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Elevated concentrations of soluble urokinase plasminogen activator receptor (suPAR) predict progression to severe respiratory failure (SRF) or death among patients with COVID-19 pneumonia and guide early anakinra treatment. As suPAR testing may not be routinely available in every health-care setting, alternative biomarkers are needed. We investigated the performance of C-reactive protein (CRP), interferon gamma-induced protein-10 (IP-10) and TNF-related apoptosis-inducing ligand (TRAIL) for predicting SRF or death in COVID-19.Two cohorts were studied; one discovery cohort with 534 patients from the SAVE-MORE clinical trial; and one validation cohort with 364 patients from the SAVE trial including also 145 comparators. CRP, IP-10 and TRAIL were measured by the MeMed Key® platform in order to select the biomarker with the best prognostic performance for the early prediction of progression into SRF or death.IP-10 had the best prognostic performance: baseline concentrations 2000 pg/ml or higher predicted equally well to suPAR (sensitivity 85.0 %; negative predictive value 96.6 %). Odds ratio for poor outcome among anakinra-treated participants of the SAVE-MORE trial was 0.35 compared to placebo when IP-10 was 2,000 pg/ml or more. IP-10 could divide different strata of severity for SRF/death by day 14 in the validation cohort. Anakinra treatment decreased this risk irrespective the IP-10 concentrations.IP-10 concentrations of 2,000 pg/ml or higher are a valid alternative to suPAR for the early prediction of progression into SRF or death the first 14 days from hospital admission for COVID-19 and they may guide anakinra treatment.gov, NCT04680949 and NCT04357366.

Introduction Cryptococcal meningoencephalitis is a life-threatening disease affecting mainly immunocompromised hosts. Case report We present a case of a 64-year-old immunocompetent patient, who initially developed a traumatic scalp skin infection due to Cryptococcus neoformans. The patient received oral fluconazole and subsequently liposomal amphotericin B due to the development of resistance with resolution of the infection. Two years later, during chemotherapy for newly diagnosed gastric and lung cancer, he developed fulminant cryptococcal meningoencephalitis, which did not respond to liposomal amphotericin B and flucytosine. Conclusions To our knowledge, this is the first case of fulminant cryptococcal meningoencephalitis following long latency after adequately treated primary cutaneous infection.

Background Listeria monocytogenes is an opportunistic pathogen that causes severe infections of the Central Nervous System, such as meningitis or meningoencephalitis, and brain abscesses. Abscesses account for approximately 1-10% of CNS listerial infections and are observed in 1% of all listerial infections. Methods We describe a case of 70-year-old male patient who had several admissions in different hospitals over the last 8 weeks. Results He suffered from intermittent fever for over a month, recurrent episodes of headaches, disorientation and other neurological symptoms. His condition was misdiagnosed as giant cell arteritis and initially the patient was started on corticosteroids. MRI of the brain revealed the presence of multiple brain abscesses and the cerebrospinal fluid study confirmed the presence of Listeria Monocytogenes. The patient was started on ampicillin and he completed a 6 weeks' course of treatment. Conclusions This case emphasizes the need to include rare pathogens in the differential diagnosis when possible CNS infections are involved, as well as to show that in many cases some auto-immune diseases are overdiagnosed.

Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any correlations to joint hypermobility (JH).Fifty patients (31 males, 19 females) with vasomotor symptoms enrolled in this five-year prospective observational study. Clinical examination by a rheumatologist and a vascular surgeon was performed along with cardiology, echocardiographic and Doppler evaluation. Patients underwent blood cell count, biochemistry, thyroid and selectively immunologic testing. Twenty-four (48%) of them performed nailfold capillaroscopy. The SPSS for Windows, v.17.0, Chicago, USA, was used for the statistical analyses.Twenty-eight patients (56%) presented with erythromelalgia (EM), 6 (12%) with acrocyanosis (AC) and 9 (18%) as a combination of the above disorder. RP diagnosed in five (10%) while two patients (4%) presented as a mix of EM-RP. There was no correlation with abnormal laboratory tests. Increased incidence of JH was found in EM and AC patients. Among those who were tested with nailfold capillaroscopy, 75% had abnormalities ranged from mild to autoimmune-like diseases.Erythromelalgia is the commonest functional vasculopathy in young population followed by acrocyanosis and a combination of these conditions. Joint hypermobility is markedly increased, indicating that dysautonomy may be considered the causative factor following a trigger event. Overall, RP was observed in 14% of patients. Clinical recognition of these disorders avoids unnecessary investigation. Key Points • Vascular acrosyndromes in young adults are commonly functional disorders resembling vascular algodystrophy induced by thermic stress. • Dysautonomy of joint hypermobility is the co-factor influencing the appearance of the vascular disorders. • Raynaud's phenomenon accounts to approximately 14% of vascular acrosyndromes presented in the young adult population.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but several develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from C-reactive protein, D-dimer, interleukin-6, and ferritin circulating concentrations at hospitalization during the SAVE-MORE study, offers comparable predictive accuracy for progression to SRF or death within 14 days as suPAR ≥6 ng/ml (area under receiver operator characteristic curve, 0.81 for both). SCOPE score was validated against an independent dataset from the SAVE study. The SCOPE score is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions. Funding: The study was funded in part by the Hellenic Institute for the Study of Sepsis and by Swedish Orphan Biovitrum. The Hellenic Institute for the Study of Sepsis is the Sponsor of the SAVE and SAVE-MORE studies. Declaration of Interests:E. J. Giamarellos-Bourboulis has received honoraria from Abbott CH, bioMerieux, Brahms GmbH, GSK, InflaRx GmbH, Sobi and XBiotech Inc; independent educational grants from Abbott CH, AxisShield, bioMerieux Inc, InflaRx GmbH, Johnson & Johnson, MSD, Sobi and XBiotech Inc.; and funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis). G. Poulakou has received independent educational grants from Pfizer, MSD, Angelini, and Biorad. H. Milionis reports receiving honoraria, consulting fees and non-financial support from healthcare companies, including Amgen, Angelini, Bayer, Mylan, MSD, Pfizer, and Servier. L. Dagna had received consultation honoraria from SOBI. M. Bassetti has received funds for research grants and/or advisor/consultant and/or speaker/chairman from Angelini, Astellas, Bayer, Biomerieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer, Roche, Shionogi and Nabriva. P. Panagopoulos has received honoraria from GILEAD Sciences, Janssen, and MSD. G. N. Dalekos is an advisor or lecturer for Ipsen, Pfizer, Genkyotex, Novartis, Sobi, received research grants from Abbvie, Gilead and has served as PI in studies for Abbvie, Novartis, Gilead, Novo Nordisk, Genkyotex, Regulus Therapeutics Inc, Tiziana Life Sciences, Bayer, Astellas, Pfizer, Amyndas Pharmaceuticals, CymaBay Therapeutics Inc., Sobi and Intercept Pharmaceuticals. M. G. Netea is supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. Hes is a scientific founder of TTxD and he has received independent educational grants from TTxD, GSK, Ono Pharma and ViiV HealthCare. The other authors do not have any competing interest to declare. Ethics Approval Statement: The SAVE protocol was approved by the National Ethics Committee of Greece (approval 38/20) and National Organization for Medicines approval (ISO 28/20). The SAVE-MORE protocol was approved by the National Ethics Committee of Greece (approval 161/20) and by the Ethics Committee of the National Institute for Infectious Diseases Lazzaro Spallanzani, IRCCS, in Rome (1 February 2021). Trial Registration: The SAVE study was prospectively registered prior to enrolling the first patient (EudraCT number 2020-001466-11; ClinicalTrials.gov identifier NCT04357366). The SAVE-MORE study was prospectively registered (EudraCT no. 2020-005828-11; ClinicalTrials.gov identifier NCT04680949). Written informed consent was provided by all patients prior to enrollment.

Most patients infected with SARS-CoV-2 (COVID-19) experience mild, non-specific symptoms, but many develop severe symptoms associated with an excessive inflammatory response. Elevated plasma concentrations of soluble urokinase plasminogen activator receptor (suPAR) provide early warning of progression to severe respiratory failure (SRF) or death, but access to suPAR testing may be limited. The Severe COvid Prediction Estimate (SCOPE) score, derived from circulating concentrations of C-reactive protein, D- dimers, interleukin-6, and ferritin among patients not receiving non-invasive or invasive mechanical ventilation during the SAVE-MORE study, offers predictive accuracy for progression to SRF or death within 14 days comparable to that of a suPAR concentration of ≥6 ng/mL (area under receiver operator characteristic curve 0.81 for both). The SCOPE score is validated in two similar independent cohorts. A SCOPE score of 6 or more is an alternative to suPAR for predicting progression to SRF or death within 14 days of hospital admission for pneumonia, and it can be used to guide treatment decisions.

The median arcuate ligament, or celiac artery compression syndrome is a rare syndrome, caused by extrinsic compression of the celiac trunk by the median arcuate ligament. Its symptomatology mainly comprises of visceral angina. Differential diagnosis includes cardiovascular angina, other vascular events and causes of vagotonia. The case reported here refers to a middle aged male patient who presented with intermittent epigastric pain and diaphoresis after a long drive. Diagnosis was made radiologically, during computed tomography scan angiography, which revealed a hook-like appearance of the celiac artery partially loosened during inspiration. Careful history and cautious reviewing of the imaging may refrain from further, unnecessary, diagnostic investigations., Internal medicine, Emergency medicine, Medical imaging; Biological sciences; Health sciences; Visceral angina, Median arcuate ligament, Celiac artery compression syndrome.

Baseline chest computed tomography (BCT) in high-risk hematology patients allows for the early diagnosis of invasive pulmonary aspergillosis (IPA). The distribution of BCT implementation in hematology departments and impact on outcome is unknown. A web-based questionnaire was designed. International scientific bodies were invited. The estimated numbers of annually treated hematology patients, chest imaging timepoints and techniques, IPA rates, and follow-up imaging were assessed. In total, 142 physicians from 43 countries participated. The specialties included infectious diseases (n = 69, 49%), hematology (n = 68, 48%), and others (n = 41, 29%). BCT was performed in 57% (n = 54) of 92 hospitals. Upon the diagnosis of malignancy or admission, 48% and 24% performed BCT, respectively, and X-ray was performed in 48% and 69%, respectively. BCT was more often used in hematopoietic cell transplantation and in relapsed acute leukemia. European centers performed BCT in 59% and non-European centers in 53%. Median estimated IPA rate was 8% and did not differ between BCT (9%, IQR 5&ndash, 15%) and non-BCT centers (7%, 10%) (p = 0.69). Follow-up computed tomography (CT) for IPA was performed in 98% (n = 90) of centers. In high-risk hematology patients, baseline CT is becoming a standard-of-care. Chest X-ray, while inferior, is still widely used. Randomized, controlled trials are needed to investigate the impact of BCT on patient outcome.

Aim No randomized study has been conducted to investigate the use of intravenous paracetamol (acetaminophen, APAP) for the management of fever due to infection. The present study evaluated a new ready-made infusion of paracetamol. Methods Eighty patients with a body temperature onset ≥38.5°C in the previous 24 h due to infection were randomized to a single administration of placebo (n = 39) or 1 g paracetamol (n = 41), and their temperature was recorded at standard intervals. Rescue medication with 1 g paracetamol was allowed. Serum samples were collected for the measurement of APAP and its metabolites. The primary endpoint was defervescence, defined as a core temperature ≤37.1°C. Results During the first 6 h, defervescence was achieved in 15 (38.5%) patients treated with placebo compared with 33 (80.5%) patients treated with paracetamol 1 g (P < 0.0001). The median time to defervescence with paracetamol 1 g was 3 h. Rescue medication was given to 15 (38.5%) and five (12.2%) patients allocated to placebo and paracetamol, respectively (P = 0.007); nine (60.0%) and two (40.0%) of these patients, respectively, experienced defervescence. No further antipyretic medication was needed for patients becoming afebrile with rescue medication. Serum glucuronide-APAP concentrations were significantly greater in the serum of patients who did not experience defervescence with paracetamol. The efficacy of paracetamol was not affected by serum creatinine. No drug-related adverse events were reported. Conclusions The 1 g paracetamol formulation has a rapid and sustainable antipyretic effect on fever due to infection. Its efficacy is dependent on hepatic metabolism.

Quality of life (QoL) is a complex outcome and rheumatologic patients typically exhibit several comorbidities with a negative impact. In this study, we analyzed with respect to QoL for the first time a wide range of physical and psychological factors, including individual, clinical and disease-related parameters, mental health disorders, sexual dysfunction, and cardiovascular comorbidities among consecutive rheumatologic patients. QoL was evaluated using the EuroQol 5D (EQ-5D) utility index. The Health Assessment Questionnaire (HAQ) Disability Index, and the HAQ Pain Visual Analogue Scale were used as measures of physical disability and arthritis-related pain, respectively. The Hamilton Anxiety Scale and Zung Self-Rating Depression Scale, the International Index of Erectile Function and the Female Sexual Functioning Index were completed by all patients. In total, 360 patients were included, 301 females and 59 males. In the univariate analysis, pain, physical disability (p

Objective:Elevated blood pressure (BP) in the acute phase of ischemic stroke is associated with heightened risk of early disability and death. However, whether BP-lowering in the acute post-stroke period is beneficial and the exact levels at which BP should be targeted remain unclear. This study aim

Rheumatoid arthritis is a systemic autoimmune disease resulting in joint destruction and deformities, but also associated with extraarticular and systemic manifestations. The later devastating conditions, such as the development of rheumatoid vasculitis, are more frequently encountered in seropositive patients and their incidence has been attenuated after the introduction of biologic disease modifying drugs, such as anti-tumor necrosis factor alpha (TNFa) agents, which generally have considerably contributed to the better control and long-term outcomes of the disease. Interestingly, autoimmune syndromes may, rarely, present in patients without a positive history after the initiation of treatment. We present a rare case of a woman with seronegative rheumatoid arthritis who developed pyoderma gangrenosum whistle on treatment with golimumab, a fully humanized anti TNFa antibody. The recording of this as well as analogous paradoxical autoimmune syndromes in association with the individual patient characteristics will render treating physicians aware of potential adverse reactions and assist in the understanding of the cytokine driven pathophysiological mechanisms underlying these disorders.

Introduction Sexual functioning may be notoriously affected in patients suffering from rheumatic diseases, yet the extent to which physical and/or psychological factors contribute to sexual dysfunction in this particular group of patients remains underinvestigated. Aim This cross-sectional study aimed at investigating whether an association exists between psychological status (anxiety, depression) and sexual dysfunction, independently of other physical factors, in patients with rheumatic disorders. Methods A total of 509 consecutive rheumatologic patients, aged 54.7 ± 14.2 years, 423 female and 86 male, were studied. Female and male sexual function was evaluated with the Female Sexual Dysfunction Index (FSFI) and the International Index of Erectile Function (IIEF) questionnaire, respectively. The Hamilton Anxiety Scale and the Zung Self-Rating Depression Scale were used to detect presence of anxiety and depression, respectively. Main Outcome Measures Sexual dysfunction affected 69.9%, anxiety 37.5%, and depression 22% of our patients. Results A strong and negative correlation was found between anxiety and both FSFI (r = −0.169, P P = 0.004). Similarly, depressive symptomatology was strongly and negatively correlated with both FSFI (r = −0.178, P P = 0.04). In the logistic regression analysis, apart from increasing age and female sex, depression ( P = 0.027) and anxiety ( P = 0.049) were identified as the only predictors of sexual dysfunction, even after adjustment for a variety of physical factors. Conclusions Mental distress and sexual dysfunction are extremely common in rheumatologic patients. Sexual dysfunction is significantly associated with anxiety and depression in both men and women and may be independently predicted by their presence in this group of patients. Physicians dealing with rheumatologic patients should be aware of these results and incorporate screening and treatment of the above comorbidities in the global assessment of their patients, in order to alleviate the disease-emerging mental and physical burden and improve their quality of life. Anyfanti P, Pyrpasopoulou A, Triantafyllou A, Triantafyllou G, Gavriilaki E, Chatzimichailidou S, Gkaliagkousi E, Petidis K, Aslanidis S, and Douma S. Association between mental health disorders and sexual dysfunction in patients suffering from rheumatic diseases. J Sex Med 2014;11:2653–2660.

Early identification of hypertensive target organ damage (TOD) emerges as important for global cardiovascular risk assessment. Retinal vascular alterations, capillary rarefaction, and microalbuminuria represent different forms of microvascular TOD. However, data regarding their concomitant presence in the early stages of hypertension, the association of the number of affected organs with cardiovascular risk, and aldosterone effect on multiple TOD are lacking. We studied naive, never-treated patients with recent duration of hypertension and healthy volunteers. Innovative software was developed to estimate retinal vascular diameters and capillary density. Biochemical parameters including microalbuminuria and serum aldosterone were derived. Framingham Risk Score was used to determine cardiovascular risk. In total 103 subjects, 66 hypertensives and 37 normotensives, were included. Hypertensive patients exhibited a greater number of affected target organs compared with normotensives (P = .014), with retinopathy and capillary rarefaction (40.9%) representing the most common TOD among hypertensives. The number of affected organs was linearly correlated with increased Framingham score and serum aldosterone, analyzed with univariate (P < .001 and P = .002) and multivariate analysis (P = .025 and P = .004), respectively. Physicians dealing with hypertensive patients should be aware of the possibility of diffuse microvascular impairment and seek multiple TOD even in the early stages of hypertension.

BACKGROUND Although impairment of the micro- and macrocirculation is considered inherent to sustained hypertension, there is a substantial lack of studies investigating whether an association exists between micro- and macrovascular damage, especially in early-stage hypertension. METHODS We studied a meticulously selected population, free of diabetes and cardiovascular disease, of 223 individuals: 137 never-treated, newly diagnosed patients with recent onset of hypertension and 86 normotensive individuals. Nonmydriatic retinal photography was used to assess retinal microvascular diameters, including central retinal arteriolar (CRAE) and venular equivalent and arteriovenous ratio (AVR). Arterial stiffness was evaluated by measurement of pulse wave velocity (PWV) and aortic augmentation index (AIx). RESULTS Compared with normotensive subjects, hypertensive patients exhibited significantly increased PWV (8.1 vs. 7.1 m/sec; P < 0.001) and AIx (23.86% vs. 18.8%; P = 0.01) and decreased CRAE (86.47 vs. 91.44 μm; P = 0.001) and AVR (0.74 vs. 0.78; P = 0.007). A significant inverse association was demonstrated between PWV and CRAE (r = -0.205; P = 0.002), which remained significant after multivariable analysis. Likewise, CRAE (P = 0.04) and AVR (P = 0.02) were independent predictors of AIx. CONCLUSIONS This study shows for the first time an association between quantitatively assessed retinal abnormalities and increased arterial stiffness in a sample of early-stage hypertensive and normotensive individuals, suggesting that micro- and macrocirculation impairment in hypertension is a dynamic, mutual, interdependent process present from its very early stages. Given the predictive value of both retinal arteriolar narrowing and arterial stiffness in terms of cardiovascular mortality and morbidity, identification of combined micro- and macrovascular damage might be helpful in cardiovascular risk stratification of hypertensive patients.

Nephritis represents a frequent, severe complication of systemic lupus erythematosus. Autoantibodies appear to be fundamental in the pathogenesis of lupus nephritis. Several hypotheses are currently experimentally tested to further elucidate the direct induction of inflammation through interaction of the pathological autoantibodies with intrinsic glomerular components and the triggering of a complement-driven autoinflammatory cascade. B-cells have, in the last decade, emerged as a promising new therapeutic target, as biological treatments successfully attempting B-cell depletion, inhibition of B-cell proliferation and differentiation, or modulation of B-cell function have become bioengineered. Clinical trials have so far proved controversial regarding the efficacy of these new agents. Thus, despite the short and long-term side effects associated with immunosuppressive treatment alternative emerging treatments are still regarded “rescue” regimens in refractory patients. In an effort to accurately evaluate the potential of these therapies in lupus nephritis, several issues have been raised mainly in terms of patient selection criteria and trial duration. This review aims to expand on the proposed pathophysiologic mechanisms implicating the B-cell pathway in the pathogenesis of lupus nephritis and summarize current knowledge obtained from clinical trials introducing these biologics in its treatment. Finally, it will elaborate on potential applications of currently available biologic agents and forthcoming treatment options.

Parvovirus B19 infection has been associated with a variety of rheumatic manifestations/diseases, mainly rheumatoid arthritis, vasculitis and systemic lupus erythematosus (SLE). B19 infection may simulate both clinical and laboratory features of SLE, presenting either as a potential first time diagnosis of SLE or as an exacerbation of previously established disease. The similarities in both clinical and serological features of parvovirus infection and SLE at presentation may hinder the differential diagnosis between these two conditions. Hence, parvovirus B19 infection mimicking SLE usually fulfils

Arterial hypertension represents a leading cause of cardiovascular mortality and morbidity worldwide through its detrimental effects on target organs. Therefore, the early identification and appropriate management of high-risk patients emerges as extremely important. Given that the microvasculature is subject to a series of morphological and functional changes under the continuous effect of high blood pressure, research over the last years has gradually moved toward the identification of specific microcirculatory alterations that may serve as early prognostic markers of cardiovascular risk. Dermal capillaries represent an “open window” for the in vivo study of human microcirculation that has been long used mainly for the study of rheumatic diseases. However, capillaroscopy has been relatively understudied and only recently applied in the field of hypertension. Capillaroscopy represents a forthcoming promising estimate of the microvascular status in hypertensive patients, with capillary rarefaction representing the most typical finding. The present review aims at summarizing available evidence and the main findings, as well as the premises and promises, of capillary rarefaction as a tool for evaluating patients with hypertension.

The B-cell-activating factor (BAFF), a member of the tumor necrosis factor (TNF) family, has recently attracted attention as a potent cytokine, involved in B-cell stimulation and survival of autoimmune cells. Despite its significance in the pathogenesis of autoimmune diseases, data is limited and inconclusive regarding its expression in different stages of rheumatoid arthritis (RA). The aim of this study was to assess BAFF in biologic-naïve RA patients with early versus established disease and monitor its levels in response to anti-TNF treatment in seronegative- and seropositive patients. Based on our results, B-cell-activating factor (BAFF) did not appear to be overexpressed or differentially expressed early (≤2 years duration) in comparison to established rheumatoid arthritis (RA). Moreover, tumor necrosis factor (TNF) blockade did not appear to affect BAFF levels in either seropositive or seronegative RA patients, despite the association of anti-TNF treatment with the development of autoantibodies and the known anti-apoptotic effects of BAFF. As expected, BAFF became induced after B-cell depletion. Investigation of the effect of different biologics on the expression of BAFF and other cytokines will help elucidate the interconnecting immune pathways involved in the initiation and perpetuation of the inflammatory process.

Background/aims The catalytic subunit of human telomerase (hTERT) is known to be expressed in a variety of malignant tumours, including hepatocellular carcinoma (HCC). We studied hTERT expression in regenerative and precancerous lesions arising in cirrhosis. Methods/results As shown by in situ hybridisation, hTERT mRNA was absent in normal liver, but present in varying numbers of hepatocytes and HCC cells of diseased livers, as well as in biliary epithelial cells, lymphocytes, sinusoidal-lining cells and tumour endothelial cells. RT-PCR for two hTERT transcript regions demonstrated hTERT expression in 11 out of 15 cirrhotic liver samples, in 20 out of 21 large regenerative nodules/low-grade dysplastic nodules, in 5 out of 5 high-grade dysplastic nodules, and in 4 out of 4 HCCs. The beta-splice variant was identified in all hTERT-positive cases, while the corresponding full-length transcript was found only in 13 out of 29 positive large nodular lesions and in 4 out of 11 positive cirrhotic samples. The full-length transcript was always found in the presence of the beta-splice variant, usually in low relative levels, and tended to correlate with telomerase activity in the samples, while the beta-splice variant did not. Conclusions This study shows that hTERT re-expression takes place both in hepatic regeneration occurring in cirrhosis and in the early steps of hepatocarcinogenesis, and involves mainly the beta-splice variant of this molecule. Additional regulatory mechanisms may be required for the expression of the full-length hTERT transcript.

A growing amount of literature has explored mainly the role of depression (and/or anxiety) in patients with rheumatic disorders. We aimed at determining the prevalence of depression, anxiety, and their association with quality of life among patients attending a rheumatology clinic, focusing on data regarding concomitant psychiatric treatment. Depression, anxiety, and quality of life were assessed using the Zung Self-Rating Depression Scale, the Hamilton Anxiety Scale, and the Health Assessment Questionnaire, respectively. Overall, 514 rheumatologic patients were studied. Depression and anxiety were documented in 21.8 and 30.8 % of the population, respectively, and correlated significantly with quality of life. Only 13.4 % of patients with depressive symptoms and 12.1 % of patients with anxiety symptoms were receiving antidepressant or antianxiety medication. Given the wide therapeutic armamentarium available nowadays for the management of depression and anxiety, an increased awareness among physicians dealing with rheumatologic patients is warranted in order to integrate detection and effective treatment of anxiety and depression into the routine clinical practice. Special attention should be paid to female patients, patients with longer disease duration, and/or those with established disability.

Gastrointestinal involvement is frequent in patients with systemic lupus erythematosus (SLE). Eosinophilic gastroenteritis, however, has only rarely been described in rheumatological conditions, despite its reported connection to autoimmune diseases, such as hypereosinophilic syndrome, vasculitides, and systemic mastoidosis. It presents typically with abdominal pain and diarrhea and is only exceptionally associated with ascites. Diagnosis can be problematic, as several other clinical conditions (malignancies, infection/tuberculosis, and inflammatory bowel diseases) have to be ruled out. It is basically a nonsurgical disease, with excellent recovery on conservative treatment. We report the rare case of a young woman with overlap syndrome who presented with abdominal pain and ascites. The diagnosis of eosinophilic enteritis was made based on clinical, radiological, and laboratory criteria. The patient was treated with corticosteroids with excellent response.

The issue of fertility and fecundity in female patients with chronic inflammatory arthitides involves, besides sexual dysfunction [1], a higher rate of gynaecological disease, metrorrhagias, ovaria...

We have studied nuclear envelope disassembly in mammalian cells by morphological methods. The first signs of nuclear lamina depolymerization become evident in early prophase as A-type lamins start dissociating from the nuclear lamina and diffuse into the nucleoplasm. While B-type lamins are still associated with the inner nuclear membrane, two symmetrical indentations develop on antidiametric sites of the nuclear envelope. These indentations accommodate the sister centrosomes and associated astral microtubules. At mid- to late prophase, elongating microtubules apparently push on the nuclear surface and eventually penetrate the nucleus. At this point the nuclear envelope becomes freely permeable to large ligands, as indicated by experiments with digitonin-treated cells and by the massive release of solubilized A-type lamins into the cytoplasm. At the prophase/prometaphase transition, the B-type lamina is fragmented, but ‘islands’ of lamin B polymer can still be discerned on the tips of congressing chromosomes. Finally, at metaphase, the lamin B polymer breaks down into small pieces, which tend to concentrate in the area of the mitotic spindle. Nuclear envelope breakdown is not prevented when the microtubules are depolymerized by nocodazole; however, the mode of nuclear lamina fragmentation in the absence of microtubules is markedly different from the normal one and involves multiple raffles and gaps, which develop rapidly along the entire surface of the nuclear envelope. These data suggest that nuclear envelope disassembly is a stepwise process in which the microtubules play an important part.

Sir, The close association between diabetes mellitus and cardiovascular disease is well known, the risk of cardiovascular disease being 2–5 times greater in diabetics than in the background population.1 Renal arteries seem to be widely involved in the macrovascular disease of diabetes, and primary aldosteronism is also a well-recognized cause of secondary hypertension. We report a diabetic woman presenting with refractory hypertension, who had coexisting bilateral atherosclerotic renal artery stenosis and aldosteronism due to bilateral adrenal hyperplasia. A 58-year-old woman was admitted to our Department because of refractory hypertension during the last 4 months, superimposed on pre-existing and poorly controlled hypertension. The patient was completely asymptomatic. There was a 10-year history of hypertension and type 2 diabetes mellitus. Her medications comprised atenolol, irbesartan, hydrochlorothiazide, amlodipine, terazosin, ticlopidine, metformin, and glibenclamide. Blood pressure was 230/100 mmHg, equal in both arms, and the pulse was 80 bpm. On physical examination, renal bruits were heard bilaterally. Twenty-four-hour blood pressure monitoring confirmed marked hypertension and also showed extreme dipping during night-time. On admission, the laboratory values included Ht 31.8%, Hb 10.4 g/dl, MCV 83.0 fl, MCH 27.3 pg, MCHC 32.8 g/dl, potassium 4.3 mmol/l, glucose 288 mg/dl, urea 57 mg/dl, creatinine 1.28 mg/dl, HbA1c 8.6%, total cholesterol 258 mg/dl, LDL cholesterol 169 mg/dl, HDL cholesterol 60 mg/dl, and triglycerides 144 mg/dl. Her urine was positive (++) …

A probable case of decompression illness with associated cutis marmorata is presented, which regressed over a few hours with oxygen breathing and after intravenous methylprednisolone and fluid resuscitation without recompression. He was eventually transferred for hyperbaric treatment some 10 hours post dive. Cutaneous decompression illness is not associated with high mortality per se, but prompt and accurate recognition is warranted, as it may represent a prodromal feature of potentially life-threatening complications. However, in this case, as differential diagnosis, an allergic reaction remains possible.

Hypertensive patients with retinal arteriolar abnormalities are at increased risk for cardiovascular events. However, the extent of retinal microvascular changes in naïve, never-treated patients with hypertension of short duration has not been established. In addition to this, the lack of relevant data about other phenotypes of hypertension (masked and white-coat hypertension) determined by ambulatory blood-pressure measurement (ABPM) is notable, despite their relationship to increased cardiovascular risk mediated by underlying target-organ and vascular damage.We conducted a study in which nonmydriatic retinal photography was used to assess central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) diameters and the retinal arteriovenus ratio (AVR) in a group of 103 individuals with never-treated hypertension of recent (1 year) appearance, 28 individuals with masked and 20 with white-coat hypertension, and 50 normotensive individuals, as appropriately classified by ABPM.Patients with sustained and masked hypertension had narrower values of CRAE than did normotensive individuals (86.7±10.1 and 87.6±9.2 vs. 94.8±10.6, P0.001 and P = 0.02, respectively). The AVR was lower in patients with sustained hypertension (0.736±0.102), masked hypertension (0.716±0.123), and white-coat hypertension (0.739±0.127) than in normotensive subjects (0.820±0.095), P0.001, P0.001, and P = 0.03, respectively. Both AVR and CRAE were negatively associated with mean systolic and diastolic daytime, nighttime, and 24-hour blood pressures, even after adjustment for other factors.Subtle retinal microvascular signs of pathology are observed in hypertensive patients at early stages of hypertension and in patients with both masked and white coat hypertension. These changes may be indicative or may mediate the differences in cardiovascular mortality in persons with masked and white-coat hypertension, and relevant information about this can be easily accessed with retinal photography.