Sleep quality burden in chronic rhinosinusitis with nasal polyps and its modulation by dupilumab.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with a substantial burden on patients' quality of life and impaired sleep quality. The most common CRSwNP endotype is characterized by type 2 inflammation, with enhanced production of interleukin (IL)-4, IL-5, and IL-13. Dupilumab is a monoclonal antibody against IL-4 receptor-α, which inhibits both IL-4 and IL-13 signaling, and was recently approved for treatment of CRSwNP. OBJECTIVE: We investigated the effect of dupilumab on the sleep quality of patients with CRSwNP in a real-life setting. METHODS: Patients were evaluated at baseline and after 1 and 3 months of dupilumab treatment by means of the Epworth sleepiness scale (ESS), insomnia severity index (ISI), Pittsburgh sleep quality index (PSQI), and sinonasal outcome test 22 (SNOT-22) sleep domain. RESULTS: A total of 29 consecutive patients were enrolled, and their baseline sleep quality assessment were as follows: ESS of 7.9 (± 4.5); ISI of 13.1 (± 6.2); PSQI of 9.2 (± 3.7); and SNOT-22 sleep domain of 12.1 (± 4.2). Excessive daily sleepiness, insomnia, and globally impaired sleep quality were present in 24.1%, 79.3%, and 93.1% respectively. Treatment with dupilumab was associated with significant improvement in ESS, ISI, PSQI, and SNOT-22 sleep domain with concomitant reduction of the proportion of patients with insomnia and globally impaired sleep quality. CONCLUSION: CRSwNP was associated with a significant impact on global sleep quality, in particular, insomnia, and treatment with dupilumab induced a rapid improvement (after 1 single month of treatment) in all the sleep quality parameters, suggesting that sleep disturbances should be more carefully evaluated as an additional outcome in these patients.

Robotic-Assisted Rehabilitation for Post-Stroke Shoulder Pain: A Systematic Review.

Post-stroke shoulder pain (PSSP) is a debilitating consequence of hemiplegia, often hindering rehabilitation efforts and further limiting motor recovery. With the advent of robotic-assisted therapies in neurorehabilitation, there is potential for innovative interventions for PSSP. This study systematically reviewed the current literature to determine the effectiveness of robotic-assisted rehabilitation in addressing PSSP in stroke patients. A comprehensive search of databases was conducted, targeting articles published up to August 2023. Studies were included if they investigated the impact of robotic-assisted rehabilitation on PSSP. The outcome of interest was pain reduction. The risk of bias was assessed using the Cochrane database. Of the 187 initially identified articles, 3 studies met the inclusion criteria, encompassing 174 patients. The reviewed studies indicated a potential benefit of robotic-assisted rehabilitation in reducing PSSP, with some studies also noting improvements in the range of motion and overall motor function. However, the results varied across studies, with some showing more significant benefits than others, because these use different protocols and robotic equipment.

Effect of feed restriction and refeeding on body condition, digestive functionality and intestinal microbiota in rainbow trout (Oncorhynchus mykiss).

The aim of the present work was to investigate the influence of fasting and refeeding on body condition, gut physiology and microbiota in reared O. mykiss. Ninety-six fish were randomly allotted among three groups subjected to different feeding plan: C (control, fed for 5 weeks); R (restricted ration over 3 weeks followed by 2 weeks feeding); F (fasted over 3 weeks followed by 2 weeks feeding) in a well's fresh water flow-through rearing plan. Sampling occurred at 0, 1, 2, 4, 7, 14 days during the refeeding period. At day 0 and throughout the feeding period until day 14, the weight of the fish was significantly affected by the feeding restriction. Feed deprivation reduced significantly the viscerosomatic and hepatosomatic indexes. Brush border membrane enzymes' specific activity was modulated by feeding regimes until day 7, to level in all experimental groups at day 14. At the end of the restricted/fasted period, the microbiota of the C group was made up of 70% of Actinobacteria, 24% of Proteobacteria, 4.2% of Firmicutes and < 1% of Bacteroides, while the restricted and fasted group were characterized by a strong reduction of Actinobacteria, and a significant increase in Bacteroidetes and Firmicutes. The feed deprivation determined a dysbiosis, allowing the development of different commensal or pathogenic bacteria. In conclusion, the effects of 2 weeks of feed deprivation, excluding those related to body weight, are gradually mitigated by refeeding, which allows the restoration of digestive functions and a healthy intestinal microbiota.

ddRAD-seq reveals the genetic structure and detects signals of selection in Italian brown trout.

BACKGROUND: Brown trout is one of the most widespread fresh-water fish species in Europe. The evolutionary history of and phylogenetic relationships between brown trout populations are complex, and this is especially true for Italian populations, which are heavily influenced in different ways by stocking practices. The characterization of the genetic structure of Italian brown trout populations may give information on the risk of losing endemic Italian populations due to lack of genetic diversity or to admixture with stocking populations. The identification of signatures of selection, and the information deriving from dense genotyping data will help genotype-informed breeding programs. We used a ddRAD-seq approach to obtain more than 100,000 single nucleotide polymorphisms (SNPs), and to characterize the population structure and signatures of selection in 90 brown trout samples. RESULTS: Italian brown trout populations are genetically differentiated, although the stocking practices have introduced strong admixture in endemic Italian trout, especially with the Atlantic lineage. Most of the analysed populations showed high levels of kinship and inbreeding. We detected putative signatures of selection using different approaches, and investigated if the regions were enriched for functional categories. Several regions putatively under selection and characterized by a reduction in heterozygosity across all the studied populations are enriched for genes involved in the response to viral infections. CONCLUSIONS: Our results, which show evidence of admixture with the Atlantic lineage (commonly used for stocking), confirm the need for controlling stocking practices, in order to avoid the erosion of the endemic gene pool; given the apparently high levels of kinship and inbreeding in local populations, our results also show the need to take action for increasing gene diversity. In addition, we used the genetically-distinct lineages to detect signatures of selection and we identified putative signatures of selection in several regions associated with resistance to infectious diseases. These constitute candidate regions for the study of resistance to infections in wild and farmed trout.

Perioperative Antibiotics and Other Factors Associated with Postcesarean Infections: A Case-Control Study.

OBJECTIVE: Our objective was to determine modifiable risk factors associated with surgical site infection (SSI) and postpartum endometritis. We hypothesized that inappropriate surgical antibiotic prophylaxis would be a risk factor for both types of infections. STUDY DESIGN: This was a single-center case-control study of SSI and endometritis after cesarean delivery over a 2-year period from 2016 to 2017. Cases were identified by International Classification of Diseases, 10th Revision diagnosis codes, infection control surveillance, and electronic medical records search and were subsequently confirmed by chart review. Three controls were randomly selected for each case from all cesareans ± 48 hours from case delivery. Demographic, pregnancy, and delivery characteristics were abstracted. Separate multivariable logistic regression models were used to assess factors associated with SSI and endometritis. Postpartum outcomes, including length of stay and readmission, were also compared. RESULTS: We identified 141 cases of SSI and endometritis with an overall postpartum infection rate of 4.0% among all cesarean deliveries. In adjusted analysis, factors associated with both SSI and endometritis were intrapartum delivery, classical or other (non-low-transverse) uterine incision, and blood transfusion. Factors associated with SSI only included inadequate antibiotic prophylaxis, public insurance, hypertensive disorder of pregnancy, and nonchlorhexidine abdominal preparation; factors only associated with endometritis included ß-lactam allergy, anticoagulation therapy, and chorioamnionitis. Among cases, 34% of those with SSI and 25% of those with endometritis did not receive adequate antibiotic prophylaxis, compared with 12.9 and 13.5% in control groups, respectively. Failure to receive appropriate antibiotic prophylaxis was associated with an increased risk of SSI (adjusted odds ratio [aOR]: 4.4, 95% confidence interval [CI]: 1.3-15.6) but not endometritis (aOR 0.9, 95% CI 0.4-2.0). CONCLUSION: Inadequate surgical antibiotic prophylaxis was associated with an increased risk of SSI but not postpartum endometritis, highlighting the different mechanisms of these infections and the importance of prioritizing adequate surgical prophylaxis. Additional potentially modifiable factors which emerged included blood transfusion and chlorhexidine skin preparation. KEY POINTS: · Inadequate antibiotic prophylaxis is associated with a four-fold risk in surgical site infections.. · The most common cause for failure to achieve adequate surgical prophylaxis was inappropriate timing of antibiotics at or after skin incision.. · Blood transfusions are strongly associated (>10-fold risk) with both SSI and endometritis..

The evolution of allergen-specific immunotherapy: The near and far future.

In the era of precision medicine, allergen immunotherapy (AIT) represents a landmark for the management of IgE-mediated allergic diseases. AIT is recognized as a potentially curative therapy and is currently accepted and routinely prescribed worldwide. However, there are still unmet needs. The efforts of researchers are aimed at implementing current immunotherapeutic strategies to improve the standard care of patients suffering from IgE-mediated respiratory allergic diseases. In addition, over the horizon, the most realistic option is the active treatment of IgE-mediated food allergy with oral immunotherapy. Preclinical studies and clinical trials are increasingly conducted to identify innovative forms of AIT administration, potential biomarkers, alternative immunotherapeutic allergen candidates, and new adjuvants. Telemedicine could represent a further emerging field capable of supporting health service delivery and improving clinical outcomes of AIT.

Early effects of first-line treatment with anti-interleukin-6 receptor antibody tocilizumab for chronic active antibody-mediated rejection in kidney transplantation.

INTRODUCTION: Chronic active antibody-mediated rejection (cAMR) is a major determinant of late allograft failure. Rituximab/immunoglobulins (IVIg) + plasma exchange (PLEX) showed controversial results in cAMR treatment. Tocilizumab (TCZ), a humanized anti-interleukin 6 receptor antibody, has been recently used as rescue therapy in patients non-responsive to rituximab/IVIg/PLEX with favorable outcomes. Whether TCZ acts "per se" or requires a priming effect from previous treatments is currently unknown. METHODS: Fifteen patients with cAMR were treated with TCZ as a first-line therapy and followed for a median time of 20.7 months. RESULTS: Despite the majority of patients experiencing advanced transplant glomerulopathy (TG) at diagnosis (60% with cg3), glomerular filtration rate and proteinuria stabilized during the follow-up, with a significant reduction in donor-specific antibodies. Protocol biopsies after 6 months demonstrated significant amelioration of microvascular inflammation and no TG, C4d deposition, or IF/TA progression. Gene-expression and immunofluorescence analysis showed upregulation of three genes (TJP-1, AKR1C3, and CASK) involved in podocyte, mesangial, and tubular restoration. CONCLUSION: Tocilizumab adopted as a first-line approach in cAMR was associated with early serological and histological improvements and functional stabilization even in advanced TG, suggesting a role for the use of TCZ alone with the avoidance of unnecessary previous immunosuppressants.

Pharmacokinetics and tissue disposition of enrofloxacin in rainbow trout after different routes of administration.

Plasma pharmacokinetics (PK) and tissue disposition of enrofloxacin (EFX) was studied in rainbow trout (Oncorhynchus mykiss) after a single oral administration of 10 mg/kg, and by immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, at water temperature of 16.3 ± 0.3 °C.Concentrations of EFX in plasma and tissues (skin, muscle, liver, kidney and gut) were determined using high performance liquid chromatography (HPLC) with fluorescence detection.Pharmacokinetic parameters were analyzed with a non-compartmental model. After oral administration, t½ß, AUC and AUCtissues/AUCplasma ratio were 42.98 h, 21.80µg-h/ml and ≤ 18.63, respectively.After immersion baths of 20 ppm during 2.5 h and 100 ppm during 0.5 h, the t½ß, AUC and AUCtissues/AUCplasma were 42.77 and 44.67, 9.83 and 12.83 µg-h/ml and ≤ 9.81 and ≤ 7.13, respectively.Therefore, oral (10 mg/kg) and bath administration in rainbow trout can provide AUC/MIC of ≥125 and Cmax/MIC of ≥10 to treat diseases caused by susceptible bacteria with MIC ≤ 0.04 µg/ml. This information can be helpful for the right use of EFX in rainbow trout. Also, this is the first study that determines the antibiotic tissue disposition in rainbow trout by using different administration routes.

Pharmacokinetics of levofloxacin after single intravenous and oral administration, and its interaction with sucralfate in mixed-breed dogs.

The study aims to establish the plasma pharmacokinetic parameters of levofloxacin in mixed-breed dogs, at a single dose of 5 mg/kg, intravenously, orally only and orally with sucralfate pre-treatment (1 g per animal), to evaluate its influence on antimicrobial absorption. Concentrations of levofloxacin in plasma were determined using high-performance liquid chromatography (HPLC) with fluorescence detection. After iv of levofloxacin, the mean (±SD) of AUC0-24, Vz, t½λz and MRT, was 19.05 ± 6.4 µg-h/ml, 2.43 ± 0.5 L/kg, 7.93 ± 1.41 hours and 8.7 ± 1.5 hours, respectively. After oral administration, the C max, t½λz and bioavailability were 1.95 ± 0.7 µg/ml, 7.65 ± 1.38 hours and 71.93 ± 9.75%, respectively. In animals given an oral dose of levofloxacin with sucralfate pre-treatment, there was a significant decrease (p < 0.05) in C max (0.57 ± 0.23 µg/ml), AUC (5.73 ± 2.26 µg-h/ml) and bioavailability (31.92 ± 14.19%). In the dogs studied, it is suggested that the dose 5 mg/kg of levofloxacin for both routes is inadequate to meet PK-PD targets for susceptible bacteria using breakpoints established by the Institute of Clinical and Laboratory Standards (CLSI).

Impact of natural menopause on multiple sclerosis: a multicentre study.

OBJECTIVE: To study the effect of natural menopause on multiple sclerosis clinical course. METHODS: This was an observational, retrospective, multicentre, cohort study. Menopause onset was defined by the final menstrual period (FMP) beyond which no menses occurred for 12 months. We included multiple sclerosis (MS) patients with FMP occurred after 2005 and a recorded follow-up of at least 2 years pre-FMP and post-FMP. We excluded patients with primary progressive course, iatrogenic menopause and with other confounders that could mask menopause onset. We compared relapse-rate and expanded disability status scale (EDSS) scores pre-FMP and post-FMP, searching for possible interactions with age, disease duration, cigarette smoking and nulliparity status. RESULTS: 148 patients were included (mean observation: 3.5 years pre-FMP and post-FMP). Most patients (92%) received disease-modifying therapies, mainly first-lines. After menopause the annualised relapse rate (ARR) significantly decreased (from 0.21±0.31 to 0.13± 0.24; p=0.005), while disability worsened (increase of mean 0.4 vs 0.2 points after menopause; p<0.001). Older age and long-lasting disease were associated with ARR reduction (p=0.013), but not with disability worsening. Cigarette smokers showed a trend to a higher disability accumulation after menopause (p=0.059). CONCLUSION: Natural menopause seems to be a turning point to a more progressive phase of MS. Relapse rate is also reduced after menopause, but this effect could be driven most by ageing and shifting to progressive phase in patients with long-lasting disease. Cigarette smoking could speed up disability progression after menopause.

Relationship between early proteinuria and long term outcome of kidney transplanted patients from different decades of donor age.

BACKGROUND: Proteinuria after kidney transplantation portends a worse graft survival. However the magnitude of proteinuria related to patient and graft survival and its correlation with donor and recipient characteristics are poorly explored. METHODS: This study investigated the impact of post transplant proteinuria in the first year in 1127 kidney transplants analyzing the impact of different donor ages. Proteinuria cut off was set at 0.5 g/day. RESULTS: Transplants with proteinuria > 0.5 g/day correlated with poor graft and patient outcome in all donor age groups. In addition, 6-month-1-year proteinuria increase was significantly associated with graft outcome, especially with donors > 60 years old (p < 0.05; Odd Ratio 1.8). 1-year graft function (eGFR < or ≥ 44 ml/min) had similar impact to proteinuria (≥ 0.5 g/day) on graft failure (Hazard Ratio 2.77 vs Hazard Ratio 2.46). Low-grade proteinuria (0.2-0.5 g/day) demonstrated a trend for worse graft survival with increasing donor age. Also in kidney-paired analysis proteinuria ≥0.5 effect was more significant with donors > 50 years old (Odd Ratio 2.3). CONCLUSIONS: Post-transplant proteinuria was increasingly harmful with older donor age. Proteinuria ≥0.5 g/day correlates with worse outcomes in all transplanted patients. Prognostic value of proteinuria and eGFR for graft and patient survival was comparable and these two variables remain significant risk factors even in a multivariate model that take into consideration the most important clinical variables (donor age, rejection, delayed graft function and cytomegalovirus viremia among others).

Half-dose fingolimod for treating relapsing-remitting multiple sclerosis: Observational study.

OBJECTIVES: To investigate the efficacy and safety of fingolimod (FTY) 0.5 mg administered every other day (FTY-EOD) compared to every day (FTY-ED) in multiple sclerosis patients. METHODS: Multicentre retrospective observational study. Clinical, laboratory and neuroimaging data were consecutively collected from 60 FTY-EOD and 63 FTY-ED patients. Baseline characteristics were compared using logistic regression. Efficacy in preventing occurrence of relapses and demyelinating lesions was tested using propensity score-adjusted Cox and linear regressions. RESULTS: Weight was inversely associated with risk of switch to FTY-EOD because of any reason (odds ratio (OR) = 0.94, 95% confidence interval (95% CI) = 0.89-0.99, p = 0.026), and female sex and lower baseline lymphocyte count were positively associated with switch because of lymphopenia. Compared to FTY-ED patients, FTY-EOD patients were at higher risk of developing relapses (hazard ratio (HR) = 2.98, 95% CI = 1.07-8.27, p = 0.036) and either relapses or new magnetic resonance imaging (MRI) demyelinating lesions (combined outcome, HR = 2.07, 95% CI = 1.06-4.08, p = 0.034). Within FTY-EOD, treatment with natalizumab before FTY and lower age were positively associated with risk of developing relapses and combined outcome, respectively (HR = 25.71, 95% CI = 3.03-217.57, p = 0.002 and HR = 0.85, 95% CI = 0.77-0.96, p = 0.005). FTY-EOD was overall well tolerated. CONCLUSION: Disease reactivation was observed in a significant proportion of patients treated with FTY-EOD. Neurologists should be cautious when reducing FTY administration to every other day, especially in younger patients and those previously treated with natalizumab.

Recurrent IgA nephropathy after renal transplantation and steroid withdrawal.

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis; the reported recurrence rate of IgAN after renal transplantation is as high as 13%-50%. The impact of immunosuppressive therapy and steroid withdrawal on the risk of recurrence of IgAN is still under debate. We performed a retrospective single-center study, selecting 123 kidney transplants (rtx) in 120 patients, between January 1995 and December 2012, with IgAN on the native kidney. In 51 of 123 transplants, at least one post-transplantation biopsy for clinical indication was performed; in 28 of 51 transplants, IgAN recurrence (IgANr) was demonstrated. This group (G1; N = 28) was compared with a group without IgANr (G2; N = 23). In our study, clinically evident IgANr rate was 54.9% (28/51) on biopsied patients. At discharge, the use of the immunosuppressant drugs (tacrolimus, cyclosporine A, mycophenolate mofetil, azathioprine, mTor inhibitors) was not associated with an increased risk of IgANr (P = NS). At discharge, all patients were steroid treated. Neither the use of tacrolimus, mycophenolate mofetil, nor mTor inhibitors (mTori) at biopsy time were associated with IgANr. However, IgANr was significantly higher in patients who experienced steroid withdrawal at any post-transplantation time (OR 7.7 P = .03). The median time to recurrence after steroid withdrawal was 59 months (min 4.18, max 113.2).

Detection of Angiotensin II type I-receptor antibodies in transplant glomerulopathy.

BACKGROUND: Transplant glomerulopathy (TG) is an important cause of late graft loss. The role of angiotensin type 1-receptor antibodies (AT1 R-Ab) in TG is not known. METHODS: All the TG cases (N = 137) between January 2007 and December 2014 (N = 1410) were analyzed. Donor-specific anti-HLA antibodies (DSA) at the time of biopsy and AT1 R-Ab IgG (positive, >17 UI/mL; "at risk," 10-17 UI/mL; negative, <10 UI/mL) in pre-transplant sera (PT-Ab) and at biopsy time (BT-Ab) were studied. RESULTS: AT1 R-PT-Ab+ and AT1 R-BT-Ab+ patients were 16.5% (51.5% "at risk") and 11.5% (27.4% "at risk"), respectively. Clinical correlations were found between AT1 R-Ab and HCV infection, number of transplants, and age. Considering Banff scores, ptc was higher in DSA+ patients vs AT1 R-PT-Ab+ (P = 0.002) or AT1 R-BT-Ab+ (P = 0.001) without differences in g and chronicity score (ci + ct); cg showed lower scores in DSA+ patients vs AT1 R-BT-Ab+ (P = 0.001). Graft survival was not influenced by the presence of AT1 R-Ab, AT1-R-Ab titer or MFI, but we observed a longer graft survival in patients with both AT1 R-BT-Ab+ or "at risk" and DSA+ vs patients positive only for DSA (P = 0.02), for AT1 R-BT-Ab (P = 0.019) or AT1 R-BT-Ab "at risk" (P = 0.039). CONCLUSION: AT1 R-Ab showed no independent prognostic role in TG in this pilot analysis.

Sulfide Species Optical Monitoring by a Miniaturized Silicon Photomultiplier.

The monitoring of water-soluble pollutants is receiving a growing interest from the scientific community. In this context, sulfide anion species S2- and HS- are particularly relevant since they can cause acute and chronic toxicity including neurological effects and at high concentrations, even death. In this study, a new strategy for fast and sensitive optical detection of sulfide species in water samples is described. The method uses an integrated silicon photomultiplier (SiPM) device coupled with the appropriate analytical strategy applied in a plastic microchip with dried reagents on board. More specifically, all sulfide species (H2S, HS- and S2-) in water samples are detected by the fluorescence signal emitted upon the reaction with N,N-dimethyl-phenylenediamine sulfate in the presence of Fe3+, leading to the formation of the fluorescent methylene blue (MB) species. It has been proven that the system herein proposed is able to measure sulfide concentration in a linear range from 0-10 mg L-1 with a sensitivity value of about 6.7 µA mg-1 L and a detection limit of 0.5 mg L-1. A comparison with conventional UV-Vis detection method has been also carried out. Data show a very good linear correlation (R² = 0.98093), proving the effectiveness of the method. Results pave the way toward the development of portable and low-cost device systems for water-soluble sulfide pollutants.

Pre-transplant assessment of CMV-specific immune response by Elispot assay in kidney transplant recipients.

Cytomegalovirus (CMV) primary infection or re-activation in solid organ transplant (SOT) recipients is associated with increased morbidity and mortality, with patients with IgG-CMV D+/R- sero-matching at greater risk. The impact of pre-transplant CMV-specific host cellular immunity on the long-term risk of CMV replication in kidney transplants (KT) was prospectively evaluated in eighty patients by CMV-EliSpot assay. The study population included 54 male and 26 female recipients, with CMV-IgG distribution: 60 D+/R+, 11 D-/R+, 7 D+/R-, 2 D-/R-. At pre-transplantation, 49 KT (61.3%) were CMV-responders by EliSpot. At 3-month follow up, 16 (32.7%) out of 49 CMV-responders showed CMV blood infection, compared to 8 (25.8%) out of 31 non-responders. No further episode of CMV viraemia was reported in the responder group, in comparison to 15 out 31 non-responders (48.4%) showing at least one episode of CMV-DNAemia at 12-month follow-up. Baseline CMV-IgG serology showed a strong correlation with EliSpot determinations; KT recipients exhibiting at least one episode of CMV viraemia at 12-month follow-up showed lower baseline CMV-EliSpot values than those without signs of CMV replication. The study suggests that monitoring CMV-specific T-cell responses at pre-transplantation by EliSpot assay may be useful for predicting the post-transplantation risk of CMV infection and reactivation.

Perceived challenges and attitudes to regimen and product selection from Italian haemophilia treaters: the 2013 AICE survey.

Despite great advances in haemophilia care in the last 20 years, a number of questions on haemophilia therapy remain unanswered. These debated issues primarily involve the choice of the product type (plasma-derived vs. recombinant) for patients with different characteristics: specifically, if they were infected by blood-borne virus infections, and if they bear high or low risk of inhibitor development. In addition, the most appropriate treatment regimen in non-inhibitor and inhibitor patients compel physicians operating at the haemophilia treatment centres (HTCs) to take important therapeutic decisions, which are often based on their personal clinical experience rather than on evidence-based recommendations from published literature data. To know the opinion on the most controversial aspects in haemophilia care of Italian expert physicians, who are responsible for common clinical practice and therapeutic decisions, we have conducted a survey among the Directors of HTCs affiliated to the Italian Association of Haemophilia Centres (AICE). A questionnaire, consisting of 19 questions covering the most important topics related to haemophilia treatment, was sent to the Directors of all 52 Italian HTCs. Forty Directors out of 52 (76.9%) responded, accounting for the large majority of HTCs affiliated to the AICE throughout Italy. The results of this survey provide for the first time a picture of the attitudes towards clotting factor concentrate use and product selection of clinicians working at Italian HTCs.

4A syndrome: ocular surface investigation in an Italian young patient.

BACKGROUND: Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. CASE PRESENTATION: An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. CONCLUSIONS: The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

An Evaluation of Hemostatic Dysregulation in Canine Multicentric Lymphoma.

Multiple hemostatic abnormalities are associated with paraneoplastic syndrome and some malignant tumors. Lymphoma is the most common hematopoietic neoplasm in dogs, sometimes associated with hemostatic changes. The objectives of this study were to evaluate the behavior of coagulation parameters in dogs with multicentric lymphoma compared with diseased dogs without lymphoma, to separately evaluate the effect of immunophenotype (B lymphoma versus T lymphoma) on the variables of interest as well as the effect of disease stage (stage II to IV versus stage V). Specifically, a cross-sectional study was performed with a matched comparison group considering 170 dogs with B or T lymphoma (group 1) and 170 dogs with no lymphoma or other neoplastic processes but other diseases (group 0). Eight coagulation parameters were evaluated: platelet count (Plt), activated partial thromboplastin time (aPTT), prothrombin time (PT), thrombin time (TT), fibrinogen, fibrin/products of fibrinogen degradation (FDPs), fibrin D-dimers, and antithrombin (AT). Dogs with lymphoma showed prolonged PT and TT, decreased fibrinogen, increased FDP, and decreased Plt compared with group 0. The effect of disease stage was evaluated separately for dogs with stage II to IV lymphoma and dogs with stage V lymphoma; patients with stage II-IV lymphoma showed no significant differences, while in dogs with stage V lymphoma, a prolongation of PT and TT, a decrease in fibrinogen, an increase in FDPs and a decrease in Plt were found compared with the group 0. Finally, the comparison between B lymphoma and T lymphoma showed no significant differences in coagulation parameters between the two groups. Logistic regression analysis demonstrated that low fibrinogen and platelet levels were the most significant predictors of lymphoma in a cohort of canine patients. These hemostatic abnormalities in lymphoma appeared to be associated with the stage of the disease rather than the lymphoma immunophenotype. These findings pave the way for the possible scenario of lymphoma-associated fibrinolysis and the so far undescribed pattern of hyperfibrinolysis associated with the most severe stage of lymphoma.

Entire papilla preservation technique for treatment of periodontal intrabony defects: a series of cases.

OBJECTIVE: Periodontitis is characterized by bone resorption. Vertical bone loss results in an intraosseous defect. Multiple surgical approaches for treating intrabony defects have shown different grades of effectiveness. Recently, the entire papilla preservation technique has been proposed, improving clinical parameters, such as pocket depth and clinical attachment level. This series of cases aimed to describe the use of the entire papilla preservation surgical technique without using biomaterials to regenerate periodontal intrabony defects. The influence on the clinical periodontal parameters and radiographic parameters was measured through CBCT, the latter not described until now, and analyzed the possible postoperative complications. METHOD AND MATERIALS: A total of six intrabony periodontal defects associated with at least one periodontal pocket with probing depths equal to or greater than 6 mm were treated with the entire papilla preservation technique. The clinical and radiographic parameters were evaluated at the beginning and 6 months after surgery. RESULTS: The mean probing pocket depth reduction was 4.00 ± 0.63 mm, the mean clinical attachment level gain was 3.67 ± 1.03 mm, and the mean radiographic intrabony filling was 2.41 ± 2.03 mm. Early healing was uneventful; the mean visual analog scale at 7 days was 0. CONCLUSIONS: This minimally invasive technique results in an improvement in clinical and radiographic parameters, the latter showing a filling of the bone defect observed during the 6-month evaluation after surgical treatment. These results confirm the importance of clot and flap stability in regenerating intraosseous defects.