prick Tests (SPT), underwent spirometry and filled out the Pediatric Asthma Quality of Life Questionnaire (PAQLQ). One hundred and eleven children were diagnosed with intermittent asthma, 12 (10%) with mild asthma, and four with moderate persistent asthma. Ninety-six children had a positive SPT. The mean total score of QoL, obtained from the questionnaire, was 5.4 (∓1.2 SD). Two QoL groups were created. Children with total QoL score <5.5 were included in the “Lower QoL” score group while children with total QoL score ≥ 5.5 were included in the “Higher QoL” score group. Children in the Higher group and their mothers had a higher mean age, suffered from fewer asthma exacerbations during the year preceding the study, and showed a higher mean value of forced expiratory volume (FEV1) compared to the children in the Lower category. Using Logistic regression we identified the main factors that may affect QoL as FEV1, symptoms in the previous year and mother’s age. QoL is correlated with the frequency of asthma exacerbations and FEV1 values. Furthermore, our research shows that a significant impairment of QoL may also occur in patients with normal lung function, pointing out the importance of evaluating QoL in all children with asthma.

One drop only. Easy and rapid Raman evaluation of ß-carotene in olive oil and its relevance as an index of olive fly attack.

This paper presents, for the first time, a method for the rapid quantification of ß-carotene in olive oil by Raman spectroscopy. Using a 532 nm Raman laser source, our procedure requires only one drop (100 µL) of oil, for ß-carotene content to be determined. Results show that ß-carotene content is associated with the lutein/ß-carotene ratio, a parameter whose value describes how healthy the olives were before processing, specifically whether an olive fly attack occurred. Since olive fly attacks are not always visible to the oil producers, this method gives them the means to control the validity of the prevention strategies they adopted.

Transient hypogammaglobulinemia of infancy: intravenous immunoglobulin as first line therapy.

IVIG (Intravenous immunoglobulin) have significantly improved the prognosis and the quality of life of immunodeficient patients and are routinely used as substitutive therapy. Transient hypogammaglobulinemia of infancy (THI) is a primary humoral immunodeficiency characterized by a transient IgG defect, but is not considered as a disease that justifies substitutive treatment and thus the use of IVIG as an alternative to antibiotic prophylaxis remains controversial also in symptomatic children. We treated 13 THI children severely symptomatic with IVIG (400mg/kg/every 3 weeks ) for a limited period (2 or 3 months) and followed them for 1 to 3 years. During the follow-up, the frequency of overall infections decreased approximately tenfold (from 0.39 to 0.047 infection/month per child) and no severe infections were reported. Although this study lacks untreated controls, the results suggest that the observed clinical improvement is correlated to IVIG therapy. Furthermore, our study suggests that the infused IVIG have no long-term effect on endogenous IgG production and do not lengthen the immunodeficiency condition since all children produced a normal amount of specific IgG in response to vaccination carried out 5 months after the end of infusions. In conclusion, our results suggest that IVIG may stop the vicious circle of infection-immunodeficiency and should be considered as a first line therapy in highly symptomatic THI children.

Risk factors for upper airway diseases.

Upper respiratory infection is the most common reason for seeking medical care for children. Recurrent viral respiratory infections and subsequent complications are a burden for children, their families and society. It has been estimated that at least 6 percent of children younger than 6 yr of age presents recurrent respiratory infections, as consequence of an increased exposure to infectious agents during the first years of life, when immune functions are still immature. Pediatricians must identify risk factors predisposing to upper respiratory tract infections and plan specific preventive strategies, ie avoidance of precocious day-care attendance and secondary smoke. Vaccination against influenza and pneumococcal diseases should always be recommended.

Chronotypes in menstrual migraine: a case-control study.

Migraine attacks have a seasonal, menstrual and circadian periodicity, suggesting a role of chronobiological mechanisms probably related to a hypothalamic involvement. The aim of the study was to evaluate the chronotypes in patients with menstrual migraine, a migraine sub-type with a cyclical recurrence compared to normal female. Ninety-three patients with ICHD-II diagnosis of pure menstrual migraine and menstrually-related migraine were recruited and compared to 85 age-matched healthy women. The Italian version of Morningness-Eveningness Questionnaire was administered to identify circadian preference of our participants. No differences were found regarding the distribution of chronotypes in patients with menstrual migraine and healthy controls. The study did not confirm the presence of a morning and evening preference among migraineurs as previously reported.

Prospective analysis between the therapy of immunosuppressive medication and allogeneic microchimerism after liver transplantation.

After liver transplantation, migration of donor-derived hematopoietic cells to recipient can be detected in peripheral blood. This state is termed microchimerism. The aim of this study was to investigate prospectively the presence of allogeneic microchimerism, the occurrence of acute cellular rejection and the level of immunosuppression in transplanted patients. Microchimerism occurrence between 10 days and 12 months after liver transplantation was analyzed in 47 patients aged between 15 and 65 by a two-stage nested PCR/SSP technique to detect donor MHC HLA-DR gene specifically. A pre-transplant blood sample was collected from each patient to serve as individual negative control. Microchimerism was demonstrated in 32 (68%) of the 47 patients; of these, only 10 patients (31.2%) presented rejection. Early microchimerism was observed in 25 patients (78.12%) and late microchimerism in 7 patients (21.8%). Among the patients with microchimerism, 14 were given CyA and 18 were given FK506. In the group without microchimerism, 12 patients were given CyA and 03 were given FK506. There was a significant association between the presence of microchimerism and the absence of rejection (p=0.02) and also between microchimerism and the type of immunosuppression used. Our data indicate that microchimerism and probably differentiation of donor-derived leukocytes can have relevant immunologic effects both in terms of sensitization of recipient and in terms of immunomodulation toward tolerance induction.

Vernal Keratoconjunctivitis: an update focused on clinical grading system.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a severe disease with a prevalence of < 1 case out of 10,000 in Europe, which occurs mainly in pediatric age and is characterized by a severe and often bilateral chronic inflammation of the ocular surface. The diagnosis is generally confirmed by the finding at the ocular examination of conjunctival hyperemia, papillary hypertrophy in the tarsal conjunctiva, giant papillae, papillae in the limbus region. OBJECTIVE: Aim of this review is to provide an updated overview on the disease focused on clinical grading system, searching papers published in the last decade on VKC in scientific databases. RESULTS: Currently there are no standardized criteria for diagnosis of VKC and there is no uniformity to define disease severity, which makes difficult to diagnose and treat the disease. CONCLUSIONS: Given the wide overlap of the symptoms of VKC with the allergic conjunctivitis, criteria of probable, possible or improbable diagnosis are needed, providing pediatricians with parameters useful for deciding whether to drive the patient to the ophthalmologist for diagnostic confirmation.

Extragastrointestinal stromal tumor and liver transplantation: case report and review.

The occurrence of de novo malignant neoplasias has been shown in postransplant patients under imunosuppression. It is the second leading cause of late death in liver transplant recipients. The greatest incidence is seen in cancers associated with chronic infection by human papilloma virus, skin cancers, oropharyngeal, and gastrointestinal (GI) malignancies. GI stromal tumors (GISTs) are the most common mesenchymal tumors of the GI tract. Rare cases are identified outside the GI tract are collectively known as extragastrointestinal stromal tumors (EGISTs). We present an EGIST case in a liver transplantation patient. A 64-year-old man underwent liver transplantation because of cirrhosis (hepatitis B virus and alcoholism) and hepatocellular carcinoma. Histopathologic findings revealed 2 trabecular hepatocellular carcinomas: a 3.5-cm-diameter lesion located at segment VIII and another 2-cm one at segment V. Seven months later, he noticed a hardened, mobile, painless, 3-cm subcutaneous nodule in the perineum localized in the right lateral quadrant 2 cm distant from the anus. A surgical resection with 1 cm margin yielded a histopathology report of a 5.0 x 3.0 cm spindle cell stromal tumor. The immunohistochemical profile was compatible with a GIST, with 5 mitosis per 50 high-powered fields. This tumor is extremely rare after liver transplantation but has shown a good outcome up to now.