Use of tocilizumab in amyloid a nephropathy associated with Sweet syndrome: a case report and literature review.

Amyloid A nephropathy is a possible complication of chronic inflammatory disease. Proteinuria and kidney failure are the main features of the disease. Tocilizumab (TCZ), an IL6-R antibody approved for rheumatoid arthritis, is a promising choice for histologically demonstrated nephropathy. We describe a case of kidney amyloid associated with Sweet syndrome treated with TCZ. The patient was affected by Sweet syndrome associated with proteinuria. Kidney biopsy showed amyloid deposits. During the follow-up, cutaneous and renal findings were refractory to many immunosuppressive regimen (cyclophosphamide, leflunomide, interferon and steroid). After few years, the patient developed rapidly progressive nephropathy associated with nephrotic syndrome (proteinuria up to 6 g/die). A second kidney biopsy was performed and it showed worsening of amyloid nephropathy. Thus, TCZ was administrated (8 mg/kg once a month) and it stabilized kidney function and induced partial remission of the nephrotic syndrome in the following 2 years.

Cryoglobulinemic vasculitis in primary Sjögren's Syndrome: Clinical presentation, association with lymphoma and comparison with Hepatitis C-related disease.

OBJECTIVE: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. METHODS: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. RESULTS: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. CONCLUSION: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.

COVID-19 and renin-angiotensin system inhibition: role of angiotensin converting enzyme 2 (ACE2) - Is there any scientific evidence for controversy?

Renin-angiotensin system (RAS) blockers are extensively used worldwide to treat many cardiovascular disorders, where they are effective in reducing both mortality and morbidity. These drugs are known to induce an increased expression of angiotensin-converting enzyme 2 (ACE2). ACE2 acts as receptor for the novel SARS coronavirus-2 (SARS-CoV-2) which raising the important issue of possible detrimental effects that RAS blockers could exert on the natural history and pathogenesis of the coronavirus disease-19 (COVID-19) and associated excessive inflammation, myocarditis and cardiac arrhythmias. We review the current knowledge on the interaction between SARS-CoV-2 infection and RAS blockers and suggest a scientific rationale for continuing RAS blockers therapy in patients with COVID-19 infection.

MDCT of blunt renal trauma: imaging findings and therapeutic implications.

OBJECTIVES: To show the wide spectrum of computed tomography (CT) findings in blunt renal trauma and to correlate them with consequent therapeutic implications. METHODS: This article is the result of a literature review and our personal experience in a level II trauma centre. Here we describe, discuss and illustrate the possible CT findings in blunt renal trauma, and we correlate them with the American Association for the Surgery of Trauma (AAST) classification and their therapeutic implications. RESULTS: CT findings following blunt renal trauma can be grouped into 15 main categories, 12 of them directly correlated with the AAST classification and 3 of them not mentioned in it. Non-operative management, which includes the "watchful waiting" approach, endourological treatments and endovascular treatments, is nowadays widely adopted in blunt renal trauma, and surgery is limited to haemodynamically unstable patients and a minority of haemodynamically stable patients. CONCLUSIONS: The interpretation of CT findings in blunt renal trauma may be improved and made faster by the knowledge of their therapeutic consequences. TEACHING POINTS: • The majority of blunt renal injuries do not require surgical treatment. • CT findings in blunt renal injury must be evaluated considering their therapeutic consequences. • Some CT findings in blunt renal trauma are not included in the AAST classification.

The P2X7 receptor-inflammasome complex has a role in modulating the inflammatory response in primary Sjögren's syndrome.

OBJECTIVE: Innate and adaptive immunity may contribute to gland dysfunction in patients with primary Sjögren's syndrome (pSS). The P2X7 receptor (P2X7 R)-NLRP3 inflammasome complex modulates the release of the inflammatory cytokines IL-1ß and IL-18. The presence of P2X7 R in salivary glands suggests an interesting scenario for the initiation and amplification of the innate immune response in pSS. Therefore, the aim of this study was to assess the role of the P2X7 R-NLRP3 inflammasome in pSS. SUBJECTS AND METHODS: Twenty-one consecutive patients with pSS according to the American-European Consensus Group criteria and 15 patients with sicca syndrome (i.e. without Sjögren's syndrome, non-SS) were enrolled in this study, together with six control (CTL) subjects. Expression of the P2X7R-NLRP3 platform and IL-18 was determined by real-time PCR and western blotting in gland specimens and peripheral lymphomonocytes; data were related to patients\x92 clinical, serological and histopathological characteristics. The presence of IL-18 was determined in gland and saliva samples. RESULTS: P2X7 R expression was significantly higher in salivary glands from individuals with pSS than in those from non-SS and CTL subjects. Accordingly, the gene expression levels of the inflammasome components NLRP3, ASC and caspase-1 were significantly higher in pSS gland specimens, and this was paralleled by an increased expression of mature IL-18 in pSS saliva samples. The expression of both the P2X7 R and the inflammasome components was a marker of disease-related glandular involvement, being increased in patients with anti-Ro/SSA positivity and correlated with focus score. CONCLUSION: The results of this study suggest an involvement of the P2X7 R-inflammasome-caspase-1-IL-18 axis in the development of pSS exocrinopathy. This finding provides the basis for studying the complex mechanisms underlying pSS, as well as for developing novel potential therapeutic strategies.

Luminosity-independent measurement of the proton-proton total cross section at √s=8 TeV.

The TOTEM collaboration has measured the proton-proton total cross section at √s=8 TeV using a luminosity-independent method. In LHC fills with dedicated beam optics, the Roman pots have been inserted very close to the beam allowing the detection of ~90% of the nuclear elastic scattering events. Simultaneously the inelastic scattering rate has been measured by the T1 and T2 telescopes. By applying the optical theorem, the total proton-proton cross section of (101.7±2.9) mb has been determined, well in agreement with the extrapolation from lower energies. This method also allows one to derive the luminosity-independent elastic and inelastic cross sections: σ(el)=(27.1±1.4) mb; σ(inel)=(74.7±1.7) mb.

Double diffractive cross-section measurement in the forward region at the LHC.

The first double diffractive cross-section measurement in the very forward region has been carried out by the TOTEM experiment at the LHC with a center-of-mass energy of sqrt[s]=7 TeV. By utilizing the very forward TOTEM tracking detectors T1 and T2, which extend up to |η|=6.5, a clean sample of double diffractive pp events was extracted. From these events, we determined the cross section σDD=(116±25) µb for events where both diffractive systems have 4.7<|η|min<6.5.

Biomarkers of metabolic syndrome and its relationship with the zinc nutritional status in obese women.

INTRODUCTION: Obesity is a chronic disease that induces risk factors for metabolic syndrome and, is associated with disturbances in the metabolism of the zinc. Therefore, the aim of this study was to investigate the existence of relationship between the biomarkers of metabolic syndrome and the zinc nutricional status in obese women. METHOD: Seventy-three premenopausal women, aged between 20 and 50 years, were divided into two groups: case group, composed of obese (n = 37) and control group, composed of no obese (n = 36). The assessment of the body mass index and waist circumference were carried out using anthropometric measurements. The plasmatic and erythrocytary zinc were analyzed by method atomic absorption spectrophotometry (λ = 213.9 nm). RESULTS: In the study, body mass index and waist circumference were higher in obese women than control group (p < 0.05). The mean plasmatic zinc was 72.2 ± 9.0 µg/dl in obese women and 73.4 ± 8.5 µg/dl in control group (p > 0.05). The mean erythrocytary zinc was 36.4 ± 15.0 µg/gHb and 45.4 ± 14.3 µg/gHb in the obese and controls, respectively (p < 0.05). Regression analysis showed that the body mass index (t =-2.85) and waist circumference (t = -2.37) have a negative relationship only with the erythrocytary zinc (R² = 0.32, p < 0.05). CONCLUSIONS: The study shows that there are alterations in biochemical parameters of zinc in obese women, with low zinc concentrations in erythrocytes. Regression analysis demonstrates that the erythrocytary zinc is influenced by biomarkers of the metabolic syndrome, presenting an inverse relationship with the waist circumference and body mass index.

Basilar artery thrombosis: imaging and endovascular therapy.

PURPOSE: Basilar artery thrombosis represents a rare type of ischaemic stroke with a mortality rate of 80%-90% if not promptly treated. The aim of our study was to review our experience with computed tomography angiography (CTA) in the diagnosis of basilar artery thrombosis and its treatment with endovascular procedures. MATERIALS AND METHODS: Our retrospective study is based upon 59 nontrauma patients with episodes of sudden loss of consciousness. Patients were investigated using unenhanced brain CT followed by intracranial CTA (16-slice CT) when no parenchymal haemorrhage was detected. Patients with a CTA diagnosis of basilar artery thrombosis were considered for endovascular treatment. CTA accuracy was evaluated by considering the 12 patients who underwent endovascular angiography (the gold standard). The success of endovascular therapy was evaluated by considering the degree of microcirculatory reperfusion. RESULTS: After the exclusion of 33 patients affected by parenchymal or subarachnoid haemorrhage, the final study consisted of 26 patients who underwent CTA. Basilar artery thrombosis was diagnosed in 15 of them, and 12 were treated at our institution. The comparison between CTA and endovascular angiography showed 100% agreement in evaluating occlusion site and extension. Seven patients underwent intra-arterial lysis, and five underwent mechanical clot removal. CONCLUSIONS: CTA, with its wide availability and rapid execution times, is the most indicated examination in the case of suspected basilar artery thrombosis. Although there is a lack of randomised controlled prospective studies suggesting the most appropriate therapeutic approach to basilar artery thrombosis, our study lends weight to the role of interventional neuroradiology in the treatment of this condition.

Evaluation of plasma antioxidant levels during different phases of illness in adult patients with bipolar disorder.

The aim of the present study is to evaluate role of plasma antioxidants (albumin, bilirubin and uric acid) in patients suffering from type I Bipolar Disorder (BD-I) during different phases of illness: acute mania, euthymia and bipolar depression. Medical records of consecutive 110 BD-I patients (38 patients with acute mania, 35 in euthymic state, full remission, and 37 in depressive phase) were reviewed to evaluate plasma antioxidant levels. Laboratory data of 40 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. Serum uric acid levels were higher in acute mania than other patient subgroups and healthy controls. Serum uric acid levels directly correlated with BRMRS and YMRS scores. No differences were found between clinical groups during different phases and healthy controls concerning albumin and bilirubin. In conclusion, the results of the present study support the notion that serum uric acid levels may be higher in patients with BP-I (especially during manic phases) which may suggest a dysregulation of the purinergic system. However, limitations should be considered and further studies are needed.

Strategies of endoleak management following endoluminal treatment of abdominal aortic aneurysms in 95 patients: how, when and why.

PURPOSE: This study reviews, on the basis of our experience, the indications and options for treating endoleaks (EL) after endovascular repair of abdominal aortic aneurysms (AAA) by endografting. MATERIALS AND METHODS: Ninety-five patients (M/F =92/3; mean age at time of operation 70.7+/-7.8 years) who underwent endovascular repair of infrarenal AAA between April 1997 and October 2004 were considered. All images of 420 pre-and postoperative computed tomography (CT) studies were reviewed. RESULTS: A total of 37 EL occurred in 33/95 patients (34.7%), four of whom had two EL of different types. Eighteen EL were treated, 16 by endoluminal treatment. Six EL were type I: 2 were treated by percutaneous transluminal angioplasty (PTA) and 4 by cuff deployment (2 proximal cuffs and 2 distal cuffs). Eight EL were type II: 2 were treated by PTA, 2 by cuff deployment, 1 by transcatheter coil embolisation of the inferior mesenteric artery, two by thrombin injection in the aneurysm sac and one underwent surgical conversion during an attempt to treat a concomitant type I EL. Finally, 2 EL were type III: 1 was treated by PTA and 1 by cuff deployment. Endovascular treatment was successful in 12/16 cases (75%), whereas 3/16 cases (18.8%) were converted to open surgery, and 1 patient died of AAA rupture the day after endovascular repair. CONCLUSIONS: EL is the most common complication after endovascular repair of AAA. In type I and type III EL, treatment is mandatory, whereas in type II (and type V) EL, treatment is indicated in the presence of AAA enlargement. Type IV EL generally disappear spontaneously. Endovascular repair is feasible and can be performed with different techniques according to EL aetiology, but it is not always decisive, and in some cases surgical conversion is required.

Evaluation of C-reactive protein and total serum cholesterol in adult patients with bipolar disorder.

The aim of the present study is to evaluate the role of CRP and Total Cholesterol (TC) in patients suffering from type I Bipolar Disorder (BD-I). Moreover, the goal is to elucidate possible CRP and TC differences in different phases of BD-I: acute mania, euthymia and bipolar depression. Medical records of 90 BD-I patients (30 patients with acute mania, 30 in euthymic state, full remission, and 30 in depressive phase) were reviewed to evaluate serum CRP and TC levels. Laboratory data of 30 healthy controls were also obtained. The scores of Young Mania Rating Scale (YMRS), Bech-Rafaelsen Manic Rating Scale (BRMRS) and Hamilton Rating Scale for Depression (HAM-D) were evaluated. CRP levels were higher in acute mania and depressive phase subgroups when compared to healthy controls. CRP was positively associated with BRMRS and YMRS scores in acute mania and with HAM-D in depressive phase subgroups. TC levels were lower in all clinical groups compared to controls. TC levels were negatively correlated to BRMRS, YMRS and HAM-D. In conclusion, the results of the present study support the notion that CRP and TC may be altered in patients with BP-I.

Electrical stimulation and treadmill gait in tetraplegic patients: assessment of its effects on the knee with magnetic resonance imaging.

STUDY DESIGN: Evaluation of knees of tetraplegic patients who have been walking for several months with the aid of a system that involves neuromuscular stimulation, treadmill and a harness support device. OBJECTIVES: To investigate if the training program could cause knee injury to tetraplegic patients. SETTING: Hospital das Clinicas - UNICAMP. Campinas-SP, Brazil. METHODS: Nine patients were evaluated. Clinical exam and magnetic resonance images (MRIs) were used for evaluation. MRIs were taken before and after the training program, in a 6-month interval for each patient. There were two sessions of training every week. Each session lasted 20 min. RESULTS: No severe clinical abnormality was observed in any patient. Mild knee injury was observed in four of nine patients studied. CONCLUSIONS: Tetraplegic patients undergoing treadmill gait training deserve a close follow-up to prevent knee injury.