LRP1/CD91 is up-regulated in monocytes from patients with haemophilia A: a single-centre analysis.

The low-density lipoprotein receptor-related protein 1 (LRP1) is an ubiquitously expressed endocytic receptor that, among its several functions, is involved in the catabolism of coagulation factor VIII (FVIII) and in the regulation of its plasma concentrations. Although LRP1/CD91 polymorphisms have been associated with increased FVIII levels and a consequent thrombotic risk, no data are available on LRP1/CD91 expression in patients with inherited FVIII deficiency. With the aim of elucidating this issue, 45 consecutive patients with haemophilia A (HA) (18 severe, 5 moderate and 22 mild HA) were enrolled in this cross-sectional, single-centre survey. The LRP1/CD91 mean fluorescence intensity (MFI) in monocytes from HA patients was significantly higher than that detected in 90 healthy blood donors (105 vs. 67, P < 0.001). This over-expression was independent of hepatitis C virus infection status and varied according to the severity of the haemophilia, being higher in patients with more severe FVIII deficiency. In conclusion, our study documents for the first time that LRP1/CD91 is over-expressed on monocytes from HA patients, with the intensity of expression varying according to the severity of the FVIII deficiency. Further studies are needed to assess the clinical implications of these findings.

Determination of normative values for 20 min exercise of wheelchair propulsion by spinal cord injury patients.

STUDY DESIGN: This was a retrospective observational study. OBJECTIVE: The objective was to determine the normative values for 20 min exercise of wheelchair propulsion in spinal cord injury (SCI) subjects. SETTING: Sarah Rehabilitation Hospitals Network, Brazil. METHODS: A total of 413 medical records for SCI patients at different levels and classifications at the Sarah Rehabilitation Hospitals Network, Brazil, who performed 20 min exercise in a rehabilitation programme between the years 2004 and 2009 were consulted. Information regarding patient and performance characteristics was obtained, including distance travelled, mean velocity, rest and exercising heart rate and perceived exertion. The data were analysed by gender and by injury level group: tetraplegia (TT) or paraplegia (PP). RESULTS: The participants' ages ranged from 18 to 64 years, and the median time since injury was 1.2 years. The men and women had different performances regardless of their level of injury. The distance ranged between 495 and 2106 m for men and between 300 and 1901 m for women. The mean velocity of propulsion ranged from 25 to 105 m min(-1) for men and from 15 to 95 m min(-1) for women. CONCLUSIONS: This study provides normative data for the 20 min exercise that could be used to estimate the resistance capacity by manual wheelchair users with SCI and evaluate the effects of training and other therapeutic interventions.

Total Worker Health®: knowledge of a sample of Occupational Physicians and Prevention and Protection Service Managers.

Background: In the workplace, it is increasingly important to promote interventions to improve the work environment that can combine compliance with regulations related to worker health and safety protection with health promotion interventions. The objective of our study is to investigate the status of the implementation of various health management measures through questionnaires submitted to Occupational Physicians (OPs) and Prevention and Protection Service Managers (PPSMs). Methods: This study was conducted between September 2022 and November 2022. Healthcare professionals were invited to voluntarily answer the questions, administered through a Google form, of a standardized questionnaire (Cronbach's alpha=0.887) based on the study made by Hoge et al. (2019): the first part collected demographic information and the other four were relating to the state of implementation of interventions attributable to the Total Worker Health® approach. Results: 89 OPs and PPSMs were involved. The univariate and multivariate analysis shows that, overall, women and PPSMs have a higher degree of dissatisfaction related to various health management measures within companies; most workers are fairly satisfied with health and safety protection in the workplace; finally, according to healthcare professionals, aspects of primary prevention and work management/organization would need to be improved. Conclusions: This study shows that in Italian companies there is often no full application of Total Worker Health® principles. The affirmation of this approach, awareness should be raised, first and foremost, among employers, but also among prevention figures and consultants about all the benefits of Total Worker Health®: one among all, an 'economic' advantage.

The natural history of mild haemophilia: a 30-year single centre experience.

Although up to 50% of all haemophilic patients followed at haemophilia treatment centres (HTCs) are affected by a mild factor VIII (FVIII) or factor IX (FIX) defect, published data regarding the natural history of these disorders are scarce. To fill this lack of information, a retrospective single centre study was conducted. All cases with mild haemophilia (75 A and 7 B) followed at the regional reference HTC of Parma were evaluated. The patients' median age at diagnosis was 11.5 years and their median age at first bleeding was 5.5 years; 95% of patients had a history of haemorrhagic problems during their life. Twenty-three percent of patients were infected by HCV, and none by HIV. Genetic analysis was performed in 80 patients (97% haemophilia A and 100% haemophilia B) and 21 different mutations were characterized. Eleven percent of patients had never received treatment, whereas 67% were treated with plasma-derived or recombinant FVIII/FIX concentrates (4% developed inhibitors). desmopressin (DDAVP) was used in 80% of the haemophilia A patients. The response to DDAVP was closely related to the patients' genetic profile, as 60% of non-responders had a mutation in the F8 promoter region. Patients with mild haemophilia may experience a variety of medical problems, sometimes challenging for the physicians, during their lifetime. The HTCs play an important role in the management of these patients, whose diagnosis is often delayed. The HTCs should improve patients' knowledge and consideration of their disease and encourage them to maintain regular contact with their haemophilia care provider.

Trophic ecology of northern Australia's terapontids: ontogenetic dietary shifts and feeding classification.

The diets of 21 terapontid species from freshwater environments in northern Australia were investigated to determine the similarity and dissimilarity among species and the extent of any ontogenetic shifts. Distinct ontogenetic dietary shifts occurred in all species for which sufficient data were available, with many species passing through several discrete trophic categories during their life histories. Diets of all juvenile terapontids were similar, mainly comprising aquatic insects and zooplankton. Larger size classes of terapontids diverged into a broad spectrum of feeding groups comprising carnivorous dietary modes (including piscivory and lepidophagy), omnivory (including frugivory and consumption of allochthonous prey), herbivory and detritivory. The results indicate that the terapontids represent Australia's most trophically diverse freshwater fish family.

Is the elusive Gymnothorax polyuranodon really a freshwater moray?

Analysis of 36 records of the rarely encountered moray Gymnothorax polyuranodon indicate that juveniles and adults inhabit fresh and mildly brackish habitats (salinity < 5) in streams of the Australian Wet Tropics Eighty-one per cent of these records were from freshwater streams and collectively demonstrate that this species inhabits fresh water throughout all seasons. A survey of fish researchers, each with at least 100 h of field experience in Australia's Wet Tropics, revealed that 33% of researchers working in fresh waters (nine of 27 researchers) had encountered the species and 15% of researchers with substantial experience working in estuaries (two of 13 researchers) had encountered the species. The species was not sampled or observed in the nearshore marine environment. The only record of an elver of this species was, however, found in an estuary at a salinity of 33·4. This preliminary evidence suggests adult G. polyuranodon occupy freshwater habitats, but further research is required to understand the complete life cycle, including movements, habitat use and reproductive ecology of the species.

Effectiveness of chondroitin sulphate in patients with concomitant knee osteoarthritis and psoriasis: a randomized, double-blind, placebo-controlled study.

OBJECTIVE: The aim of the trial was to assess the efficacy of chondroitin sulphate (CS) on symptomatic knee osteoarthritis (OA) associated to psoriasis. METHODS: In this randomized, double-blind, placebo (PBO)-controlled clinical trial 129 patients with symptomatic knee OA and concomitant psoriasis were randomized into two groups receiving 800 mg daily of CS or PBO for 3 months. The primary efficacy outcome for knee OA was the Huskisson's visual analogue scale (VAS) and for psoriasis was the Psoriasis Area and Severity Index (PASI). Additionally, other secondary efficacy criteria for both conditions were assessed. RESULTS: After 3 months of treatment, CS was more effective than PBO, relieving pain VAS (CS -26.9+/-24.8 vs PBO -14.23+/-20.8mm, P<0.01), decreasing the Lequesne index (CS -4.8+/-3.4 vs PBO -3.3+/-3.5, P<0.05) and reducing the number of patients using acetaminophen as rescue medication (CS 43% vs PBO 64%, P<0.05). Regarding PASI, Overall Lesion Severity Scale and Physician's Global Assessment of Change no statistically significant changes were detected in front of PBO. However, CS improved plantar psoriasis compared to PBO (CS 87% vs PBO 27%, P<0.05). Quality of life improved significantly in CS-treated patients according to the Short Form-36 health survey and the Dermatology Life Quality Index (DLQI). CS tolerability was excellent. Adverse events were infrequent and evenly distributed among groups. The incidence of psoriatic flares did not increase after treatments. CONCLUSIONS: This study confirms the efficacy and safety of CS as a symptomatic slow-acting drug in patients with knee OA and shows that CS improves plantar psoriasis. The use of CS could represent a special benefit in patients with both pathologies since non-steroidal anti-inflammatory drugs have been reported to induce or exacerbate psoriasis.

Spectrum of F8 gene mutations in haemophilia A patients from a region of Italy: identification of 23 new mutations.

SUMMARY: Haemophilia A (HA) is an X-linked recessive bleeding disorder caused by a lack or decrease of coagulation factor VIII activity. The molecular diagnosis of HA is challenging and a variety of different mutations have been identified throughout the F8 gene. Our aim was to detect the causative mutation in 266 HA patients from Emilia-Romagna region (Italy) and in all suspected carriers. Molecular analysis of F8 in 201 HA patients (152 index cases) was performed with a combination of several indirect and direct molecular approaches, such as long distance polymerase chain reaction, multiplex ligation-dependent probe amplification, denaturing high performance liquid chromatography and direct sequencing. The analysis revealed 78 different mutations, 23 of which were novel, not having been reported in national or international databases. The detection rate was 100%, 86% and 89% in patients with severe, moderate and mild HA, respectively. The information provided by this registry will be helpful for monitoring the treatment of HA patients in Emilia-Romagna and also for reliable genetic counselling of affected families in the future.

Mortality and causes of death in Italian persons with haemophilia, 1990-2007.

Although a number of studies have analysed so far the causes of death and the life expectancy in haemophilic populations, no investigations have been conducted among Italian haemophilia centres. Thus, the aim of this study was to investigate mortality, causes of deaths, life expectancy and co-morbidities in Italian persons with haemophilia (PWH). Data pertaining to a total of 443 PWH who died between 1980 and 2007 were retrospectively collected in the 30 centres who are members of the Italian Association of Haemophilia Centres that chose to participate. The mortality rate ratio standardized to the male Italian population (SMR) was reduced during the periods 1990-1999 and 2000-2007 such that during the latter, death rate overlapped that of the general population (SMR 1990-1999: 1.98 95% CI 1.54-2.51; SMR 2000-2007: 1.08 95% CI 0.83-1.40). Similarly, life expectancy in the whole haemophilic population increased in the same period (71.2 years in 2000-2007 vs. 64.0 in 1990-1999), approaching that of the general male population. While human immunodeficiency virus infection was the main cause of death (45%), 13% of deaths were caused by hepatitis C-associated complications. The results of this retrospective study show that in Italian PWH improvements in the quality of treatment and global medical care provided by specialized haemophilia centres resulted in a significantly increased life expectancy.

A web-based clinical record 'xl'Emofilia' for outpatients with haemophilia and allied disorders in the Region of Emilia-Romagna: features and pilot use.

The treatment of haemophilia in developed countries is based on home self-infusion of concentrates. Improving communication between haemophilia centres (HC) and patients is very important. The Hub Centre (Parma) designed a new outpatient clinical record, 'xl'Emofilia', as part of a project 'Web Connections of the Region's HC' funded by Emilia-Romagna Health Authority. It is a web-based application suited to the needs of HC, which shares the databases of the region's HC, integrated with regional and national registries that can be accessed from anywhere. Data are managed with the 'https' protocol. Significant innovations are 'pathways' that help with the entry of data and 'problem list', which is a summary (updated automatically) of the patient's clinically significant data that can be consulted at a glance. With a 'web identity' (a personal USB key for secure web access), patients can record bleeds and home infusions, consult their own data and allow access to their general practitioners or in emergency departments anywhere in the world (also in English language). In December 2006, the HC started to use 'xl'Emofilia' and 673 clinical records are now active. Since April 2007, 50 pilot patients have been trained and are successfully using the system. A questionnaire administered to these patients on their level of satisfaction with the system and its ease of use gave excellent results. Our web-based system facilitates communication between patients and HC, improves the quality of care and enables patients to use these information at any time and from anywhere in the world.

Comparative Analysis of Clinical Outcomes and Procedural Costs between the Conventional Two-stage Technique and 4D Brachytherapy for Early Prostate Cancer.

AIMS: To assess long-term outcomes and resource use of 4D Brachytherapy, a one-stage real-time implant for the treatment of prostate cancer that uses stranded and loose iodine-125 seeds, and to compare with the conventional two-stage (2S) technique. MATERIALS AND METHODS: Prospectively collected data of men who underwent 2S and 4D low dose rate brachytherapy in a single institution were analysed. Survival estimates were analysed using the Kaplan-Meier method and Log-rank test. Treatment failure rates were further compared by Cox proportional hazards (Coxph) regression or by a surrogate prostate-specific antigen value cut-off of 0.4 ng/ml 48 months post-implant. Treatment toxicity outcomes were also evaluated. Comparative costs were based on published English National Health Service data. RESULTS: We compared outcomes of 690 men treated with 2S and 1031 men with 4D brachytherapy. Median follow-up times were 10.4 and 5.2 years (P < 0.001) for 2S and 4D cases, respectively. Day 0 post-implant dosimetry was improved in 4D brachytherapy patients. Five years post-implant ≥98% of cases were alive and ≥95% were free from disease relapse irrespective of technique. Coxph regression showed the risk of relapse after 4D brachytherapy was similar to the 2S technique (hazard ratio 0.67, 95% confidence interval 0.44-1.03, P = 0.065). Forty-eight months post-implant there was a significantly greater proportion of 4D brachytherapy cases with a prostate-specific antigen below 0.4 ng/ml relative to the 2S technique. Urinary and bowel symptom scores showed reduced toxicity after 4D implants and potency conservation was similar to the 2S technique. The reduction in time and resource use decreased the cost of 4D brachytherapy by 40% compared with the 2S technique. CONCLUSION: Two-stage and 4D brachytherapy are both highly effective for the control of localised prostate cancer. However, relative to the 2S technique, the 4D technique was associated with improved dosimetry, reduced treatment-related toxicity and reduced cost. Further follow-up will assess disease control superiority of 4D brachytherapy beyond 5 years post-implant.

Pelvic Organ Motion during Radiotherapy for Cervical Cancer: Understanding Patterns and Recommended Patient Preparation.

AIMS: Minimisation of organ position variation during pelvic radiotherapy is vital for accurate treatment. We analysed bladder and rectal filling during radiotherapy to understand variation reduction methods. MATERIALS AND METHODS: Cone beam computed tomography scans (CBCTs) taken twice weekly during three-dimensional conformal radiotherapy were retrospectively analysed for 10 cervical cancer patients. Bladder and bowel preparation was followed. Two independent clinicians outlined bladder, rectum and the primary clinical target volume (CTV) on each CBCT. Effects of time, chemotherapy and drinking time on bladder and rectal volume were analysed. CTV coverage impact was investigated using fixed effect logistic regression modelling. RESULTS: Ten planning scans and 109 CBCTs were reviewed. The bladder volume was 45-578 cm(3) during radiotherapy and 73-664 cm(3) at planning. The bladder volume increased (4 cm(3)/min) with waiting time, decreased (average 4 cm(3)/day) through treatment and was larger (about 50 cm(3)) after chemotherapy. A bladder volume difference > 130 cm(3) from planning led to the planning target volume (PTV) not covering the CTV. The probability of the PTV covering the CTV for every cm(3) deviation from the planning volume reduced by 1.9%, predominantly affecting the uterus. Planning bladder volumes > 300 cm(3) were not reproducible during treatment. The rectal anterior-posterior diameter correlated with volume. No pattern was displayed through treatment. The probability of the PTV covering the CTV with every mm deviation from the planning anterior-posterior diameter reduced by 5.8%, predominantly affecting the cervix. The risk of the PTV not covering the CTV is higher if the rectum is larger during treatment than planning. As bladder volume decreased rectal anterior-posterior diameter increased. CONCLUSION: Our data suggest an ideal planning bladder volume of 150-300 cm(3), a shorter waiting time on post-chemotherapy days and adequate hydration throughout treatment. Laxatives at planning and throughout treatment may also be beneficial. Even with these measures, regular imaging is vital when implementing advanced radiotherapy techniques for gynaecological cancers.

Tissue models of peritoneal fibrosis.

OBJECTIVE: To evaluate the utility of peritoneal pathologic samples, unrelated to peritoneal dialysis (PD) treatment, for the study of peritoneal fibrosis and inflammation. METHODS: Comparative morphologic and immunohistochemical study of peritoneal pathologic samples unrelated to PD with peritoneal biopsies from PD patients with special emphasis on the expression of myofibroblastic and epithelial-to-mesenchymal transition markers. RESULTS: Regarding morphology, PD-related simple fibrosis was less cellular, with greater stromal hyalinization, determining a homogeneous, hypocellular aspect of the submesothelium. In contrast, non-PD fibrosis was more cellular with an extracellular matrix showing a dense and fibrillar quality with wide bundles of collagen. Hylinazing vasculopathy was only present in PD samples. Myofibroblastic differentiation and epithelial-to-mesenchymal transition were common findings in all situations of peritoneal fibrosis. Calponin and calretinin are useful cellular markers to study such fibrogenic mechanisms and correlate with other well-known markers such as a -SMA and cytokeratins. Their expression was much more intense in those samples showing acute inflammation (peritonitis). CONCLUSIONS: Non-PD models of peritoneal fibrosis seem very useful to evaluate important features of human peritoneal pathology such us fibrogenesis, and inflammation. Fibrogenic events such as myofibroblastic differentiation and epithelial-to-mesenchymal transition are evident in these tissue samples allowing us to use them as an accessible source for in vivo and ex vivo studies. Both events show their maximal expression in situations of acute inflammation supporting the important role that peritonitis episodes play in the progression of fibrosis.

Severe gastrointestinal bleeding in a uremic patient treated with estrogen-progesterone therapy.

Gastrointestinal bleeding is a frequent complication in hemodialysis patients; angiodysplasia is a potential cause, with a higher incidence in uremic patients. We describe a case of severe anemia (Hemoglobin up to 3.5 g/dl) secondary to diffuse angiodysplastic lesions in a hemodialysis patient with mixed connective tissue disease. The case is characterised both by the severity of the clinical picture (extension and entity of angiodysplastic lesions, frequency of bleeding episodes) and by the patient's religious faith which made her reject blood transfusions. We underline the efficacy of estrogen-progesterone therapy in view of the modest results obtained with other therapeutic strategies on bleeding.

Effects of dialysis membrane nature on intradialytic phagocytizing activity.

Blood-membrane contact in the extracorporeal circuit affects the activation of many biological systems. Among these, phagocytizing activity has been reported to be influenced by the nature of the hemodialysis membrane used, whether cellulosic or synthetic. This work reports on an ex-vivo, comparative test between cellulosics and synthetics concerning the effects of blood-membrane contact on the polymorphonucleate and monocyte phagocytizing function, both during and after the hemodialysis session. By means of flow cytometry, we evaluated the capacity for phagosoma formation and oxidative burst both in polymorphonucleates and monocytes. Ten hemodialysis patients were included in the study. Six separate dialysis procedures for each patient were considered, one per dialyzer (3 cellulosic and 3 synthetic membranes). Tests were performed at 15', 60', 210' and 4 hours after the session end. Comparative evaluation was made according to Student's t test. Polymorphonucleate phagocytosis and oxidative burst activation were globally more marked for synthetic than cellulosic membranes, tending to level out in the post-dialysis. This result could be affected by their functional exhaustion following pulmonary sequestration. Monocyte intradialytic phagocytosis and oxidative burst proved more activated by cellulosic membrane. All differences tended to vanish in the post-dialysis.

[Isolated laryngeal candidiasis. Description of 2 cases and review of the literature]. / Candidiasis laríngea aislada. Descripción de 2 casos y revisión de la literatura.

Infection of the larynx by Candida is rare and usually accompanies lung or disseminated candidiasis. The incidence of isolated laryngeal candidiasis (ILC) is low, although it may be underestimated. We describe 2 patients with ILC confirmed during autopsy: a 45-years-old male with pulmonary fibrosis and a 4-years-old girl with acute myeloblastic leukemia. Hoarseness and dysphagia are the most common symptoms of ILC. The most effective diagnostic technique is laryngoscopy with specimen culture and/or histopathology. Specimens usually show whitish plaques on the larynx. Most ILC patients have some associated disease and/or predisposing factors, with frequent antibiotic treatment prior to the advent of candidiasis. Intravenous amphotericin B provides the most effective therapy, although other antimycotics are also useful. Early diagnosis and initiation of therapy curtail the disease and can prevent systemic dissemination.