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Polycythemia is defined as a central venous hematocrit level of more than 65%. Polycythemia occurs because of increased red cell mass, with decreased, normal, or increased plasma volume. On the other hand, hyperviscosity of blood results in increased resistance to blood flow and decreased oxygen delivery. Both polycythemia and hyperviscosity can cause central nervous system dysfunction, hypoglycemia, impaired renal function, and cardiorespiratory distress. Hyperviscosity has also been reported to be associated with long-term neurodevelopmental disorders in childhood. Polycythemia and hyperviscosity are related to alterations in organ perfusion. There is a decrease in end-organ blood perfusion due to changes in red cell mass, arterial oxygen content, and/or viscosity. There are two main treatment approaches to neonatal polycythemia. The first approach is restrictive management, whereas the second approach is partial exchange transfusion, a more controversial one. Partial exchange transfusion is a procedure in which the blood of the infant is diluted. Various studies have had outcomes suggesting no clinically significant short and long-term benefits of the partial exchange transfusion, especially in asymptomatic infants and infants with minor symptoms. However, it is crucial to note that there are no long-term follow-up studies to evaluate the neurodevelopmental status of infants with neonatal polycythemia. In contrast to partial exchange transfusion, restrictive management has been confronted with several difficulties. Therefore, further controlled studies with new methods are needed to observe the long-term effects. In this review, it is aimed to evaluate the efficacy of current and recently retrieved treatment approaches in neonatal polycythemia. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a blood cell neoplasm characterized by excessive production of malignant monoclonal plasma cells (activated B lymphocytes) by the bone marrow, which end up synthesizing antibodies or antibody fragments, called M proteins, in excess. The accumulation of this production, both cells themselves and of the immunoglobulins, causes a series of problems for the patient, of a systemic and local nature, such as blood hyperviscosity, renal failure, anemia, bone lesions, and infections due to compromised immunity. MM is the third most common hematological neoplasm, constituting 1% of all cancer cases, and is a disease that is difficult to treat, still being considered an incurable disease. The treatments currently available cannot cure the patient, but only extend their lifespan, and the main and most effective alternative is autologous hematopoietic stem cell transplantation, but not every patient is eligible, often due to age and pre-existing comorbidities. In this context, the search for new therapies that can bring better results to patients is of utmost importance. Protein tyrosine kinases (PTKs) are involved in several biological processes, such as cell growth regulation and proliferation, thus, mutations that affect their functionality can have a great impact on crucial molecular pathways in the cells, leading to tumorigenesis. In the past couple of decades, the use of small-molecule inhibitors, which include tyrosine kinase inhibitors (TKIs), has been a hallmark in the treatment of hematological malignancies, and MM patients may also benefit from TKI-based treatment strategies. In this review, we seek to understand the applicability of TKIs used in MM clinical trials in the last 10 years. [ABSTRACT FROM AUTHOR]

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by measuring cell viability using two tests (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment had a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of five (RO5), which increases their chances for possible use as orally active drugs with good absorption ability and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethylamino)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential. [ABSTRACT FROM AUTHOR]

Adenomyosis is an estrogen‑dependent gynecologic disease characterized by the presence of endometrial tissue within the myometrium. Adenomyosis presents with abnormal uterine bleeding, pelvic pain and infertility. Recently, patients with adenomyosis with life‑threatening disseminated intravas‑ cular coagulation (DIC) or thromboembolic events have been reported. The purpose of the present systematic review was to examine the possible associations between adenomyosis and severe complications, and to investigate the clinical characteristics, risk factors and potential mechanisms. A literature search was performed for case reports, reviews of the literature, and preclinical and clinical studies published between January, 2000 and November, 2021 in the PubMed and Google Scholar databases using a combination of specific terms. A total of 20 articles reported these complications. Adenomyosis is characterized by morphologically and func‑ tionally abnormal blood vessels, with increased intramural pressure, increased expression of pro‑angiogenic markers, excessive angiogenesis and increased microvascular density. Changes in blood coagulation‑fibrinolysis markers are encountered even in asymptomatic women during menstrua‑ tion. Repeated bleeding in larger lesions causes coagulopathy that may result in localized thrombosis or DIC. In addition, elevated levels of mucinous tumor markers, CA125 and CA19‑9, induce blood hyperviscosity and hypercoagulability that predispose patients to thromboembolism. On the whole, as demonstrated herein, adenomyosis may cause a wide range of symptoms from asymptomatic to life‑threatening DIC and/or thromboembolism. [ABSTRACT FROM AUTHOR]

BACKGROUND: Elevated estimated blood viscosity (EBV), derived from hematocrit and globulins, is associated with thrombotic complications, organ failure, and higher mortality in COVID-19 patients. Although informative, EBV does not account for cellular interactions or fibrinogen. OBJECTIVE: Investigate whether patients with acute and recent COVID-19 have altered whole blood viscosity (WBV) when measured at both high and low shear rates using in vitro blood samples from patients. METHODS: Cross-sectional study of 58 patients: 15 in the intensive care unit with acute COVID-19, 32 convalescent (9 < 8weeks [W] from acute infection, 23 > 8 W), and 11 controls without COVID-19. WBV was measured at high (300 s–1) and low (5 s–1) shear rates (HSR, LSR) using a scanning capillary viscometer. RESULTS: Acute and convalescent patients < 8 W had mean WBV at LSR (16.0 centipoise [cP] and 15.1 cP) and HSR (5.1 cP and 4.7 cP). Mean WBV of convalescent > 8 W and control patients were 12.3 cP and 13.0 cP at LSR, and 4.1 cP and 4.2 cP at HSR. Acute and < 8 W patients had significantly higher WBV at both HSR and LSR compared to patients > 8 W (all p≤0.01). No significant differences in WBV were observed between acute and < 8 W patients, or between patients > 8 W and controls. CONCLUSIONS: Hyperviscosity provides a possible explanation for thrombotic risk in acute and convalescent (< 8 W) patients. These findings have important implications for thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Background: Waldenstrom macroglobulinemia (WM) is a rare lymphoma with an incidence rate of 3 per million people per year, with approximately 1000 to 1500 new cases diagnosed each year in the USA. It is primarily seen in Caucasian males with a median age of 70 years old. Patients are most often asymptomatic, but WM can manifest itself with constitutional symptoms such as lethargy, bleeding, organomegaly, and neurological or fundoscopic abnormalities. WM is characterized by immunoglobulin M (IgM) monoclonal gammopathy, lymphocytic infiltration of bone marrow, and normocytic anemia due to bone marrow replacement. Case presentation: Our patient is a Hispanic 67-year-old female that presents with one month of intermittent band-like bilateral headache accompanied by dizziness, light-headedness, nausea, and blurred vision. A thorough diagnostic workup was performed, including serum protein electrophoresis (SPEP) with serum immunofixation (SIFE) showing an M spike and IgM kappa. Bone marrow biopsy was significant for lymphoplasmacytic infiltration with nodular B cells (CD19+, CD20+, CD22+). Computerized Tomography (CT) imaging showed splenomegaly in the patient. Treatment was provided for hyperviscosity syndrome with plasmapheresis twice. The patient reported improvement of her symptoms and was then scheduled for chemotherapy. Throughout 7 months, our patient received multiple cycles of bortezomib, dexamethasone, and rituximab. While her symptoms improved her psychiatric status got progressively worse. Conclusion: It is important not to neglect symptoms such as a headache, which may seem small, but could serve as a clue in the diagnosis of Waldenstrom's macroglobulinemia. [ABSTRACT FROM AUTHOR]

Polycythemia vera (PV) is a chronic myeloproliferative neoplasm resulting in increased red blood cell mass. It can lead to various symptoms caused by blood hyperviscosity and an elevated number of red blood cells. Both thrombosis and bleeding complications can occur in PV. Splenic infarction is a rare complication with an unknown incidence usually presenting with pain in the upper left quadrant of the abdomen. The treatment is usually conservative, but there are some complications requiring surgery. We describe an elderly female patient who presented to the emergency department with left costal margin pain which was caused by splenic infarction. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Tepecik Education & Research Hospital / İzmir Tepecik Eğitim ve Araştırma Hastanesi Dergisi is the property of Logos Medical Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Polycythemia vera is a myeloproliferative disorder caused by clonal expansion of erythroid precursors in the bone marrow commonly due to a mutation in the Janus kinase 2 (JAK2) gene located in the short arm of chromosome 9. Hyperviscosity of blood due to high hematocrit causes a low flow state that may predispose to infarct. These commonly occur in the supratentorial compartment. The case of a 46-year-old man who had an isolated cerebellar infarct with high hematocrit and hemoglobin levels and low serum erythropoietin levels is described. Further investigations eventually led to the unmasking of a JAK2 mutation-negative polycythemia vera. [ABSTRACT FROM AUTHOR]

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Objective: The objectives of this study were to: 1) characterize the distribution of noninterfering pain (defined as the pain intensity level at which individuals can function without interference) across different aspects of life among patients with rheumatoid arthritis (RA), and 2) identify clinical characteristics associated with differing levels of noninterfering pain.Methods: Patients with RA in FORWARD, The National Databank for Rheumatic Diseases completed 8 items from the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference item bank that asked about interference with activities. If subjects reported pain interference, they were asked, "At what level would pain no longer interfere with this activity?" on a scale of 0 to 10. Subjects were also asked, "At what level of pain would you be able to do everything you want to do?" Multiple linear regression analyses examined associations between clinical characteristics and noninterfering pain.Results: A total of 3,949 patients with RA completed the questionnaires. Pain interference was most common for daily activities and least common for ability to concentrate. The mean ± SD level at which pain no longer interfered with activities ranged from 2.7 ± 2.1 for ability to fall/stay asleep to 3.1 ± 2.0 for social activities. Overall, the mean ± SD threshold for noninterfering pain was 2.8 ± 1.9. The mean ± SD level of pain at which patients could do everything they wanted to do was 2.3 ± 1.9. More severe pain intensity was associated with higher noninterfering pain.Conclusion: The mean pain level that did not interfere with activities was 3. High pain intensity was associated with high self-reported noninterfering pain. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 69-year-old woman with the history of IgG monoclonal gammopathy of undetermined significance (MGUS), hypertension, idiopathic pulmonary fibrosis, and chronic kidney disease. Topics include showing the concern for hypergammaglobulinemia-induced hyperviscosity syndrome (HVS) and persistent coagulopathy; and Serum immunotyping confirming the presence of an IgG lambda monoclonal protein.

Background: Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID‐19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID‐19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID‐19‐associated hyperviscosity. Study Design and Methods: Six critically ill COVID‐19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4‐1.8 cP) underwent daily TPE for 2‐3 treatments. Results: TPE decreased plasma viscosity in all six patients (Pre‐TPE median 3.75 cP, range 2.6‐4.2 cP; Post‐TPE median 1.6 cP, range 1.5‐1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre‐TPE median 739 mg/dL, range 601‐1188 mg/dL; Post‐TPE median 359 mg/dL, range 235‐461 mg/dL); D‐dimer levels in all six patients (Pre‐TPE median 5921 ng/mL, range 1134‐60 000 ng/mL; Post‐TPE median 4893 ng/mL, range 620‐7518 ng/mL); and CRP levels in five of six patients (Pre‐TPE median 292 mg/L, range 136‐329 mg/L; Post‐TPE median 84 mg/L, range 31‐211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. Conclusions: This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID‐19‐associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID‐19. [ABSTRACT FROM AUTHOR]

This article discusses the cutaneous localization of Waldenström's macroglobulinemia (WM), a rare lymphoproliferative disease. Cutaneous manifestations of WM are rare, occurring in only 5% of patients, and can be neoplastic or non-neoplastic. The neoplastic type presents as firm, erythematopurple papulo-nodules, while the non-infiltrated lesions are brownish macules. The article emphasizes that treatment for cutaneous localizations of WM is only necessary in cases of aesthetic or functional damage, as these localizations do not affect the course of the disease. The article includes a case study of a patient with cutaneous nodules and discusses the diagnostic process. [Extracted from the article]

We developed a model of blood hyperviscosity avoiding extreme impact on the blood. The model shows reproducibility in rat blood under common storage conditions (4±1°C; stabilization with citrate-phosphate-glucose additive solution). Storage of rat blood under these condition leads to impairment of its rheological properties, which manifested in an increase in blood viscosity in a wide range of shear rates (3-300 sec—1). An increase in blood viscosity appeared the first day of storage and reached a maximum on the third day. During further 11-day storage, the blood viscosity did not change significantly. A hybrid macromolecular compound O-(3-(3,5-di-tert-butyl-4-hydroxyphenyl)propanoyl)-(1→6)-α-D-glucan improved the hemorheological properties during storage. The most pronounced effect was observed on the third day of storage and manifested in a decrease in blood viscosity in the range of shear rates of 50-300 sec—1. Thus, storage of rat blood with citrate-phosphate-glucose additive solution for 3 days at 4±1°C reproduces the phenomenon of blood hyperviscosity; this model can be used to screen agents with hemorheological activity. [ABSTRACT FROM AUTHOR]

Priapism is a rare urological emergency. It is rarely a telltale sign of myeloid leukemia. We report two cases of acute myeloid leukemia in a child and chronic myeloid leukemia in a young adult presenting with priapism. Puncture irrigation of the corpora cavernosa followed by systemic treatment to lower the hyperviscosity of the blood due to leukemia provided optimal outcome. Prompt emergency management is required to lower the complication of erectile dysfunction. [ABSTRACT FROM AUTHOR]

Background: Plasma viscosity is an important biomarker both in diagnostics and treatment monitoring of plasma cell dyscrasias and other disorders with hyperviscosity syndrome as a clinical manifestation. Here, we investigate the performance of a new microfluidic-based viscometer for clinical use, establish a new reference range to be used with this instrument and determine the importance of sampling temperature.Methods: The microVisc™ viscometer was evaluated for within-run and between-run imprecision and bias using standardized reference material (Paragon controls) and Seronorm™ control material. The reference range was established for the adult population using EDTA-plasma from 120 healthy blood donors. Sampling temperature was investigated by drawing and transporting blood at room temperature and 37°C and comparing the viscosity between the two sampling methods.Results: The microfluidic-based viscometer performed well, and imprecision was comparable to ReoRox® G2 free oscillation rheometer. A new reference range for the adult Danish population was established as 1.2-1.5 mPa s at 37°C. Furthermore, sampling temperature at room temperature and 37°C was investigated, and there was no difference in results obtained.Conclusions: MicroVisc™ is suitable for measuring plasma viscosity in a clinical setting and results can be evaluated using the established reference range. Blood sampling for viscosity analysis can be performed as a standard procedure at room temperature. [ABSTRACT FROM AUTHOR]

The article presents a case of an 81-year-old woman who was rushed to the hospital due to coronary angiography and viscous blood. She had a history of Lyme disease, hypothyroidism, gastroesophageal reflux disease, hyperlipidemia, and moderate coronary artery disease. She was given a differential diagnosis of hyperviscosity syndrome and Waldenstrom macroglobulinemia (WM). She underwent therapeutic plasma exchange (TPE) and treated with Rituximab.

Aims: To investigate the relative importance of systemic and local inflammatory mediators (serotonin: 5-HT; tumor necrosis factor: TNF; soluble interleukin-1 receptor II: IL-1sRII) in the modulation of temporomandibular joint (TMJ) pressure pain threshold in patients with seropositive or seronegative rheumatoid arthritis (RA) and to investigate to what extent TMJ pressure pain threshold is related to other TMJ pain parameters. Methods: Sixty patients with seropositive RA for rheumatoid factor and 74 patients with seronegative RA involving the TMJ were investigated regarding synovial fluid and plasma levels of IL-1sRII, 5-HT, and TNF as well as erythrocyte sedimentation rate, C-reactive protein, thrombocyte particle count, and rheumatoid factor in blood. TMJ resting pain, movement pain, tenderness, and palpebral pain reflex to digital palpation and TMJ pressure pain threshold were examined. Results: Statistical analyses indicated that TMJ pressure pain threshold was only correlated to systemic factors. TMJ movement pain was in turn mainly correlated to systemic mediators in the seropositive patients but to local mediators in the seronegative patients where synovial fluid IL-1sRII was positively correlated to TMJ pain on mouth opening. Seropositive patients had higher systemic inflammatory activity but lower TMJ movement pain intensities than seronegative patients. Conclusion: The results indicate that TMJ pressure pain threshold is modulated by systemic rather than local inflammatory mediators and suggest that it is unrelated or only weakly related to other TMJ pain entities in RA patients. A rheumatoid factor-dependent systemic modulation, in combination with local factors, seems to account for TMJ pain in RA patients. [ABSTRACT FROM AUTHOR]

Introduction: In Unani system of medicine, blood is regarded as mixture of akhlat (humours) i.e. dam (Sanguine), balgham (phlegm), safra (yellow bile) and sawda (black bile). Normal blood consists of "akhlate latifa (plasma)" and "kaseefa (corpuscles)". Normal blood is one in which all humours are in normal proportion in terms of quantity and quality and specific to each individual. It is normal in colour, free from bad odour and moderate in viscosity. Morbid blood develops due to impurities /disease in the blood which ultimately alter its quantity and quality. If we co relate these abnormalities with modern concept then all bleeding disorders and coagulopathy fall under "Riqqate dam" (low viscosity of blood); all the thromboembolic disorders; polycythaemia, leukaemia and anaemia fall under "Ghilzate dam"(hyperviscosity of blood), while septicaemia, bacterial diseases can be correlated with "ufunat" (infections). Methods: The classic and relevant books of Unani and conventional medicine were studied. The databases utilized for obtaining information, are scientific research publications from indexed journals available through Google Scholar, PubMed and Science Direct. Results and Conclusion: Blood purifying drugs cause necessary changes and maintain the viscosity of the blood by their moderate heat; cold; dry and wet properties. These drugs are alterative and bring the quality and quantity of blood in equilibrium. Strengthen the defensive mechanism and eliminate toxins via sweat, urine, faeces etc. These drugs are digestive, tonic to stomach and liver and boost the immune system. In the line of the above conceptual framework few experimental models are being suggested i.e. effect of drugs on blood constituents, coagulation parameters, anemia, leukaemia, polycythaemia, thrombocytopenia and infections. This preliminary study may serve as a tool for the screening of blood purifier drugs in various blood disorders. [ABSTRACT FROM AUTHOR]

The article presents a guideline for diagnosis as well as management of polycythaemia vera. Review of the manuscript was conducted by British Society for Haematology's Guidelines Committee General Haematology Task Force. According to the guideline, several renal and hepatic diseases may result in erythrocytosis.

The article presents a guideline from British Society for Haematology for management of particular conditions in case of polycythaemia vera and secondary erythrocytosis. The guideline evaluates the evidence and outline guidance related to management of acute thrombotic events as well as secondary prevention of thrombosis in polycythaemia vera.

Background/aim: We aimed to assess the association between retinal vascular caliber (RVC) scores and disease activity in rheumatoid arthritis (RA) patients. Materials and methods: Forty-seven RA patients, 32 systemic lupus erythematosus (SLE) patients, and 45 healthy people were enrolled. RA and SLE patients were subdivided into groups according to C-reactive protein (CRP) levels. RA patients were also grouped according to Disease Activity Score-28 (DAS-28). Fundus photography was performed for all patients. RVC was summarized as the central retinal artery and vein equivalents (CRAE and CRVE). Results: Mean CRVE for RA patients was 213.3 ± 17.8 µm compared with 209.2 ± 14.1 µm for SLE and 217.5 ± 26.2 µm for the control group (P = 0.17). RVC scores did not differ between the CRP-high and CRP-low groups. As the RA disease activity increased, the widening of CRVE became more prominent and statistically significant. When the DAS-28 > 5.1 (CRVE, 220.4 (211.8-246.5) µm) group and DAS-28 = 3.2 (CRVE, 214.4 (172.4-242.3) µm) group were compared, statistical significance was more pronounced (P = 0.03) than when comparing the DAS-28 > 3.2 and DAS-28 = 3.2 groups (P = 0.05). Conclusion: CRVE, which reflects systemic inflammation and possibly increased cardiovascular risk, was significantly increased in active RA patients. The association between retinal venular widening and disease activity, regardless of CRP, may be a sign that RArelated inflammation may have systemic vascular effects even with normal levels of CRP. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Craniomandibular Disorders is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Orofacial Pain is the property of Quintessence Publishing Company Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Takotsubo cardiomyopathy (TTS) has long been considered a benign condition, despite recurrent events and long-term adverse outcomes are often reported. Endothelial damage, blood hyperviscosity, and platelet activation described in acute phase persist in long-term follow-up; however, TTS pathophysiology is still not fully understood. Here, we explored the hemostatic system at a median of 3.1 years after TTS to uncover additional long-lasting changes in these patients. We assessed hemostatic parameters in women with TTS (n = 23) or coronary artery disease (CAD; n = 31) and in control women (n = 26) age-matched, by thromboelastographic analysis, prothrombin time (PT) and partial thromboplastin time (aPTT) coagulation assays and microparticle exposing Tissue Factor (MP-TF). Functional fibrinogen and fibrin polymerization were analyzed by Clauss method and spectrophotometry, respectively. Platelet reactivity was evaluated by light transmission aggregometry, whereas plasminogen activator inhibitor-1 (PAI-1) and brain-derived neurotrophic factor (BDNF) were measured by ELISA kit. Compared with control subjects, TTS patients exhibit an accelerated clot formation, higher percentage of fibrin polymerization and higher PAI-1 levels. Compared with CAD, TTS patients showed sustained residual platelet activation but decreased functional fibrinogen, fibrin polymerization and MP-TF levels, prolonged aPTT and a marked BDNF increase. The long-term activation of hemostatic system observed in TTS patients compared to control subjects suggests a persistent humoral abnormality that may be related to the propensity for TTS recurrence. The higher residual platelet activity observed in TTS than in CAD patients invites investigation on TTS-tailored antiplatelet therapy potentially needed to prevent TTS adverse outcomes. • Takotsubo syndrome has been recently indicated as a life-threatening condition. • Takotsubo patients exhibit hemostatic activation compared to control subjects. • Takotsubo patients show a residual platelet activation compared to CAD patients. [ABSTRACT FROM AUTHOR]

Tetrology of Fallot's (TOF) is the most common cause of cyanotic congenital heart disease, and accounts for 10% of all congenital heart diseases. Right to left shunting and hyperviscosity of blood predisposes these patients to brain abscess. Perioperative management of these patients with uncorrected TOF for noncardiac surgery is a challenge for the anesthesiologists owing to the long-term effects of hypoxia and decreased pulmonary blood flow, resulting in considerable modification of the physiology and neurological complications. We are hereby reporting the anaesthetic management of an 8 year old child with uncorrected TOF presenting with multiple brain abscesses who underwent craniotomy with uneventful recovery. [ABSTRACT FROM AUTHOR]

To assess the role of musculoskeletal ultrasound as a predictor for the achievement of DAS28 remission in patients with rheumatoid arthritis (RA). One hundred and forty-one patients underwent physical and ultrasound examination at five visits (at baseline and after 1, 3, 6 and 12 months). Patients were divided into two groups according to the type of treatment, which involved synthetic (sDMARDs) and biologic (bDMARDs) disease-modifying antirheumatic drugs. Ultrasound assessment of the wrist, second and third metacarpophalangeal, second and third proximal interphalangeal joint, second and fifth metatarsophalangeal joint (the German US7 score) was performed on gray scale (GS) and on power Doppler ultrasound (PDUS). The rate of clinical remission and clinical and sonographic predictors for the achievement of DAS28 remission at month 12 were assessed. In the sDMARDs group at month 12, 43.6% of the patients achieved DAS28 remission, 5.1%—SDAI, 3.8%—CDAI, and 3.8%—Boolean remission. In the bDMARDs group, 49.2% achieved DAS28 remission, 6.3%—SDAI, 4.8%—CDAI, and 4.8%—Boolean remission. Predictors for DAS28 clinical remission in the sDMARDs group were low baseline DAS28 (p = 0.002), short disease duration (p = 0.007) and lower baseline PDUS score (p = 0.038). In the bDMARDs group low baseline DAS28 (p < 0.001) and PDUS score (p = 0.035) predicted DAS28 remission. Shorter disease duration, lower baseline DAS28 and PDUS scores are associated with a higher probability of achieving DAS28 remission at month 12 in patients with RA. Musculoskeletal ultrasound and in particular the German US7-scoring system may be used as a predictor for the achievement of clinical remission in RA patients. [ABSTRACT FROM AUTHOR]

To determine the contribution of fibromyalgia (FM) to the subjective components of the Disease Activity Score 28-joints (DAS28) in patients with rheumatoid arthritis (RA), and to analyse the discriminatory performance of the derived DAS28 patient-reported components (DAS28-P) to identify patients with fibromyalgic RA. Consecutive RA patients underwent clinical and clinimetric assessment. The DAS28-P index was derived from the components of the DAS28 scores by rearranging the DAS28-ESR formula. Patients were distinguished by the presence of FM. Student parametric t tests or Mann-Whitney non-parametric U tests were used to determine any between-group differences. Receiver operating characteristic (ROC) curve analysis was used to test the ability of the DAS28-P index to distinguish patients with RA and those with fibromyalgic RA. The study involved 292 RA patients (80.5% females, mean age 63 years) with a mean disease duration of 11.6 ± 8.5 years. Forty-three patients (14.7%) had concomitant FM, and significantly higher tender joint count (p < 0.001), pain numerical rating scale, global health status (p = 0.007), and DAS28 scores (p = 0.006) than those without FM. The DAS28-P values were also significantly higher in the patients with FM (0.68 ± 0.09 vs 0.58 ± 0.06; p < 0.001). The discriminatory power of the DAS28-P was very good (area under the ROC of 0.858, optimal cut-off value of 0.631). The presence of FM strongly influences the DAS28 results. The assessment of patient-reported components to the DAS28 through the DAS28-P can be a useful way to identify patients with fibromyalgic RA. [ABSTRACT FROM AUTHOR]

The utility of superb microvascular imaging (SMI) for evaluating hand joint lesions in patients with rheumatoid arthritis (RA) in clinical remission is unreported. This study aimed to compare SMI and power Doppler imaging (PDI) for the evaluation of hand joint lesions in these patients. Twenty-six patients with RA in clinical remission were enrolled. A total of 572 joints (52 wrist, 260 proximal interphalangeal, and 260 metacarpophalangeal joints) were detected by SMI and PDI. A semi-quantitative scale of 0-3 was used to compare the detection of synovial blood flow signal by SMI and PDI. Inter-observer agreement for the assessment of SMI and PDI scores was measured with kappa values. In the ten healthy volunteers, SMI and PDI signals were both scored 0. In the 26 RA patients, the remission rate via PDI was 65.4% but was only 42.3% via SMI. SMI also detected microvessel flow signal in seven patients diagnosed with clinical remission via PDI. Moreover, a total of 106 blood flow signals (18.5%) were detected by SMI, while 50 blood flow signals (8.7%) were detected by PDI. Compared with PDI, SMI increased 18.0% of power flow signals from Grade 0-1 and increased 13.7% of power flow signals from Grade 1-2. One joint classified as Grade 1 by PDI was classified as Grade 0 by SMI. Inter-observer agreement for PDI and SMI semi-quantitative scoring was moderate (kappa = 0.463). SMI seems more sensitive than PDI for detecting hand joint lesions in RA in clinical remission PDI, and could aid the achievement of true remission in RA patients. [ABSTRACT FROM AUTHOR]

Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an elevation in the serum viscosity do not require plasma exchange, and the majority will have other indications for therapeutic intervention. For patients with hemorrhagic or central nervous system manifestations, plasma exchange is the therapy of choice and is relatively safe. Viscosity measurements are not required to initiate therapy if the index of suspicion is high and the clinical presentation is typical. However, patients should have a sample sent for confirmation of the diagnosis. Whole-blood hyperviscosity is seen in patients with extreme elevation of the red cell and white cell count. Phlebotomy of patients with primary and secondary elevation of the red cell count is a wellestablished therapy. [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized with joint destructions; environmental and genetic factors were thought to be involved in the etiology of RA. The production of anti-citrullinated peptide antibodies (ACPA) is specifically associated with RA. DRB1 is associated with the susceptibility of RA, especially ACPA-positive RA [ACPA(+)RA]. However, a few studies reported on the independent associations of DPB1 alleles with RA susceptibility. Thus, we investigated the independent association of DPB1 alleles with RA in Japanese populations. Methods: Association analyses of DPB1 were conducted by logistic regression analysis in 1667 RA patients and 413 controls. Results: In unconditioned analysis, DPB1*04:02 was nominally associated with the susceptibility of ACPA(+)RA (P = 0.0021, corrected P (Pc) = 0.0275, odds ratio [OR] 1.52, 95% confidence interval [CI] 1.16–1.99). A significant association of DPB1*02:01 with the susceptibility of ACPA(+)RA was observed, when conditioned on DRB1 (Padjusted = 0.0003, Pcadjusted = 0.0040, ORadjusted 1.47, 95%CI 1.19–1.81). DPB1*05:01 was tended to be associated with the protection against ACPA(+)RA, when conditioned on DRB1 (Padjusted = 0.0091, Pcadjusted = 0.1184, ORadjusted 0.78, 95%CI 0.65–0.94). When conditioned on DRB1, the association of DPB1*04:02 with ACPA(+)RA was disappeared. No association of DPB1 alleles with ACPA-negative RA was detected. Conclusion: The independent association of DPB1*02:01 with Japanese ACPA(+)RA was identified. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although hyperviscosity syndrome in plasma cell dyscrasia (PCD) and thrombosis in myeloproliferative neoplasm (MPN) are major causes of morbidity and mortality, blood viscosity measurements are often underutilized. OBJECTIVE: This study aimed to characterize whether whole blood viscosity (WBV) or plasma viscosity (PV) could be predictive of hyperviscosity syndrome in PCD and could be elevated in subgroups of MPN. METHODS: A total of 75 patients with hematologic diseases: PCD (n = 26), MPN (n = 25) including polycythemia vera (P. vera) and lymphoma (n = 24) were enrolled along with 104 healthy controls. Both WBV and PV were measured using a capillary tube viscometer. Hyperviscosity syndrome was defined as having 2 or more hyperviscosity symptoms. RESULTS: Patients with PCD showed significantly higher PVs at high and low shear rates when compared to healthy controls, especially in those with hyperviscosity syndrome. The sensitivity and specificity of WBV and PV in detecting hyperviscosity syndrome were 28.6% and 94.1%, and 71.4% and 66.7%, respectively. Patients with P. vera exhibited high WBV and RBC counts compared to healthy controls. CONCLUSION: PV is predictive of hyperviscosity syndrome in PCD and WBV is elevated in patients with P. vera. It suggests that hemorheologic disturbances exist in patients with PCD and MPN and that tests of viscosity may be helpful in detecting hemorheological disturbances. [ABSTRACT FROM AUTHOR]

The coronary artery calcification (CAC) progression may be useful noninvasive predictor of future cardiovascular events (CVE). The progression rate of CAC in patients with early rheumatoid arthritis (RA) is poorly understood. To assess the dynamic of CAC scores in early RA patients for 18 months, 74 RA adult patients (ACR/EULAR criteria, 2010, duration ≤ 12 months, with moderate/high RA activity, without prior administration of disease-modifying anti-rheumatic drugs or glucocorticoids) were enrolled within the framework of the observational study: women 73%, median age 56 years, median RA duration 6 months, median DAS28[ESR] 5.4. Most of the patients had multiple Traditional Risk Factors (TRFs) of Cardiovascular Disease (CVD). All patients at baseline and after 18 months underwent 32-row scanning for CAC scoring. In patients younger than 45 years (n = 16) any CAC was not detected during 18 months. Among patients older than 45 years four new events of CAC were detected. Among patients older than 45 years with baseline CAC (n = 34) increase in CAC scores was detected in 82% cases. Among them, Δ Agatston Score exceeded the median annual Agatston Score progression predicted for the general population according to the Multi-Ethnic Study of Atherosclerosis (MESA) data in 57% of early RA patients. The significant increase of Agatston Score in accordance with Sevrukov’s method was met in one patient with newly diagnosed CAC and among patients with baseline CAC—in 29%. The presence of CAC progression was associated with lower baseline total cholesterol (TC) level (p < 0.05). The extent of CAC progression associated with male gender and arterial hypertension (AH) (p < 0.05). Association between CAC dynamic and statin therapy, RA activity and cumulative inflammatory burden, response to anti-rheumatic therapy and the type of this therapy were not detected. Early RA patients older than 45 years have high incidence of CAC progression during 18 months. More than half of the early RA patients had the increase in AS which exceeded the median annual progression of Agatston Score in the MESA. The CAC progression was associated with male gender, AH and lower baseline TC level. We did not detect any association between CAC progression and statin therapy, RA activity and type of anti-rheumatic therapy. [ABSTRACT FROM AUTHOR]

Problem: Sexually transmitted diseases and other infections of male genitourinary tract are thought to negatively impact reproductive health, affecting semen quality. Despite a possible link between bacteria and infertility, few studies attempted to characterize seminal microbiota in healthy and diseased subjects. Methods of the study: A high‐throughput sequencing of 16S ribosomal RNA gene was performed in a cohort of infertility‐related cases (N = 89) and controls (N = 29) using a pooled sample approach. Results: A global characterization of microbiota was obtained at low cost, without compromising the identification of bacterial taxa. This strategy allowed us to detect changes in the microbiota of infertility‐related phenotypes, such as an increment of Proteobacteria in seminal hyperviscosity, and to separate this later group from oligoasthenoteratozoospermia based in bacterial (family/genus) abundances. Conclusion: We provide data for a likely contribution of bacteria into seminal hyperviscosity and oligoasthenoteratozoospermia, partially correlated with an increment of Neisseria, Klebsiella, and Pseudomonas pathogens and a reduction in Lactobacillus probiotic agent. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA).Method: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors.Results: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health.Conclusion: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern. [ABSTRACT FROM AUTHOR]

Aim. Examine the efficacy of once-weekly subcutaneous tocilizumab (SC-TCZ) on joint damage at 24 weeks based on radiography of the hands and feet and magnetic resonance imaging (MRI) of the hand in subjects with moderate to severe rheumatoid arthritis (RA). Methods. In this Australian open-label, multicentre, prospective, single-arm study, subjects received 162 mg SC-TCZ weekly. Primary endpoint was change in radiographic Genant-modified Total Sharp Score (TSS) between baseline and Week 24. Secondary endpoints included change from baseline to Week 24 in RA MRI scoring (RAMRIS) of erosions, synovitis, and osteitis and Cartilage Loss Score (CARLOS) in the dominant hand and disease activity score 28 (DAS28). Results. 52 subjects were enrolled (80% female, mean (SD) age 57  (12) years). Radiography showed mild but not significant progression of joint damage (mean (SD) change in TSS 0.46 (1.29)). Synovitis reduced significantly on MRI; however, osteitis, erosion, and cartilage loss did not change significantly. DAS28 improved significantly by Week 24; 78% of subjects achieved DAS28 remission. SC-TCZ was generally well tolerated. Conclusion. Synovitis and DAS28 decreased significantly; however, no significant change in osteitis or joint damage was observed at Week 24. Trial registration. This trial is registered with Clinicaltrials.gov registration number NCT01951170 (ML28703). [ABSTRACT FROM AUTHOR]

The article presents a case study of a 6-year-old boy presented to the Emergency Department after a fall from a bicycle with loss of consciousness. It mentions that Molecular testing for von Hippel-Lindau (VHL) gene mutations revealed the presence of two previously reported mutations confirmed the diagnosis of Chuvash polycythaemia in this child. It further offers information about Chuvash polycythaemia, a rare autosomal recessive congenital polycythaemia.

Abstract: Aim: The purpose of this study was to assess 5‐year changes in physical function and factors associated with improvement among patients with rheumatoid arthritis (RA) in daily clinical practice, focusing on the effect of treatments, including biologic agents, in the early stage of disease course. Methods: The National Database of Rheumatic Diseases by iR‐net in Japan (NinJa) was searched for patients with disease duration ≤ 2 years and modified health assessment questionnaire (mHAQ) > 0 between 2004 and 2007, so that 510 patients were included in the final analysis. Multivariate‐logistic regression analyses were used to identify predictors of 5‐year mHAQ disability score improvement. Results: Median mHAQ score was 0.40 at baseline and decreased to a median 0.17 after 5 years. Seventy‐four percent of the patients were treated with methotrexate (MTX) and 25% with biologic agents, with early use of biologic agents (within 2 years of RA onset) increasing over time. Multivariate analyses identified higher baseline Disease Activity Score of 28 joints – C‐reactive protein and early use of MTX (within 1 year of RA onset) and of biologic agents (within 2 years) as significantly associated with improved mHAQ; odds ratios of the early treatment were 1.83 (P = 0.01) for MTX and 2.23 (P = 0.04) for biologic agents, respectively. Conclusion: Five‐year mHAQ improved in early RA patients in the NinJa database. In daily clinical management of RA, likewise in clinical trials, early administration of MTX or biologic agents is able to improve physical function outcome. [ABSTRACT FROM AUTHOR]

Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing anti-citrullinated peptide antibodies (ACPA) positive and ACPA negative RA. The present report is based on a Swedish population-based, case-control study with incident cases of RA (3655 cases, 5883 matched controls). Using logistic regression models, subjects with different smoking habits were compared regarding risk of developing the two variants of RA, by calculating odds ratios (OR) with 95% confidence intervals (CI). Smoking increased the risk of developing both ACPA positive (OR 1.9, 95% CI 1.7-2.1) and ACPA negative RA (OR 1.3, 95% CI 1.2-1.5). For both subsets of RA, there seemed to be a threshold (~ 2.5 pack years for ACPA positive RA and ~ 5 pack years for ACPA negative RA) below which no association between smoking and RA occurred. A dose-response association was observed between cumulative dose of smoking and risk of developing ACPA positive RA (p value for trend < 0.0001). Duration of smoking had a higher influence on the association between smoking and RA than did intensity of smoking. For both subsets of RA, the detrimental effect of smoking decreased after smoking cessation. Twenty years after smoking cessation, there was no longer an association between smoking and risk of ACPA negative RA, whereas the association between smoking and ACPA positive RA risk persisted and was dependent on the cumulative dose of smoking. Smoking increases the risk of both subsets of RA with a more pronounced influence on the risk of ACPA positive RA. Preventive measures in order to reduce smoking are essential and may result in a decline in RA incidence. [ABSTRACT FROM AUTHOR]

Specific and sensitive detection method for anti-cyclic citrullinated peptide antibody (anti-CCP) is highly in demand for the early diagnosis of rheumatoid arthritis (RA). In this work, a label-free electrogenerated chemiluminescence (ECL) immunosensor for the detection of anti-CCP was proposed based on the application of an interfacially synthesized asymmetric heterogeneous nanomaterial. Dumbbell-like polyaniline-gold (PANI-Au) nanocomposite show excellent synergetic enhancement effect on the ECL behaviors of graphite-like carbon nitride (g-C 3 N 4 ). The formation of electrostatic complex between g-C 3 N 4 and PANI-Au composite improves the interfacial stability of hydrophilic g-C 3 N 4. The synergetic enhancement effect of PANI and Au NPs was confirmed by tailoring the morphology of the nanocomposite. An ECL immunosensor was constructed using asymmetric PANI-Au incorporated g-C 3 N 4 as a sensing platform. The presence of Au NPs enables the facile immobilization of the recognition element for anti-CCP antibody. The simple preparation method endows the good reproducibility and stability for the proposed ECL immunosensor. A wide linear range of 0.001 ∼ 15 ng mL −1 with a lower detection limit of 0.2 pg mL −1 was obtained for the determination of anti-CCP antibody. The proposed ECL method may has promising application in other bioassays. [ABSTRACT FROM AUTHOR]

Hyperviscosity syndrome (HVS) develops most commonly in Waldenström's macroglobulinemia (WM) and multiple myeloma (MM). Plasmapheresis is the immediate therapy and very effective at relieving symptoms by removing paraprotein. The most commonly used replacement fluid is 4%–5% human albumin in physiologic saline. FFP may be used in patients with coagulation abnormalities. Plasmapheresis should be continued until acute symptoms abate. Hyperviscosity impairs the circulation in the retina and causes hemorrhages around the small retinal vessels. Early diagnosis and urgent plasmapheresis may reduce blindness caused by retinal hemorrhages and/or retinal detachment. In HCV related mixed cryoglobulinemias, plasmapheresis is indicated if rapidly evolving life-threatening disease with immunosuppressive agent exists. In non-infectious mixed cryoglobulinemia plasmapheresis is indicated when the disease manifestations are severe, as a second line option. In WM patients with hyperviscosity symptoms and IgM > 4 g/dL, preemptive plasmapheresis is recommended to prevent an IgM flare with rituximab. Certain IgG/A MGUS-associated neuropathy patients may benefit from plasmapheresis. For cast nephropathy (suspected or biopsy proven), plasmapheresis is recommended when the sFLC ≥ 500 mg/l and as early as possible (<1 month with kidney injury). Theoretically, extracorporeal removal alone, without efficient tumor killing, could not reduce sFLC due to high production by the tumor mass and rapid rebound between compartments. [ABSTRACT FROM AUTHOR]

Background: When there is no authorized on- or in absence even no off-label treatment for patients with rare diseases, pharmacists have to compound medicinal products to meet the patients special needs. However it is important that there is evidence in the medical and/or pharmaceutical literature for such compounded medications.Position Statement: Pharmaceutical compounding must be performed in the best possible circumstances by certified practitioners (pharmacists) using validated standard operating procedures (standardized formulations) in order to obtain medicinal products of the highest quality to assure patient safety. More than 60 compounding procedures were identified in 17 on-line pharmaceutical compounding reference sources worldwide but more operating procedures still need to be validated. All ingredients used in the preparation of the compounded medication must be accompanied by a certificate of analysis and full records of the pharmaceutical production process need to be kept for full traceability and accountability. [ABSTRACT FROM AUTHOR]

Type XVII collagen ( COL17) and the non-collagenous 16A ( NC16A) domain is regarded as the major pathogenic domains for bullous pemphigoid ( BP). Some patients with BP have autoantibodies against parts of COL17 outside the NC16A domain (hereinafter the non- NC16A domain) and show less inflammatory manifestations. There were no significant differences in titres and IgG subclasses between NC16A- BP and non- NC16A- BP as determined by indirect immunofluorescent microscopy. The neutrophil activation capacities determined by ROS release did not differ between NC16A- BP and non- NC16A- BP. However, NC16A- BP IgG depleted COL17 in a dose-dependent manner. Treatment with NC16A- BP IgG, but not with non- NC16A- BP IgG, significantly decreased the adhesion strength. We speculate that the differences in clinical severity between NC16A- BP and non- NC16A- BP relate to the degree of COL17 depletion. [ABSTRACT FROM AUTHOR]

Background & objectives: In patients with rheumatoid arthritis (RA), disease severity assessment is done using Disease Activity Score in 28 joints with ESR (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an online calculator. There is a need to validate rapid methods of disease severity assessment for routine daily use. This study was conducted to compare DAS28, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3 measures (RAPID3) to assess the disease activity in patients with RA. Methods: We prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100 consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naïve adult patients with RA seen during January 2013 and June 2014 at a tertiary care teaching hospital in south India. Results: The mean age of the patients was 42.1±11.6 yr, there were 82 females. The median [interquartile range (IQR)] symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQDI and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13-19), respectively. A significant positive correlation was observed between DAS28 and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust. Interpretation & conclusions: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation. [ABSTRACT FROM AUTHOR]

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia®) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical effectiveness review identified no head-to-head evidence on the efficacy of CZP against the comparators within the scope; therefore, the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems, each of which followed an inadequate response to a TNFi. These were (1) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (2) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (3) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in a similar number of quality-adjusted life years (QALYs) produced at similar or lower costs compared with comparator bDMARDs. The commercial-in-confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX produced more QALYs at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced fewer QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not tolerated. The AC concluded that CZP plus MTX could not be considered a cost-effective use of National Health Service resources when RTX plus MTX is a treatment option. [ABSTRACT FROM AUTHOR]

The use of DBSs for home monitoring has been limited due to unsatisfactory blood sampling and analytical difficulties. The aim of this longitudinal feasibility trial was to assess the utility of DBS to monitor TAC and Cr at home in transplant recipients. A total of 30 participants (2-21 years, mean±SD, 13.6±5.4 year) were enrolled over 12 months. Eighteen were males. Monthly DBS samples were obtained at home and mailed to the central laboratory for analysis of TAC and Cr. Nineteen patients completed the study, and 216 cards were received in the laboratory from a total of 279 cards expected, with 416/519 (80%) blood spots being suitable for analysis. We found a high correlation between blood TAC and Cr levels by DBS and the clinical laboratory, R2=.81 and .95, respectively. Fifteen parents and 15 youth completed measures of satisfaction with and preference for DBS testing. All but one parent/caregiver and youth reported satisfaction and preference for this method of testing over laboratory blood draws. We conclude that home DBS monitoring is a feasible method to monitor TAC and Cr in pediatric transplant recipients. [ABSTRACT FROM AUTHOR]

In this brief review, we have examined some clinical conditions that result to be associated to an altered hemorheological profile and at times accompanied by skin ulcers. This skin condition may be observed in patients with the following condtions, such as primary polycythemic hyperviscosity (polycythemia, thrombocytemia) treated with hydroxyurea, primary plasma hyperviscosity (multiple myeloma, cryoglobulinemia, cryofibrinogenemia, dysfibrinogenemia, and connective tissue diseases), primary sclerocythemic hyperviscosity (hereditary spherocytosis, thalassemia, and sickle cell disease). In addition, it may be present in patients with secondary hyperviscosity conditions such as diabetes mellitus, arterial hypertension, critical limb ischemia and chronic venous insufficiency. [ABSTRACT FROM AUTHOR]

The greatest ambition and promise of tissue engineering is to manufacture human organs. Before “made-to-measure” tissues can become a reality [1–3] , however, three-dimensional tissues must be reconstructed and characterized. The current inability to manufacture operational vasculature has limited the growth of engineered tissues. Here, free-standing, small diameter blood vessels with organized cell layers that recapitulate normal biological functionality are fabricated using microfluidic technology. Over time in culture, the endothelial cells form a monolayer on the luminal wall and remodel the scaffold with human extracellular matrix proteins. After integration into three-dimensional gels containing fibroblasts, the microvessels sprout and generate extended hollow branches that anastomose with neighboring capillaries to form a network. Both the microfabricated vessels and the extended sprouts support perfusion of fluids and particles. The ability to create cellularized microvessels that can be designed with a diameter of choice, produced by the meter, and undergo angiogenesis and anastomoses will be an extremely valuable tool for vascularization of engineered tissues. To summarize, ultraviolet (UV) photo-crosslinkable poly(ethylene glycol) and gelatin methacrylate polymers used in combination with sheath-flow microfluidics allow for the fabrication of small diameter blood vessels which undergo neoangiogenesis as well as other developmental processes associated with normal human blood vessel maturation. Once mature, these vessels can be embedded; perfused; cryogenically stored and respond to stimuli such as chemokines and shear stresses to mimic native human blood vessels. The applications range from tissue-on-chip systems for drug screening, characterization of normal and pathologic processes, and creation and characterization of engineered tissues for organ repair. [ABSTRACT FROM AUTHOR]