Search

DYT1 dystonia is a debilitating neurological movement disorder arising from mutation in the AAA+ ATPase TorsinA. The hallmark of Torsin dysfunction is nuclear envelope blebbing resulting from defects in nuclear pore complex biogenesis. Whether blebs actively contribute to disease manifestation is unknown. We report that FG-nucleoporins in the bleb lumen form aberrant condensates and contribute to DYT1 dystonia by provoking two proteotoxic insults. Short-lived ubiquitylated proteins that are normally rapidly degraded partition into the bleb lumen and become stabilized. In addition, blebs selectively sequester a specific HSP40-HSP70 chaperone network that is modulated by the bleb component MLF2. MLF2 suppresses the ectopic accumulation of FG-nucleoporins and modulates the selective properties and size of condensates in vitro. Our study identifies dual mechanisms of proteotoxicity in the context of condensate formation and establishes FG-nucleoporin-directed activities for a nuclear chaperone network.

This article aims to show the usefulness of the pneumo-computed tomography gastric distention technique in the detection and morphological characterization of subepithelial gastric lesions. We correlate the pneumo-computed tomography and pathology findings in lesions studied at our institution and review the relevant literature.Pneumo-computed tomography, combined with multiplanar reconstructions, three-dimensional reconstructions, and virtual endoscopy, is useful for delineating the morphological details of subepithelial gastric lesions, thanks to the additional gastric distention. This technique better delimits and characterizes the upper and lower margins of the lesions. Pneumo-computed tomography can be considered a useful noninvasive imaging techniques for characterizing these lesions.

The lung exhibits a robust, multifaceted regenerative response to severe injuries such as influenza infection, during which quiescent lung-resident epithelial progenitors participate in two distinct reparative pathways: functionally beneficial regeneration via alveolar type 2 (AT2) cell proliferation and differentiation, and dysplastic tissue remodeling via intrapulmonary airway-resident basal p63

Prion protein (PrP) concentration controls the kinetics of prion replication and is a genetically and pharmacologically validated therapeutic target for prion disease. In order to evaluate PrP concentration as a pharmacodynamic biomarker and assess its contribution to known prion disease risk factors, we developed and validated a plate-based immunoassay reactive for PrP across 6 species of interest and applicable to brain and cerebrospinal fluid (CSF). PrP concentration varied dramatically across different brain regions in mice, cynomolgus macaques, and humans. PrP expression did not appear to contribute to the known risk factors of age, sex, or common PRNP genetic variants. CSF PrP was lowered in the presence of rare pathogenic PRNP variants, with heterozygous carriers of P102L displaying 55%, and D178N just 31%, of the CSF PrP concentration of mutation-negative controls. In rodents, pharmacologic reduction of brain Prnp RNA was reflected in brain parenchyma PrP and, in turn in CSF PrP, validating CSF as a sampling compartment for the effect of PrP-lowering therapy. Our findings support the use of CSF PrP as a pharmacodynamic biomarker for PrP-lowering drugs and suggest that relative reduction from individual baseline CSF PrP concentration may be an appropriate marker for target engagement.

DYT1 dystonia is a debilitating neurological movement disorder arising from mutation in the AAA+ ATPase TorsinA. The hallmark of Torsin dysfunction is nuclear envelope blebbing resulting from defects in nuclear pore complex biogenesis. Whether blebs actively contribute to disease manifestation is unknown. We report that FG-nucleoporins in the bleb lumen form aberrant condensates and contribute to DYT1 dystonia by provoking two proteotoxic insults. Short-lived ubiquitylated proteins that are normally rapidly degraded partition into the bleb lumen and become stabilized. In addition, blebs selectively sequester a specific HSP40-HSP70 chaperone network that is modulated by the bleb component MLF2. MLF2 suppresses the ectopic accumulation of FG-nucleoporins and modulates the selective properties and size of condensates in vitro. Our study identifies dual mechanisms of proteotoxicity in the context of condensate formation and establishes FG-nucleoporin-directed activities for a nuclear chaperone network.

Neurons transmit and receive information at specialized junctions called synapses. Excitatory synapses form at the junction between a presynaptic axon terminal and a postsynaptic dendritic spine. Supporting the shape and function of these junctions is a complex network of actin filaments and its regulators. Advances in microscopic techniques have enabled studies of the organization of actin at synapses and its dynamic regulation. In addition to highlighting recent advances in the field, we will provide a brief historical perspective of the understanding of synaptic actin at the synapse. We will also highlight key neuronal functions regulated by actin, including organization of proteins in the pre- and post- synaptic compartments and endocytosis of ion channels. We review the evidence that synapses contain distinct actin pools that differ in their localization and dynamic behaviors and discuss key functions for these actin pools. Finally, whole exome sequencing of humans with neurodevelopmental and psychiatric disorders has identified synaptic actin regulators as key disease risk genes. We briefly summarize how genetic variants in these genes impact neurotransmission via their impact on synaptic actin.

Interaction between the motor and nociceptive systems seems to play an important role in chronic pain. In this pilot study we used a combination of functional near-infrared spectroscopy (FNIRS) and laserevoked potentials (LEPs) during concurrent finger tapping task and noxious laser stimulation in fibromyalgia (FM) patients and controls. The study included 9 healthy subjects and 15 FM patients. During concurrent FNIRS and LEP recording, participants were required either to remain in resting relaxed condition or to execute a finger tapping task with the right hand. In the control group, the left motor cortex showed increased oxyhaemoglobin levels, while the early N1 LEP component was reduced, during the finger tapping task. In FM patients, motor cortex oxyhaemoglobin concentrations were lower during movement, which did not reduce LEPs. The left motor cortex oxyhaemoglobin concentrations had 79.2% diagnostic accuracy. The interplay between motor and pain-related circuits seems to be dysfunctional in FM patients. These results may support a role for motor cortex modulation in the treatment of this disabling disease.

Rehabilitation therapy is an important aspect of recovery after volumetric muscle loss. However, the traditional rehabilitation approach involves a period of rest and passive loading followed by gradual active loading. Extracellular matrix is a naturally occurring material consisting of structural proteins that provide mechanical strength, structural support, and functional molecules with diverse bioactive properties. There is evidence to suggest that the addition of aggressive regenerative rehabilitation protocols immediately after surgical implantation of an extracellular matrix scaffold to an area of volumetric muscle loss has significant benefits for extracellular matrix remodeling. Rehabilitation exercises likely provide the needed mechanical signals to encourage cell migration and site-specific differentiation in the temporal framework required for constructive remodeling. Herein, the authors review the literature and present an example of an aggressive rehabilitation program implemented immediately after extracellular matrix transplantation into a severely injured quadriceps muscle.

The 1995 Peritoneal Dialysis Core Indicators Study was conducted by the Health Care Financing Administration to ascertain standard practices and outcomes in chronic peritoneal dialysis patients. Data from 1,202 patients who did not receive hemodialysis but who were on chronic ambulatory peritoneal dialysis (CAPD) for at least part of the 6-month period between November 1, 1994, and April 30, 1995, are reported. The mean serum albumin level for this cohort was 3.5 g/dL by the bromcresol green method and 3.2 g/dL by the bromcresol purple method. Data sufficient to calculate a weekly Kt/V urea or weekly creatinine clearance were available for only 34% of patient submissions. In these patients, the median weekly Kt/V urea was 1.7 using a fixed value for V of 0.58 × body weight and was 2.0 using the Watson equation to calculate V, the median weekly creatinine clearance was 60.7 L/wk/1.73 m 2 . The mean hematocrit for this cohort was 32% and the average weekly recombinant human erythropoietin (rHmEPO) dose was 115 μ/ kg. Hematocrit values ≤30% were found in 50% of black patients and 31% of white patients. The average blood pressure among peritoneal dialysis patients was 139/80 mm Hg, with 29% of patients having a systolic blood pressure exceeding 150 mm Hg and 18% a diastolic blood pressure greater than 90 mm Hg. In summary, serum albumin levels were significantly lower in peritoneal dialysis patients than in hemodialysis patients. Approximately one third of peritoneal dialysis patients did not have an adequacy measure obtained during the 6-month observation period. A significant minority of patients had either inadequately treated anemia of chronic renal disease or hypertension. There is an opportunity to substantially improve the medical care provided to chronic peritoneal dialysis patients.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Rof eron-A, Roche) (n=12) or placebo (n=8) every other day for 6 months and followed up for a further 6 months after stopping treatment Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect prof ile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type 1 interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type 1 IFN therapy.

Ectopic artery calcification has been documented in women with postmenopausal osteoporosis, in whom an imbalance in the number of circulating osteoprogenitor cells (OPCs) has been identified. Circulating OPCs form calcified nodules in vitro; however, it remains unknown whether an association exists between the number of circulating OPCs and aortic calcifications. We investigated the relationship between OPCs and aortic calcifications in women with postmenopausal osteoporosis.The number of circulating OPCs was quantified by FACS analysis in 50 osteoporotic postmenopausal women. OPCs were defined as CD15-/alkaline-phosphatase(AP)+ cells coexpressing or not CD34. Participants underwent measurement of markers of bone metabolism, bone mineral density and abdominal aortic calcium (AAC) by 64-slice computed tomography. Patients with AAC were older, had lower 25(OH)vitamin D levels and higher circulating CD15-/AP+/CD34- cells than those without AAC. Significant correlates of AAC included age (rho = 0.38 p = 0.006), calcium (rho = 0.35 p = 0.01), 25(OH)vitamin D (rho = -0.31, p = 0.03) and the number of CD15-/AP+/CD34- cells (rho = 0.55 p 0.001). In regression analyses, the log-transformed number of CD15-/AP+/CD34- cells was associated with the presence (OR = 6.45, 95% CI 1.03-40.1, p = 0.04) and severity (β = 0.43, p 0.001) of AAC, independent of age, 25(OH)vitamin D, calcium and other potential confounders. Patients with low 25(OH)vitamin D and high CD15-/AP+/CD34- cells had higher median AAC than other patients (1927/μL, 862-2714/μL vs 147/μL, 0-1665/μL, p = 0.003).In women with postmenopausal osteoporosis, the number of circulating CD15-/AP+/CD34- cells is significantly associated with increased aortic calcifications, that appear to be correlated also with reduced 25(OH)vitamin D levels.

Nonasthmatic eosinophilic bronchitis (NAEB) is a condition characterized by corticosteroid-responsive chronic cough, sputum eosinophilia and absence of symptoms or objective evidence of variable airflow obstruction and airway hyper-responsiveness. Like asthma, NAEB can be associated with exposure to occupational sensitizers and can be considered as being a variant of occupational asthma when it develops as a consequence of work exposure. Few case reports of NAEB caused by workplace exposure have been reported. Bakers are at high risk of developing occupational respiratory disorders and three cases of occupational NAEB have been described. We describe the first case of occupational NAEB due to storage mites in a baker in which the offending agent was identified by means of the basophil activation test (BAT), a new tool which has never been proposed in diagnostic procedures of occupational respiratory allergy. BAT's results allowed the recognition of the offending agent, that is mandatory for diagnosis.

Deep venous thrombosis (DVT) of the axillary and subclavian veins accounts for approximately 1-2 percent of all recorded deep venous thrombosis. Pulmonary embolism from an upper extremity DVT has been reported to vary between 2 percent and 35.7 percent. We report the occurrence of a left subclavian vein DVT with subsequent nonfatal pulmonary embolism in a sixty-two-year-old patient twenty-four hours following suprapubic prostatectomy. A review of the literature is presented, along with pathophysiology, diagnosis, and treatment.

We have generated a panel of 55 somatic cell hybrids retaining fragments of human chromosome 4. Each hybrid has been characterized cytogenetically by FISH and molecularly by 37 STSs, evenly spaced along the chromosome. The panel can be exploited to map subregionally DNA sequences on chromosome 4 and to generate partial chromosome paints useful in the characterization of chromosomal rearrangements involving this chromosome. Furthermore, a panel of 84 YACs mapping on chromosome 4 has been characterized by FISH. A subset of this panel is recognized by STSs used in the somatic cell hybrid characterization. In this way a correlation between the genetic and the physical maps can be established. These resources have been used to investigate the conservation of the phylogenetic chromosome IV in great apes. The results indicate that all the pericentric inversions that differentiate chromosome IV in these species are distinct and that one of the breakpoints frequently lies very close to the centromere. In 4 instances, the YAC containing the breakpoint was identified. The breakpoint in IVq of PTR and MMU lies in the same YAC, suggesting that this breakpoint has been utilized twice in the evolutionary history of this chromosome.

PURPOSE. Fistula-in-ano anatomy and its relationship with anal sphincters are important factors influencing the results of surgical management. Preoperative definition of fistulous track(s) and the internal opening play a primary role in minimizing iatrogenic damage to the sphincters and recurrence of the fistula. METHODS. Physical examination and endoanal ultrasound (performed with a 10 MHz endoprobe), either conventionally or with an injection of hydrogen peroxide, were performed in 26 consecutive patients. Results were matched with surgical features to establish their accuracy in preoperative fistula-in-ano assessment. RESULTS. Accuracy rates of clinical examination endoanal ultrasound, and hydrogen peroxide-enhanced ultrasound were 65.4, 50, and 76.9 percent for primary tracks, 73.1, 65.4, and 88.5 percent for secondary tracks, and 80.8, 80.8, and 92.3 percent for horseshoe extensions, respectively. Compared with physical examination and endoanal ultrasound, accuracy of hydrogen peroxide-enhanced ultrasound was higher for transsphincteric and intersphincteric primary tracks and horseshoe extensions. Both endoanal ultrasound and hydrogen peroxide-enhanced ultrasound displayed a significantly higher accuracy in detecting the internal openings (53.8 and 53.8 percent, respectively) compared with clinical evaluation (23.1 percent;P=0.027). CONCLUSIONS. Our data suggest that hydrogen peroxide-enhanced ultrasound can be very reliable and useful in the definition of fistula anatomy, its relationship with anal sphincters, and, hence, surgical strategy. It also improves identification of secondary extensions, particularly horseshoe tracks. This method, besides being safe, economic and reputable, both preoperatively and postoperatively, could be helpful in checking operative results and recurrence.

Studies of large numbers of patients have enabled the identification of relatively infrequent chromosome changes, such as inv(3)(q21;q26), t(6;9)(p23;q34) and t(8;16)(p11;p11), whose clinico-biological significance is gradually becoming clearer. Translocations involving chromosomes 1 and 7 are relatively rare in myeloid neoplasias, being found in far less than 1% of cases; the rearrangement that occurs most frequently consists of an unbalanced translocation [t(1;7)(p11; p11)], resulting in complete loss of 7q, associated with therapy-related or environmentally-induced high-risk myelodysplasia. We recently observed three cases of acute myeloid leukaemia (AML) with a previously unreported balanced translocation t(1;7) (p36;q34). Case 1 underwent autologous bone marrow transplantation and remains alive in CR; cases 2 and 3 relapsed after 10 and 4 months, respectively. The response to chemotherapy observed in our cases suggests that variable clinical features might be present in the broad cytogenetic category usually referred to as ‘7q abnormalities’ and contributes to an interesting previous observation of prolonged disease-free survival in a subset of AMLs with 7q− as the isolated chromosome change.

Autoimmune events, although rarely reported during interferon beta-1b (IFNB) treatment of relapsing-remitting (RR) multiple sclerosis (MS), may be more frequent than expected due to the many immunologic abnormalities associated with this disease. We report the prospective two-year follow-up of autoimmune events in 40 RR MS patients treated with IFNB and in 21 untreated MS controls. Thyroid and liver function and serum level of 12 autoantibodies (autoAbs) against organ- (thyroid, gastric, pancreatic) and non-organ-specific antigens were serially monitored. In contrast to control patients, autoAbs (anti-nuclear, -smooth muscle or -thyroid antigens) were detected in 13 IFNB-treated patients, and these were associated with thyroid or liver function alteration in many cases. Persistent autoimmune thyroid dysfunction occurred in three IFNB-treated patients, all of whom were women with a familial history of thyroid disease or baseline anti-thyroid autoAb positivity. For improvement of the MS relapse rate, thyroid dysfunction was adequately treated without stopping IFNB. Liver function alteration (17 IFNB-treated patients, associated with non-organ-specific autoAbs in four) was transient and did not require IFNB treatment to be stopped, with the exception of one patient who was already suffering from a drug-induced hepatopathy at baseline. During the IFNB treatment of MS, several autoimmune events may occur, indicating that thyroid and liver function and autoAbs must be carefully monitored.

In the Canada-USA (CANUSA) Study, the dialysis dose was neither randomized nor held constant, was measured at 6 month intervals, and the relative risk of mortality (R) was found to correlate linearly to mean values of weekly peritoneal plus renal urea clearance normalized to volume, (KprT/ V)m, ranging from 1.5 to 2.3. A risk/dose (R/D) function was derived for continuous ambulatory peritoneal dialysis from kinetic criteria for dose equivalency in hemodialysis (HD) and peritoneal dialysis (PD) and the HD R/D function. This PD R/D function was nonlinear with breakpoint from steep to shallow slope at (KprT/V)ud = 2.00, where ud refers to uniform single doses in contrast to mean doses with wide variances on the mean. The predicted decrease in renal urea clearance KrT/V per 6 months of CANUSA follow-up was computed from serial measured KrT/V in the Randomized Dialysis Prescription and Clinical Outcomes Study and showed it to be 0.21 +/- 0.34. The CANUSA (KprT/V)m values were corrected for the distributed values of 3 months decrements in KrT/V, and the population mortality risk at each (KprT/V)m dose level reported in CANUSA was computed from summation of the product of the R/D curve and fractional distribution of (KprT/V)ud values. From these calculations, the authors conclude that maximum (KprT/V)ud level achieved in CANUSA was 2.00, and the study does not define R/D response above this level.

We have studied three members of a family (mother and two siblings) where the mother and father were first cousins and who presented a history of progressive mental deterioration, hyperkinetic extrapyramidal disorders, and epileptic seizures. They underwent the following examina- tions: cupremia, cupruria, and level of ceruloplasmin, genetic analysis for SCA1, 2, 3, 6, dentato-rubric-pallido-luysian atro- phy, and Huntington's disease, electromyography (EMG), electroencephalography (EEG), brain magnetic resonance imaging (MRI), and investigation of acanthocytes with scan- ning electron microscopy. Genetic analysis was negative in all patients and acanthocytes were positive. EMG showed an axonal neuropathy in one sibling, EEG showed epileptiform activity in the two siblings, and MRI showed cortical atrophy in all subjects. This family shows the great variability of neu- roacanthocytosis and a dominant autosomal transmission, as described only once previously in the literature. Results Neurological examination showed tics, oro-facial dyskine- sia, and dystonia of the limbs in all subjects; neuropsycho- logical valutation showed a mild mental deterioration in all subjects. Cupremia, cupruria, level of ceruloplasmin, and all the genetic analyses were negative in all subjects. EMG showed a motor-sensitive axonal neuropathy in the female sibling. EEG showed bitemporal epileptiform activity in the two siblings, but not in the mother. MRI scans showed a hypointensity of the white matter in the T1-weighted images and a hyperintensity in the T2-weighted images, without enhance- ment with gadolinium in the parietal lobe of the male sibling. Global cerebral atrophy was observed in all subjects. Scanning electron microscopy revealed acanthocytes in all subjects. The siblings have been given antiepileptic therapy and neu- roleptics, with a good control of epileptic seizures and suffi- cient control of involuntary movements at the beginning of treatment. However, there has been progression in the last year.

The identification of prognostic factors which influence the long-term results of dental retransplantation and autotransplantation is one of the main aims of clinical research whose principal scope is remove or alter those factors which have a negative influence on outcome, and to identify the causes of failure and areas for improvement. The paper reports the most significant results of a clinical survey which was carried out on 135 patients who had undergone retransplantation and/or autotransplantation and were then followed for 8 years.

The University of Southern California School of Medicine conducted a nationwide survey of 336 nephrologists to obtain demographic and clinical data on 6,411 patients with end-stage renal disease (ESRD). Patient demographic data, along with ESRD etiology and comorbid conditions noted by the physician, were compared across various modalities of dialysis. Characteristics of the treatment provided were differentiated by the mode of dialysis and the location of the patient encounter. Results of the analysis show that patients on peritoneal dialysis are more likely to be female and have higher rates of diabetes compared with hemodialysis (HD) patients. Statistically, patients on intermittent peritoneal dialysis are older, more likely to be black, and have a higher incidence of cardiovascular conditions. Continuous ambulatory peritoneal dialysis patients have greatest problem severity and require more physician time and more complex services, whereas home HD patients require the greatest number of diagnostic tests and therapeutic procedures. Hospital inpatient care shows greater case-mix severity and more intensive treatment, but this does not differ by the mode of dialysis. Finally, patients of freestanding dialysis facilities are more likely to have hypertensive renal disease, whereas patients at hospital-based facilities are older, more likely to be seen in the hospital, have more urgent and severe problems during dialysis rounds, and require more physician time, more complex services, and more diagnostic tests and therapeutic procedures.

An immunogold postembedding method for the ultrastructural localization of immunoglobulin G (lgG), IgA, IgM, C3, fibrinogen, and kappa and lambda immunoglobulin light chains was established. The method was performed on surplus tissue from renal biopsies fixed in 2% glutaraldehyde and embedded in acrylic LR White resin. Fifteen cases were studied and the localization of antigen in the dense deposits in glomeruli compared with the immunofluorescence (IF) findings on the same cases. The results obtained by IF and immunoelectron microscopy (IEM) were comparable for IgG and IgA. In most instances, IgM and C3 were more intensely labeled by IF than IEM. Some discrepancies were noted for fibrinogen. It is postulated that these differences are related to a partial loss of antigenicity due to fixation or chemical reaction with the embedding medium. The advantage of IEM resides in localizing antigens in very small deposits seen in early stages of glomerulonephritis. The method can supplement IF in diagnostically difficult cases or be substituted for it when material for IF is not available.

The endodontic endosseous implants were used to a lot of clinic indication. The Authors suggest their use in the median fractures of roots and describe the operative technic, of which they consider the long-term results.

From 53 cases of thrombosis of the internal carotid artery in the neck, collateral circulation through external carotid branches was angiographically demonstrated in 34 subjects. Anastomosis between external and intracranial circulations was seen to take place through three ways formed by internal maxillary, superficial temporal and facial arteries. The role of internal maxillary artery is emphasised as the most important pathway in the connections between the two circles.

The Network Coordinating Council (NCC) #4 continuous ambulatory peritoneal dialysis (CAPD) study was designed to gather basic demographic information and analyze selected outcome parameters on all patients started on CAPD in Southern California/Southern Nevada. Between early 1979 and Dec 31, 1983, 775 patients were enrolled in the study for a total experience of 878.5 patient-years. Demographic data revealed 25% of patients were over 60 years old and 17.4% were less than 20 years old at the start of CAPD, 65% were white, and 28% had chronic glomerulonephritis as a cause of end-stage renal disease (ESRD). Compared to all NCC #4 patients on dialysis (hemo and peritoneal), the young (less than 20 years old) and whites were overrepresented on CAPD. Patient outcome was assessed by life table analysis which revealed 90%, 80%, 70%, and 70% patient survival at 12, 24, 36, and 43 months, respectively; and technique success of 80%, 60%, 48%, and 40% for the same time periods, respectively. Over half of the dropout from CAPD and one third of the hospitalizations were related to recurrent infection. Few patients transferred from CAPD because of dissatisfaction with the technique or because of peritoneal membrane failure. CAPD is an excellent form of therapy for ESRD that controls uremia adequately and improves the quality of life for many patients. Long-term application of CAPD is hampered, however, by the high frequency of recurrent infections.

The authors relate about 3 cases of newborn babies with adrenal haemorrhage. The only clinical sign found was the palpation of the lowered kidney. The diagnosis was made after an abdominal ultrasonography which turned out to be the decisive instrumental analysis.

After an analysis of the prosthetic troubles about atrophic edentulous ridges, the Authors describes the lowering mental nerve operation and consider its therapeutic benefit.

OBJECTIVE:\ud We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy.\ud \ud METHODS:\ud A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered.\ud \ud RESULTS:\ud The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively.\ud \ud CONCLUSIONS:\ud This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV.

Introduction: Self-inflicted orchidectomy and auto-castration, also known as “Eshmun complex” is a rare phenomenon. The aim of our study it to present the management of a patient who performed a self orchiectomy and propose a non-systematic review of literature about self-orchiectomy. Material and method: A 27-years old male Patient with psychiatric disorder was admitted to our ward to have been cutted his scrotum with scissors and cut away his left testicle causing active bleeding from the left spermatic artery. The patient underwent emergency surgery with clamping of the spermatic cord and hemostasis of the wound. Results: After surgery the clinical condition of the patient remained good during whole hospitalization. Urgent psychiatric evaluation was performed in order to administer proper therapy for acute management. To best of our knowledge, only 11 cases of self-orchidectomy are reported in literature and all of them except 1 case, underwent surgical exploration. Conclusions: Self-orchidectomy is an extremely rare phenomenon, often associated with psychiatric disorders, compounded by the use of drugs. In our opinion, emergency surgery should be the first choice of treatment, offering diagnostic and hemostatic purpose in a single act, aimed to prevent acute and postacute complications.