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Introduction: Osteoporosis is a metabolic skeletal disease characterized by low bone mass and strength, and increased risk for fragility fractures. It is a major health issue in aging populations, due to fracture-associated increased disability and mortality. Antiresorptive treatments are first line choices in most of the cases., Areas Covered: Bone homeostasis is complicated, and multiple factors can compromise skeletal health. Bone turnover is a continuous process regulated by the coupled activities of bone cells that preserves skeletal strength and integrity. Imbalance between bone resorption and formation leads to bone loss and increased susceptibility to fractures. Antiresorptives prevent bone loss and reduce fracture risk, by targeting osteoclastogenesis and osteoclast function and survival. Their major drawback is the coupling of osteoclast and osteoblast activity, due to which any reduction in bone resorption is followed by suppression of bone formation., Expert Opinion: During the last couple of decades significant progress has been made in understanding of the genetic and molecular basis of osteoporosis. Critical pathways and key molecules that mediate regulation of bone resorption have been identified. These factors may underpin novel therapeutic avenues for osteoporosis, but their potential for translation into clinical applications is yet to be tested.

Introduction: Invasive fungal diseases (IFD) constitute a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients., Areas Covered: We describe epidemiology, causes and risk factors of IFD in allogeneic HSCT discussing prophylaxis and treatment in various HSCT phases. We present the most recent studies on this thematic area, including novel data on currently available antifungals, i.e. formulations, dosing, safety, efficacy and therapeutic drug monitoring. Finally, we present the most recent relevant recommendations published. Literature search included PubMed, Scopus, and clinicaltrials.gov between January 2014 and April 2024., Expert Opinion: The antifungal agents employed for prophylaxis and therapy should be predicated on local epidemiology of IFD. Fluconazole prophylaxis remains a first-line choice before engraftment when the main pathogen is Candida spp. After engraftment, prophylaxis should be with mold-active agents (i.e. triazoles). For candidiasis, echinocandins are suggested as first-line treatment, whereas aspergillosis responds well to mold-active azoles and liposomal amphotericin B (L-AmB). For mucormycosis, treatment of choice includes L-AmB and isavuconazole. Choice between fever-driven and diagnostics-driven strategies remains equivocal. Open research topics remain: 1) optimization of tools to ensure prompt and accurate IFD diagnosis to avoid unnecessary exposure to antifungals, drug interactions and cost; 2) refinement of treatment for resistant/refractory strains.

Nesfatin concentrations are positively correlated with beta cell function. However, it is unclear whether diet composition mediates this relationship. We recruited 27 overweight individuals who practiced Orthodox fasting (OF), a subset of the Mediterranean diet (MedDiet), for 7 weeks. Fourteen overweight people who practiced 16:8 time-restricted eating served as control group. Anthropometric parameters, biochemical data and adipokine levels were evaluated at baseline and after the end of the diet period (7 weeks from baseline). Subsequently, participants were asked to return to their usual eating plans, and an additional evaluation was performed 5 weeks after the end of the research diets (12 weeks from baseline). We observed a significant and negative correlation between HOMA-B and nesfatin values at 12 weeks, only in the OF group ( r = -0.455, p  = 0.01). In conclusion, returning to normal eating habits after 7 weeks of strict adherence to MedDiet affects the homeostatic balance between insulin secretion and nesfatin.

Background: This study aimed to investigate the association between clinical and laboratory parameters and response to therapy with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes mellitus (T2D)., Research Design and Methods: We retrospectively analyzed the medical records of people with T2D in whom SGLT2i was started. Clinical and laboratory parameters were recorded before, 3 and 6 months after starting treatment. Specific criteria were applied to classify participants into good and poor responders in terms of weight loss (primary outcome) and glycemic control (secondary outcome), separately., Results: Fifty individuals (64% men) with a mean age of 65.8 ± 8.5 years were included in the analysis. 86% and 64% of the participants were classified into good response categories for glycemic control and weight loss, respectively. Good responders in terms of glycemic control had lower high-density lipoprotein cholesterol levels at baseline compared to poor responders (43.3 vs 57.4 mg/dl, p  = 0.044). In the logistic regression analysis, a higher baseline weight was associated with a better response to therapy in terms of weight loss ( p  = 0.04)., Conclusions: Our findings suggest that specific clinical and laboratory parameters are associated with response to SGLT2i treatment and can contribute to a more personalized approach to T2D care.

Objectives: The factors determining the response to treatment with glucagon-like peptide-1 receptor agonists (GLP-1- RAs) have not been clarified. The present study investigated the association between polymorphisms in TCF7L2 , CTRB1/2 , and GLP-1 R genes and response to GLP-1 RAs regarding glycemic control and weight loss among Greek patients with type 2 diabetes mellitus (T2DM)., Methods: Patients ( n  = 191) treated with GLP-1 RAs for at least 6 months were included. Participants were genotyped for TCF7L2 rs7903146 (C>T), CTRB1/2 rs7202877 (T>G) and GLP-1 R rs367543060 (C>T) polymorphisms. Clinical and laboratory parameters were measured before, 3, and 6 months after treatment initiation. The patients were classified into responders and non-responders according to specific criteria., Results: Carriers of at least one rs7903146 'T' allele and rs7202877 'G' allele presented similar glucose control and weight loss response to GLP-1 RAs with the respective homozygous wild-type genotypes [odds ratio (OR): 1.08, 95% confidence interval (CI): 0.5, 2.31, p  = 0.85 and OR: 1.35, 95% CI: 0.66, 2.76, p  = 0.42; OR: 1.4, 95% CI: 0.56, 3.47, p  = 0.47 and OR: 1.28, 95% CI: 0.55, 2.98, p  = 0.57, respectively]. Regarding the GLP-1 R polymorphism, all participants were homozygous for the wild-type allele; thus, no comparisons were feasible. Female sex ( p  = 0.03) and lower baseline weight ( p  = 0.024) were associated with an improved glycemic and weight loss response, respectively., Conclusion: There is no evidence suggesting a role for the variants studied in response to GLP-1 RA therapy in people with T2DM. However, specific demographic and clinical factors may be related to a better response to treatment with these agents.

Background: The role of high sensitive cardiac Troponin (hs-cTn) in patients with liver cirrhosis (LC) and liver-related acute events is not well established., Aim: To assess the prognostic performance of hs-cTn I in acute decompensation (AD) and acute-on-chronic liver failure (ACLF)., Methods: Two cohorts of consecutive patients, a derivation (retrospective) and a validation (prospective), were evaluated and 30-day-mortality was recorded. Hs-cTnI values were measured. Very low hs-cTnΙ (4 ng/L) was considered the cutoff-level., Results: A total of 296 patients with LC [69.3% male, median age 57 (IQR 51-68) years, MELD score 19 (13-25), ACLF (29.4%), AD (48.3%), and without liver-related acute events (22.3%)] were included in the derivation cohort. The 66.2% of total patients had hs-cTnI ≥4 ng/L. Patients with hs-cTnI ≥4 ng/L were older and had more severe LC compared to those with <4ng/L. The multivariate analysis demonstrated that age ( p  < 0.001) and MELD ( p  = 0.001) were independent variables associated with elevated hs-cTnI after adjustment for age, sex and hepatic encephalopathy in total patients.When ACLF and AD were analyzed separately, the mortality was higher in patients with hs-cTnI ≥ 4 ng/L compared to lower values (log-rank p  = 0.036 and p  = 0.019, respectively). In multivariate analysis, MELD ( p  < 0.001) and hs-cTnI ≥4 ng/L ( p  = 0.032) were independent prognostic factors of mortality in ACLF/AD groups, after adjustment for age and sex. Similar results were obtained from the validation cohort ( N  = 148)., Conclusions: hs-cTnI levels were higher in patients with severe liver disease. The low cutoff-point of 4 ng/L is accurate in ruling out non-survivors mainly in AD group.

Purpose: Adolescent pregnancy, while recently in decline, remains a matter in need of addressing. Education and counselling are deemed crucial and this review aims at comparing published contraceptive guidelines, thus resolving any surrounding misconceptions., Materials and Methods: Recently published contraception guidelines regarding adolescent pregnancy were retrieved. In particular, guidelines and recommendations from ACOG, RCOG, SOCG, AAP, CPS, NICE, CDC, and WHO were compared and reviewed based on each guideline's method of reporting., Results: Three categories of contraceptive methods are available for adolescents and recommendations on their initiation should be made based on their efficacy, according to all guidelines. Therefore, long acting reversible contraceptives (LARCs) should be highly recommended as the most effective method (typical use failure rate: 0.05%), followed by short-acting hormonal contraceptives (typical use failure rate: 3-9%). The third contraceptive option includes contraceptives used in the moment of intercourse and displays the lowest effectiveness (typical use failure rate: 12-25%), mostly due to its dependence on personal consistency, however offers protection against STI transmission., Conclusion: Adolescents should be encouraged to initiate contraception, with LARCs being the primary choice followed by short-acting hormonal contraception. However, regardless of the chosen effective contraceptive method, the use of condom is necessary for STI prevention.

Purpose: The authors discuss the need for newborn screening in the context of the migration policy of the European Union, and particularly, the European Asylum, Migration and Integration Fund., Methods: The authors searched scholarly databases (Pubmed, Scopus, Google scholar) and grey literature (LexEuropa, Policy reports) to identify original peer-reviewed research examining the migration to the European Union and the provision of healthcare to infants born to refugees and immigrant mothers. Resources in language different from English, French, German and Greek were not taken into consideration., Results: Every year, a large number of refugees and immigrants from sub-Saharan Africa and Middle East countries travel to and enter in Europe. It has been estimated that two thirds of those seeking asylum are women and children. Many of these children have been born on the way to Europe or in migrant camps. Essential newborns' health screening is not accessible in most cases. Congenital conditions such as hypothyroidism and phenylketonuria may remain untreated, and once these infants are diagnosed, the organic damage could be irreversible. Prolonged necessary hospitalisation might be out of consideration at a time when clinics and hospitals are overstrained with COVID-19 patients., Conclusions: It is essential to ensure that newborn screening will be performed in a timely and evidence-based manner as well as that the information will be communicated between hospitals and within countries' health networks. In order to achieve these goals interdisciplinary and international technical and logistical collaboration are required.

Background: Several safe and effective vaccines against nCoV-19 have been developed to contain the pandemic with very few severe adverse-reactions reported. Vaccine-induced interstitial lung disease (ILD) is a very rare and difficult to recognise and diagnose adverse-reaction and is mostly associated with Influenza vaccines., Methods: We report a 55-yr old male who presented with severe respiratory failure that required for several days oxygen supplementation with high flow nasal cannula, and myocardial infarction. Symptoms onset was eighteen days after the first shot of adenoviral AZD1222 vector vaccine. Possible SARS-CoV-2 natural infection post-vaccination was excluded with rigorous laboratory work-up including multiple nasopharengeal rt-qPCR tests for SARS-CoV-2 detection and close monitoring of his serum SARS-CoV-2 antibodies. Other potential infectious agents and alternate diagnoses were thoroughly investigated., Results: Patient responded impressively to high dose steroids. A repeat chest CT nine days after the first one showed a remarkable resolution of the bilateral ground glass opacities. Except for his cardiology medication, no supplemental oxygen neither steroids were prescribed upon his discharge. On one month follow-up, no residual pulmonary dysfunction was noticed with patient preserving a SatO2 of 97-98% on ambient air., Conclusion: Vaccine-induced ILD might constitute a rare nCoV-19 post-vaccination adverse-event. According to current restricted data, when post-vaccination ILD is early suspected and recognised, then prompt implementation of steroid treatment reverses significantly the lung lesions without progression to fibrosis.

Introduction: According to their selectivity for sodium-glucose cotransporters (SGLT) 1 and 2, gliflozins could be subdivided into two additional categories: pure SGLT2 inhibitors, which are highly selective for SGLT2, and dual SGLT1/2 inhibitors which, in addition to SGLT2, exhibit strong inhibitory activity for SGLT1., Areas Covered: This article aims to discuss whether the pharmacological differences between the two subtypes of gliflozins could be translated into different efficacy and safety characteristics that might be important for clinical practice., Expert Opinion: In large cardiovascular outcome trials, dual inhibitors have shown a unique efficacy profile in terms of reducing glycemia in patients with severe renal impairment and decreasing the risk of atherosclerotic outcomes. These features do not characterize selective SGLT2 inhibitors and could be attributed to the parallel inhibition of SGLT1. The increased risk of diarrhea and severe hypoglycemia observed only with dual inhibitors is probably related to their action in the gut and brain, respectively. However, differences in populations included in various studies should be considered when attempting to translate their findings into clinical practice; therefore, head-to-head trials are needed to shed more light on this issue and provide clear guidance to clinicians.

Red blood cell (RBC) transfusions have been established as one of the primary therapies in treating sickle cell anemia. However, they are not free of side effects, with overloading the body with iron being one of the most important. Iron chelation therapy greatly reduces the iron load of the body. In addition, hydroxyurea (HU), an oral chemotherapeutic drug also has a significant role in the treatment of the disease with beneficial effects on many of the clinical problems that arise, mainly in reducing painful crises. The aim of this study was to investigate the effect of synergistic transfusion therapy and HU on the response to deferasirox (DFX) chelation therapy. Eighteen patients with sickle cell disease were divided into two groups based on their treatment, either with simple transfusions and DFX or with a combination of transfusion therapy, DFX and HU, and were evaluated with magnetic resonance imaging (MRI) for liver iron concentration (LIC) and biochemistry. All patients completed the study. The results of the study showed improvement in serum ferritin (FER) levels and LIC after 12 months of therapy in both groups, especially in the group receiving the combination therapy with HU. In addition, there was a noteworthy improvement in serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and lactate dehydrogenase (LDH) levels with serum creatinine (Cr) levels remaining stable during the study in both groups. Hydroxyurea, when combined with iron chelators such as DFX, provides an additional benefit of iron chelation in patients receiving chronic transfusion therapy.

Introduction: Invasive fungal diseases (IFDs) are a significant cause of morbidity and mortality among immunocompromised patients. Safe and effective antifungal medications used for prophylaxis and treatment are pivotal in their management. Posaconazole is a promising triazole antifungal agent., Areas Covered: The authors discuss the pharmacological properties of posaconazole, including pharmacokinetics/pharmacodynamics, safety and tolerability profile, together with efficacy data for prophylaxis and treatment as well as its use in special populations based on current literature., Expert Opinion: Posaconazole has a favorable safety and tolerability profile; however, caution is advised when co-administered with agents that are CYP3A4 inhibitors, because their concentration may significantly increase, and their levels should be closely monitored. It has an extended spectrum of activity against yeasts and filamentous fungi. It is successfully used as prophylaxis for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and post-hematopoietic cell transplantation (HCT) with graft-versus-host disease (GVHD). It is the first line treatment for oropharyngeal candidiasis and is also used as a salvage treatment for refractory IFDs. Currently available formulations include the oral suspension, delayed-release tablets and solution for intravenous infusion, all with different PK/PD properties and indications. Its use in children and adolescents is currently being examined in Phase-II clinical trials.

Objective: Simulated endoscopic training can be challenging and stressful for the novice trainee. The absence of a reliable stress detection method during simulated endoscopic training makes estimating trainees' mental stress difficult to quantify. This study concomitantly measures the responses of four saliva stress biomarkers and compares them to the video score (VS) achieved by novice endoscopists in a reproducibly stressful simulation environment., Methods: Thirty-six male endoscopy naïve surgery residents were enrolled. After an orientation phase, a saliva specimen was collected for cortisol (sC), alpha-amylase (sAA), Chromogranin A (sCgA), and immunoglobulin A (sIgA) measurements (baseline phase, BL). Thereafter, the simulation exercise phase (E) started, practicing in the Fundamentals of Endoscopic Surgery Skills module (GI-Bronch Mentor). Immediately after, a second saliva sample for measuring the above-cited biomarkers was collected. The whole experiment was videotaped, and the VS was calculated. The percentage (E-BL) diff of each of the four saliva biomarkers was calculated and examined for correlation to VS., Results: sCgA diff showed the best correlation with VS, followed by sAA diff ., Conclusions: sCgA and sAA, are saliva stress biomarkers that are easy to collect non-invasively and showed the best correlation with novice endoscopist's performance in our simulation setting, and therefore, they could be used for monitoring stress.

OBJECTIVE : Early identification of neonates at risk of neurological impairment is particularly important for the bedside clinician. Clinical value of S100b and neuron-specific enolase in neonates has not been yet established. We investigated their kinetics and possible early clinical utility in neonatal encephalopathy (NE). STUDY DESIGN : 36 full-term neonates (13 with moderate/severe encephalopathy, 11 with mild encephalopathy, 12 controls) were enrolled and studied prospectively. Serum S100b and neuron-specific enolase (NSE) were measured serially on days(d) 1, 3, 9 and 18 of life. Brain MRI and long-term neurodevelopmental outcome were also assessed. RESULT : Neonates with moderate/severe encephalopathy had significantly increased S100b (d1) and NSE levels (d1, d3, d9) compared to controls. Neuron-specific enolase significantly correlated with the degree of encephalopathy, and a cutoff of 38.8 μg/l (d1) accurately predicted moderate/severe encephalopathy. S100b (d1) cutoff points of 1.6 μg/l and 11.4 μg/l prognosticated severe encephalopathy and death/cerebral palsy, respectively. Both biomarkers correlated well with neuroimaging and Bayley-III scores. CONCLUSION : Combined clinical, laboratory, imaging and neurodevelopmental data indicate that serum S100b and NSE can be useful biomarkers for the diagnosis and prognosis of neonatal brain injury, providing useful information to the bedside clinician.

Purpose: To describe the presence of outer retinal tubulations (ORTs) in a patient diagnosed with maternally inherited diabetes and deafness (MIDD) - associated macular dystrophy., Methods: The patient underwent clinical examination assessing best-corrected visual acuity (BCVA), anterior segment evaluation and fundoscopy followed by optical coherence tomography (OCT). Audiological evaluation was also performed for the accurate diagnosis of MIDD., Results: A 57-year-old diabetic patient with mildly affected BCVA, macular dystrophy and severe neurosensory hearing loss was diagnosed with MIDD. Examination with OCT revealed the central loss of photoreceptors and the presence of ORTs in close proximity to the fovea. Regular follow-up seven months after her initial visit showed no alterations in the clinical and imaging status of the patient. In the context of family screening, the patient's sister presented with the diagnosis of pre-diabetes and a moderate sensorineural hearing loss, while fundus examination and OCT revealed no significant pathology. In this report, we present ORTs in association with MIDD., Conclusions: ORTs are a non-specific finding that can be found in MIDD and other retinal dystrophies. Taking under consideration the rarity and the difficulty in diagnosing this entity, our data could serve as an addition to the existing knowledge in terms of clinical and imaging manifestations of MIDD.

Background: The complement system has been recently proposed to play an important role in the pathogenesis of ANCA-associated vasculitis (AAV). This study evaluated the value of serum and kidney deposited C3 in predicting renal outcomes in AAV., Methods: This was a retrospective study of 47 patients with AAV, who were categorized according to their serum C3 levels as hypo- or normo-complementemic and to those with positive or negative kidney biopsy immunofluorescence (IF) for C3. Baseline characteristics as well as progression to end-stage renal disease (ESRD) between the 2 groups were compared., Results: In total, 23% (11/47) were hypo-complementemic; these patients were older (74 vs. 65 years, p  = 0.013), had higher creatinine levels (4.9 vs. 2.2 mg/dL, p  = 0.006), were more often hemodialysis dependent (64% vs. 19%, p  = 0.009) and progressed more often to ESRD (55% vs. 11%, p  = 0.01) compared to normo-complementemic patients ( n  = 36). On multivariate analysis, serum creatinine at diagnosis (HR = 16.8, 95%CI: 1.354-208.62, p  = 0.028) and low serum C3 (HR = 2.492; 95% CI: 1.537-11.567; p  = 0.044) were independent predictors for ESRD. Among 25 patients with an available kidney biopsy, 56% had C3 deposition by IF and displayed more often a mixed histological pattern (72% vs. 27%, p  = 0.033), low serum C3 levels (42% vs. 18%, p  < 0.001) and serious infections during follow-up (57% vs. 18%, p  = 0.047) compared to those with negative ( n  = 11) IF staining., Conclusion: Almost one of four patients with AAV has low C3 levels at diagnosis which is associated with more severe renal disease and worse renal outcomes (ESRD). This should be taken into account in therapeutic and monitoring strategies.

Hemoglobinopathies exhibit a remarkable phenotypic diversity in terms of disease severity, while individual genetic background plays a key role in differential response to drug treatment. In the last decade, genomic variants in genes located within, as well as outside the human β-globin cluster have been shown to be significantly associated with Hb F increase, in relation to hydroxyurea (HU) therapy in patients with these diseases. Here, we aim to determine the effect of genomic variants located in genes, such as MAP3K5 , ASS1 , NOS2A , TOX , PDE7B , NOS1, FLT1 and ARG2 , previously shown to modulate fetal hemoglobin (Hb F) levels in patients with β type hemoglobinopathies and reflecting disease severity and response to HU therapy in an independent cohort of Greek patients with these diseases. We recruited and genotyped 45 β-thalassemia patients (β-thal), either transfusion-dependent (TDT) or non transfusion-dependent (NTDT), 42 Hb S ( HBB : c.20A>T)-β-thal compound heterozygotes, who were treated with HU, as well as 53 healthy individuals, all of Hellenic origin. Our study showed that genomic variants of the MAP3K5 , NOS2A and ARG2 gene are associated with HU therapy efficacy in Hb S-β-thal compound heterozygotes. We have also shown that FLT1 and ARG2 genomic variants are associated with the mild phenotype of NTDT patients. Our findings provide evidence that MAP3K5 , NOS2A , ARG2 and FLT1 genomic variants could be considered as genomic biomarkers to predict HU therapy efficacy in Hb S-β-thal compound heterozygotes and also to describe disease severity in patients with β type hemoglobinopathies.

Herbal supplements are widely used during pregnancy, although there are insufficient data regarding their efficacy and safety. Some of them have been associated with hypertension, including licorice, which induces the so called mineralocorticoid-excess syndrome, a clinical picture resembling to pseudohyperaldosteronism. This action is mediated via inhibition of 11-hydroxysteroid dehydrogenase type 2 (11-HSD2), leading to impaired inactivation of cortisol to cortisone, accumulation of cortisol, and finally to excessive mineralocorticoid activity, especially in the distal and cumulative tubule of kidneys. This syndrome is characterized by hypertension and hypokalemia. Herein, we report a case of a 37-year-old pregnant woman, who was referred from obstetrics department to our department due to persistent hypertension and hypokalemia. She consumed a herbal supplement called "mumijo" during the last 6 months. After a thorough diagnostic work-up, the diagnosis of a "licorice-like syndrome" due to mumijo consumption was made. Potassium supplementation at the acute phase and discontinuation of mumijo were the treatment of choice. This is the first report of pseudohyperaldosteronism due to mumijo consumption in literature. Clinicians should be aware of this side effect and this agent should be included in those causing pseudohyperaldosteronism. Besides all, our case highlights the undeniable value of a detailed medical history.

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication in patients with sickle cell disease, characterized by difficulties in diagnosis and management. Certain reports have suggested successful salvage treatment with the terminal complement inhibitor, eculizumab. We here report evidence of complement activation and successful complement inhibition with one dose of eculizumab in an adult sickle cell disease patient presenting DHTR with hyperhemolysis. A 21-year old female sickle cell disease patient [Hb S (HBB: c.20A>T)/β-thalassemia (β-thal)] presented at our Adult Thalassaemia Unit, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece, with headaches, perioral numbness and pain in both antibrachia. The patient was admitted with the diagnosis of vaso-occlussive crisis (VOC) and treated symptomatically. On her third day of admission, due to hemoglobin (Hb) value of 6.9 g/dL with increase in reticulocytes, the patient was transfused with one unit of compatible leukodepleted red blood cells (RBC). The following day, hemolytic parameters increased, although Coombs, panel antibodies and screening tests were negative. Five days later, she again received a unit of RBCs, resulting in another increase of hemolytic parameters. During the following 2 days, there was a dramatic decrease of Hb levels to 5.4 g/dL with reticulocytes at 6.0%, negative Coombs testing and negative alloantibodies. Based on these findings, we recognized the syndrome of DHTR with hyperhemolysis. Given the lack of immediate access to other treatment, we administered intravenous rituximab, immunoglobulins and corticosteroids. As there was no response, one dose of eculizumab (900 mg) was then administered with ciprofloxacin as prophylaxis. The patient remains well 6 months post treatment.

Purpose: The purpose of this study was to investigate the changes that occur in the levator ani muscle (1) during pregnancy and (2) after labor depending on the mode of delivery in a cohort of nulliparas., Materials and Methods: A prospective cohort longitudinal study, consisting of 84 primiparas who were examined and recruited in an antenatal clinic was conducted. All participants were submitted to a real-time three-dimensional (3D) ultrasonographic evaluation of the levator ani at (1) 12, (2) 22, and (3) 32 weeks of pregnancy (4) and 4-6 months postdelivery. The 3D volumes were acquired and stored for an offline analysis., Results: Data from 59 women with at least two measurements were available for analysis. 35 women were delivered vaginally and 24 via cesarean section. There was a statistical increase in the dimensions of the levator hiatus at each pregnancy trimester when compared to the measurements of the previous trimesters. After vaginal delivery, hiatal dimensions increased compared to the third-trimester measurements; after cesarean section, hiatal dimensions decreased., Conclusions: This study supports that in primiparas, the dimensions of the levator hiatus increase significantly during pregnancy and subsequently either increase further after vaginal delivery or decrease to the first-trimester levels after cesarean section.

Objectives: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD., Methods: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter., Results: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p = .974) but a worse, yet adequate, in the ACLF-group at 28 days (p = .08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel's concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh., Conclusions: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.

Objective: The rates of blood pressure (BP) control worldwide are discouraging. This study had the purpose of assessing the effectiveness of perindopril/amlodipine fixed dose combination on BP-lowering efficacy, and recording adherence, safety and tolerability during a 4 month treatment period., Research Design and Methods: In this multicenter, observational study 2269 hypertensive patients were prospectively enrolled. The data were recorded at 1 and 4 months of treatment., Main Outcome Measures and Results: Between the first and third visits mean BP values (systolic/diastolic) decreased from 158.4 ± 13.6/89.9 ± 8.7 mmHg to 130.0 ± 7.9/77.7 ± 6.3 mmHg (P < 0.001). The magnitude of BP reduction depended on baseline blood pressure levels and total cardiovascular (CV) risk (P < 0.001). Patients with grade 1, 2 and 3 showed a BP reduction of 21.9/10.0 mmHg, 34.4/14.2 mmHg and 51.4/21.2 mmHg, accordingly (P < 0.001). Patients with very high, high, moderate and low added CV risk showed a BP reduction of 35.7/14.9 mmHg, 27.5/12.1 mmHg, 28.6/12.2 mmHg and 14.5/5.8 mmHg respectively (P < 0.001). Adherence to treatment was high: 98.3% of the sample was taking the treatment "every day" or "quite often", while only 15 patients (0.7% of the sample) prematurely discontinued treatment. Study interpretation may be limited by the fact that this is an observational study with no comparator and a short follow-up period., Conclusions: A perindopril/amlodipine fixed dose combination significantly decreases BP levels. The degree of BP reduction is related to baseline BP levels and total CV risk.

Purpose To evaluate the in vitro efficacy of several anti-staphylococcal agents against a nationwide collection of contemporary Staphylococcus aureus clinical isolates from several healthcare centres in Greece. Methods Thirty hospitals throughout Greece (18 in Attica) provided all clinical isolates of S.aureus from April 2012 to May 2013 to a central lab to be re-submitted to susceptibility testing. The MICs were evaluated by Vitek® 2 with the exception of ceftaroline (OXOID M.I.C. Evaluator™). Vancomycin and daptomycin MICs were also evaluated by Etest®. Heterogeneously vancomycin-intermediate strains (hVISA) were detected by the Etest® GRD. VISA phenotype was confirmed by PAP-AUC. Results A total of 1005 isolates (39% MRSA) were studied. Susceptibility rates were: erythromycin 66.5%, clindamycin 79.2%, SXT 98.9%, rifampicin 97.3%, fusidic acid 67%, moxifloxacin 78.8%, vancomycin 99.9%, ceftaroline 92.9% and linezolid, tigecycline and daptomycin 100%. For mupirocin, high level resistance could be excluded for 98.9% of isolates. Vancomycin Etest® MIC 50/90 were 1.5/1.5 mg/L, 58.5% of isolates exhibited a MIC > 1 and 8.7% a MIC of 2 mg/L, while Vitek® MIC 50/90 were 1/1 and 3.1% showed MIC > 1 mg/L. One VISA strain was detected. Among the selected 175 isolates that were screened for hVISA phenotype, six (3.4%) were positive. In 315 bloodstream isolates, 64.1% had a vancomycin Etest® MIC > 1 mg/L. Conclusions This multi-centre surveillance study revealed that a significant percentage of contemporary S.aureus isolates from Greek patients have a vancomycin MIC (> 1 mg/L) that may compromise the clinical efficacy of the drug for the treatment of serious infections. The in vitro activity of SXT, rifampicin, mupirocin, linezolid, tigecycline, daptomycin and ceftaroline remains excellent.

Objective: To study pregnancies achieved after liver transplantation in terms of obstetric complications, maternal, neonatal outcomes and post-pregnancy allograft function., Methods: A retrospective study of prospectively collected data was conducted, enrolling women with a history of liver transplantation performed in the Transplantation Unit of our hospital that delivered in our department. Obstetric characteristics and antenatal complications were reviewed. Apgar score, admission to Neonatal Intensive Care Unit (NICU) and need for emergency intubation were analyzed. Outcomes of regular follow-up concerning all complications of allograft function observed after pregnancy were also studied., Results: There were five cases of allograft recipients delivering their pregnancies during the study period. Mean maternal age was 32.2 ± 5 years. Interval from transplantation to delivery ranged from 40 to 219 months. Mean gestational week at delivery was 34.4 ± 2.5 weeks. Antenatal complications observed were pre-eclampsia (3 of 5 cases) and vaginal bleeding (1 of 5 cases). All preterm neonates were admitted to NICU, but no emergency intubation was demanded. One patient died a month after delivery, while three others were complicated by implant dysfunction up to 5 years after the delivery., Conclusion: Pregnancy in a liver transplant recipient is associated with complications for mother and infant.

Objectives: Angiogenesis and inflammation have been involved in the progression of fibrosis in patients with chronic liver disease (CLD). Soluble CD146 (sCD146), a biomarker that was recently characterized as a novel component of the endothelial junction is implicated in endothelial proliferation. Our study evaluates the performance of sCD146 in assessing liver fibrosis and cirrhosis, and determines if its levels are related to the severity of liver disease in patients with cirrhosis., Material and Methods: sCD146 levels were determined by a commercially available immunoenzymatic technique in 62 consecutive patients with cirrhosis, 43 patients with CLD and 27 healthy controls., Results: Patients with cirrhosis compared to non-cirrhotics with CLD had a higher median sCD146 concentration (639 vs. 317 ng/ml). In receiver operating characteristic (ROC) curve analysis, the cut-off of 412 ng/ml showed a sensitivity of 78% and a specificity of 75% for diagnosis of cirrhosis, offering good diagnostic accuracy (area under the ROC curve [AUROC: 0.838]). Patients with compensated compared to those with decompensated cirrhosis had a lower median sCD146 concentration (399 vs. 848 ng/ml, respectively). A cut-off of 534 ng/ml offered a sensitivity of 83% and a specificity of 78% for differentiating compensated from decompensated cirrhosis (AUROC: 0.866). Furthermore, in cirrhotics, sCD146 correlated positively with AST, bilirubin levels and most importantly with international normalized ratio and model for end-stage liver disease (r = 0.648, p < 0.001 and r = 0.567, p < 0.001, respectively)., Conclusion: sCD146 can be used as a surrogate, inexpensive biomarker for the diagnosis of cirrhosis. It is also well correlated with severity of liver disease in cirrhotic patients. Further studies are needed to define its role in clinical practice.

Objectives: Regulatory T cells (Tregs) are inversely correlated to disease activity in systemic lupus erythematosus (SLE). However, little is known concerning the influence of immunosuppressive agents on Tregs, which was the objective of this study., Method: Thirty-five patients with SLE (29 females, six males, mean age 42.4 ± 12.8 years) were included. CD4+CD25(high)FOXP3+ Tregs were prospectively assessed by flow cytometry every month for intravenous (iv) and quarterly for oral regimens. Clinical assessment was made with the SLE Disease Activity Index (SLEDAI). Statistical analysis was performed with a Student's t-test; p < 0.05 was considered significant., Results: In total, 44 cases of SLE relapse were treated with iv cyclophosphamide (CYP, n = 10), iv methylprednisolone (MP, n = 7), iv immunoglobulins (IVIGs, n = 5), oral MP (n = 8), oral MP + azathioprine (AZA, n = 8), and hydroxychloroquine (HCQ, n = 6). CYP, iv MP, and IVIGs resulted in a significant increase in Tregs (4.2 ± 1.6 vs. 10.1 ± 5.7, 2.9 ± 1.3 vs. 10.6 ± 4.8, and 5.6 ± 2.7 vs. 15.2 ± 6.3 cells/mm(3), respectively, p < 0.05). Oral MP, alone or combined with AZA, led to a significant increase in Tregs (7.4 ± 2.5 vs. 11.8 ± 3.8 and 5.1 ± 2.4 vs. 9.4 ± 3.6 cells/mm(3), respectively, p < 0.05), as did HCQ (8.2 ± 2.4 vs. 12.8 ± 2.7 cells/mm(3), p < 0.05). Time to Tregs recovery was significantly shorter with iv MP and IVIGs compared to CYP (1.4 ± 0.5, 1.6 ± 0.9, and 4.0 ± 1.5 months, respectively, p < 0.05)., Conclusions: Increase in Tregs during SLE remission is independent of the therapeutic regimen used and probably represents an epiphenomenon of disease remission. Time to Tregs restoration was significantly shorter in patients treated with iv MP and IVIGs compared to CYP pulse therapy.

Treatment of β-thalassemia major (β-TM) includes regular blood transfusions and iron chelation with subcutaneous injection of deferoxamine (DFO). During the last decade, a new chelation agent, deferiprone (L1), was introduced. The purpose of our study was to determine the level of awareness/education regarding chelation therapy, the degree of compliance to this therapy and their views of L1 in patients with β-TM. A relevant questionnaire was administered to 36 patients (12-26 years old) who were on combination chelation therapy with both DFO and L1. The majority of patients was well aware/educated about chelation therapy (76.6%), was compliant with this therapy (74.4%) and had a positive view towards oral chelation (86.0%). In conclusion, most patients with β-TM who were on combination chelation therapy with DFO and L1 were satisfied with this treatment and this results in high compliance rates.

Background: We investigated the effects of the use of vitamin E-coated membrane (VEM) dialyzer in comparison to simvastatin on markers of chronic inflammation, oxidative stress, and endothelial cell apoptosis in ten patients on chronic hemodialysis (HD), aiming at distinguishing the different treatment effects and their time sequence on these pathogenetic routes., Methods: Ten HD patients were sequentially submitted to a 6-month treatment with the use of VEM and 10 mg of simvastatin daily, interrupted by a 3-month washout period. At baseline, at 3, and 6 months of each trial, serum C-reactive protein (CRP), apolipoprotein (Apo) A1 and B, lipoprotein-a [Lp(a)], high-sensitivity interleukin-6 (hsIL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), soluble Fas (sFas), soluble Fas ligand (sFasL), and plasma oxidized low-density lipoproteins (oxLDL) levels were determined., Results: VEM treatment resulted in a significant decrease in CRP, IL-6, sICAM-1 at 3 months, and oxLDL at 6 months, compared to baseline. Simvastatin resulted in a significant decrease in CRP, which correlated with decreases in both total (r = 0.87, p < 0.05) and low-density lipoprotein cholesterol, IL-6, sICAM-1, sVCAM-1, oxLDL, and sFas at 6 months, compared to baseline. Simvastatin effects on sVCAM-1 (mean difference = 652 ng/mL; 95% CI = 294 to 2686; p < 0.05) and sFas (mean difference = 1284 pg/mL; 95% CI = 510 to 1910; p < 0.05) differed significantly from the corresponding VEM effects., Conclusions: The 6-month use of VEM resulted in more direct and immediate anti-inflammatory effects compared with those caused by the 6-month treatment with simvastatin. Simvastatin caused a more intense decrease in the markers of inflammation, which was in part correlated with its lipid-lowering effects.

Objective: To explore whether the improvement of lipid profile and glycaemic control observed in randomized control trials with pioglitazone (PIO) is replicated under conditions of general clinical practice., Research Design and Methods: We studied 2388 patients with type 2 diabetes (T2DM) not adequately controlled by monotherapy on either metformin (MET) or sulphonylurea (SU). Addition of a second drug, according to the treating physician's choice, resulted in three groups, PIO + MET, PIO + SU and MET + SU, followed for twelve months, while efficacy and safety parameters were measured at baseline, at six and at twelve months., Results: A total of 2116 (88.6%) patients completed the study. Diabetic control and lipid profile improved in all three groups, but the improvement was always greater in the two PIO groups. At 12 months PIO + SU and PIO + MET groups compared to SU + MET showed greater increase in HDL cholesterol (8.3% and 9.2 versus 4.3% p < 0.001) and greater decrease in HbA1c (1.53% and 1.46% versus 0.97%, p < 0.001 for both), in triglycerides (20.7% and 21.5% versus 15.2%, p < 0.001) and in LDL cholesterol (15.2% and 14.6% versus 11.3%, p < 0.001 and p < 0.01, respectively). All changes were greater in patients already taking hypolipidaemic drugs. As ECLA was an observational study, the major limitation is the introduction of confounding bias which, however, was accounted for in the statistical analysis., Conclusions: Since improvement of both glycaemic control and lipid profile are considered main targets in the management of the diabetic patient, the results of the present study, conducted under conditions of everyday clinical practice, show that pioglitazone may be considered a potential choice for the treatment of type 2 diabetes, when lifestyle and metformin fail.

Neuroblastoma is the most common extracranial solid tumor in children. Survival rates have improved due to advances in treatment with aggressive chemotherapy and autologous bone marrow transplantation. Usual sites of recurrence include the site of primary tumor, residual gross disease, bone, bone narrow, liver, and lungs. The authors describe a 16-month-old boy with stage IV extracerebral primary neuroblastoma who died because of an isolated central nervous system (CNS) relapse. The CNS is a rare site of relapse that is, however, increasingly diagnosed due to prolonged survival. Criteria to identify patients at increased risk of CNS relapse are urgently needed. High-risk patients should be followed-up with brain and spine magnetic resonance imaging (MRI) for timely detection of metastases and appropriate management.

Objective: The results of retrospective studies suggest an association between smoking, insulin resistance, steatosis and fibrosis in patients with chronic hepatitis C (CHC); no data are available for chronic hepatitis B (CHB). The purpose of this study was to evaluate the relationship, if any, of such factors on liver fibrosis in a cohort of patients with CHB and CHC., Material and Methods: The study prospectively included 271 consecutive patients with CHB (n=95) or CHC (n=176) who had undergone liver biopsies. Each patient completed a questionnaire on smoking habits; anthropometric measurements and laboratory examinations were carried out and histological lesions were recorded., Results: In CHC patients, severe fibrosis was independently associated with a higher body mass index (BMI) (OR: 1.180, 95% CI: 1.028-1.354; p=0.019), heavy smoking (OR: 3.923, 95% CI: 1.356-11.348; p=0.012), higher alanine aminotransferase (ALAT) levels (OR: 1.010, 95% CI: 1.003-1.017; p=0.005) and alkaline phosphatase (ALP) levels (OR: 1.016, 95% CI: 1.001-1.030; p=0.03) and presence of necroinflammation (OR: 11.165, 95% CI: 1.286-96.970; p=0.029). Moreover, steatosis was independently associated with high gamma-glutamyl transpeptidase (GGT) values, heavy smoking and presence of necroinflammation. In CHB patients, no association between smoking habits and fibrosis or steatosis was noted., Conclusions: Heavy smoking is associated with severe fibrosis in CHC but not CHB. Heavy smoking is also significantly associated with steatosis in CHC and this could be the link between smoking and fibrosis progression.

Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Activating mutations in tyrosine kinase receptors KIT or platelet-derived growth factor receptor alpha (PDGFRA) are the main mechanisms causing the disease. Patients generally present with non-specific symptoms, while a number of tumors are discovered incidentally and may be metastatic at the time of diagnosis. Aggressive GISTs have a defined pattern of metastasis to the liver or throughout the abdomen, or both. Though GISTs rarely present systemic or isolated paraneoplastic reactions, a few cases have been reported in the literature. We present the case of a 54-year-old patient with metastatic GIST at diagnosis and the emergence of paraneoplastic manifestations during follow-up.

Objective: Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity., Material and Methods: We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively., Results: Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035)., Conclusions: Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

Hemophilic pseudotumor is an uncommon complication seen in approximately 1-2% of patients with severe hemophilia. Hemophilic pseudotumors are distinguished into two subdivisions based on location, proximal or distal. Plain x-rays and CT are useful in diagnosis, but MR imaging is the diagnostic test of choice because of its sensitivity to the various blood products. The choice of therapy depends on many parameters, such as the size of the tumor, the age of the patient, and the relation with underlying organs. In most cases of asymptomatic hemophilic pseudotumor, conservative treatment with administration of missing factor as well as immobilization is recommended. The authors describe a 13-year-old boy with severe hemophilia A, who presented with a tibial pseudotumor a few months after an injury. He was conservatively treated for a long period, with daily administration of recombinant factor VIII. His clinical condition improved shortly after therapy induction, but radiological improvement has been moderate. Case history, imaging findings, and therapeutic options are discussed.

Objective: To study the prevalence and predisposing factors of liver involvement in sickle cell disease (SCD) of patients with acute vaso-occlusive crisis., Material and Methods: We prospectively evaluated 41 consecutive patients (44% M, median age 39 years, range 16-56 years) with homozygous (HbSS; 12 cases) or sickle cell-beta thalassemia (HbSbeta-thal; 29 cases), admitted to our Medical Department in the period 2002 to 2004. Severity of crisis was graded by in-house-modified APACHE score; presence of asplenia or functional hyposplenism was also considered. Hematological and biochemical parameters including various relevant enzymes/isoenzymes were followed daily., Results: Despite the fact that only 9 patients (22%) presented with acute painful hepatomegaly, liver involvement was evident in 16 (39%); hepatocellular-type injury was found in 1 patient, cholestatic in 8, and mixed in 7. Severity of crisis was not related to liver involvement (score 20.6 versus 18.2), but liver involvement occurred in the presence of normal spleen function (p<0.001) and platelet counts <500,000/mm(3) (p<0.001) were. Patients with liver involvement, compared with those without, had higher total and direct bilirubin levels (4.3 versus 2.9 mg/dL, p=0.050; 1.9 versus 0.8 mg/dL, p=0.010, respectively), lower hematocrit (19% versus 23%, p=0.030) and longer hospitalization (10 versus 6.3 days, p<0.001)., Conclusions: In SCD, there is a 39% prevalence of acute veno-occlusive involvement of the liver, a figure that is much higher than previously reported. The type of injury is mostly mixed hepatocellular-cholestatic or purely cholestatic and its course is usually benign. Liver involvement occurs more often in patients with normal spleen function and is not associated with the overall severity of the acute episode, both observations being unreported previously.

The increased incidence of multidrug-resistant (MDR) Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients poses a severe therapeutic problem. The aim of this study was to evaluate the efficacy and safety of 2 high-dose treatment regimens of ampicillin-sulbactam (A/S) for MDR Acinetobacter baumannii VAP. We undertook a randomized, prospective trial of critically ill patents with (MDR) Acinetobacter baumannii VAP. Patients were randomly assigned to 1 of 2 treatment regimens of A/S (at a rate 2:1 every 8 h): 1) group A, 18/9 g daily dose (n = 14); and 2) group B, 24/12 g daily dose (n = 13). The duration of therapy was 8+/-2 d for both groups. A total of 27 patients were enrolled in the study. Clinical improvement was seen in 66.7% of the study population in 9/14 (64.3%) of group A patients and 9/13 (69.2%) of group B patients, respectively. Bacteriological success was achieved in 77.8% of the study population (12/14, 85.7% of group A) and in 9/13 (69.2%) of group B patients. The 14-d mortality rate was 25.9% and the all cause 30-d mortality was 48.1%. Both mortality rates did not differ significantly between the 2 groups. No major adverse reactions were recorded. We concluded that clinical and bacteriological results of the study support the use of high-dose regimen of ampicillin-sulbactam for MDR Acinetobacter baumannii VAP.

We present an unusual onset of meningoencephalitis due to VZV reactivation, with increased intrathecal production of IgG VZV antibodies and negative PCR, in a young, immunocompetent adult. Herpes zoster erupted 5 d later. Rare complication of VZV-related rhabdomyolysis occurred, with subsequent ARF, in combination with acyclovir and ceftriaxone. The patient recovered fully and remained healthy.

The case of a 65-year-old woman presenting with Guillain-Barré syndrome is herein reported. Tomographic investigation revealed abdominal and retroperitoneal fibromatosis. During her hospitalization, renal involvement ensued, and subsequent renal biopsy demonstrated findings of crescentic pauci-immune glomerulonephritis negative for ANCA antibodies and with characteristics indicative of necrotic angiitis. The simultaneous existence of the three diseases in the same patient as well as the relation between necrotic vasculitis and G-B syndrome is speculated, and the relevant literature is reviewed.

Strumpell's familial spastic paraplegia is a rare hereditary disease, clinically characterized by progressive disturbance of gait. Focal Segmental Glomerulosclerosis (FSGS) is a frequent glomerulopathy, with an extremely rare familial subtype. The cases of two brothers with Strumpell' s disease are reported, who also developed glomerular renal disease, most probably familial FSGS. The genetics of the two disorders, Strumpell's paraplegia and familial FSGS, are discussed, together with the possibility of a parallel transmission.

Objective: Liver cholestatic enzymes and/or bilirubin occasionally occur in acute stroke and are usually, but not always, ascribed to comorbid conditions. We investigated the frequency and possible etiology of this phenomenon., Material and Methods: Prospective evaluation of post-admission biochemical cholestasis of all patients hospitalized with acute stroke was conducted during a 21-month period., Results: Of 169 consecutive patients, 18 (10.7%) developed cholestasis. In 7 of the patients (4.1%; 4 M, 3 F, median age 70 years, range 57-82 years) no apparent cause of cholestasis could be found, and they were further evaluated (Group A). These patients were compared with 21 randomly selected stroke patients without cholestasis, matched for age and gender, and who acted as controls (Group B). Group A patients were in a deeper coma than the controls (Glasgow Coma Scale 3.4 +/- 0.8 versus 1.9 +/- 0.7, p < 0.001), associated with severe autonomic and hypothalamic involvement, while no such manifestations were present in Group B (p < 0.001). Cholestasis started on the 3rd-6th day and lasted up to the 11th-25th day, with maximum median levels of gamma-GT and serum alkaline phosphatase (SAP) of up to 4.38 (range 2.33-8.25) and 1.49 (range 0.63-2.56) times the upper limit of normal, respectively. Serum alanine aminotransferase (ALAT), total and direct bilirubin increased in Group A but not in Group B. The common bile duct was significantly wider in Group A than in Group B (7.7 +/- 0.5 versus 4.7 +/- 0.6 mm, p < 0.001) and within Group A during and after cholestasis (7.7 +/- 0.5 versus 4.7 +/- 0.5 mm, p < 0.001)., Conclusions: Transient cholestasis may occur in 4.1% of patients following acute stroke. Cholestasis is associated with deeper coma, autonomic and hypothalamic involvement and common bile duct dilatation without obstruction, possibly related to inordinate hypertonia of the sphincter of Oddi.