Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy

The Financial Implications of Mandating Non-Financial Assurance

This paper examines the impact on audit effort of requiring the assurance of non-financial information. Specifically, we use a sample of large New Zealand not-for-profits (charities) newly required to report and have assured statements of service performance following accounting and auditing standards. We find an increase in audit fees of 14.5%, although there is no change in audit or filing lag. There is no difference based on auditing standard used, audit firm or whether an ‘other matter’ is expressed in the audit report. Overall, our results suggest that mandating the reporting and assurance of non-financial information should be viewed as having greater costs than adopting International Financial Reporting Standards

“En-Solex”: A Novel Solar Exoskeleton for the Energy-efficiency Retrofitting of Existing Buildings

The energy retrofitting of the existing building stock is one of the current challenging strategic objectives on the way to the European target of climate neutrality by 2050. According to the Renovation Wave plan, around 35 million existing buildings need to be upgraded to the highest energy efficiency level by 2030, and innovative technological solutions are required to achieve this ambitious goal. This paper proposes a novel solar exoskeleton for the energy and architectural retrofitting of existing buildings, called En-Solex. The system, which consists of an external steel frame that wraps around buildings like a double skin, combines passive solar gain control (shading and greening) with high-efficiency active solar systems (PV panels) optimised for integration into existing building facades. The energy-saving potential of the system with different façade configurations is evaluated on a multi-family residential building located in a Mediterranean climate. The dynamic energy simulations show that the proposed solution can reduce the energy demand for space heating and cooling by 33.4% and 25.5% respectively. The En-Solex system integration combined with generator replacement results in a maximum heating and cooling reduction equal to 80.7% and 59.6% respectively. The surplus of electricity generated, thanks to the integration of RES, can lead to a net plus target, with the building exceeding its average annual electricity demand

Management of Cancer-Related Anemia with Erythropoietic Agents: Doubts, Certainties, and Concerns

Abstract The management of cancer-related anemia with erythropoietic agents presents many unresolved issues. We reviewed the literature relating to epoetin alfa (Eprex®/Epypo®; Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit®; Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com), epoetin beta (NeoRecormon®; Hoffman-La Roche, Basel, Switzerland, http://www.roche.com), and darbepoetin alfa (Aranesp®; Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) highlighting the results of published clinical trials, safety, and cost-effectiveness. Studies were identified through MEDLINE and the bibliographies of relevant articles. Epoetin alfa, epoetin beta, and darbepoetin alfa have differing pharmacokinetic and pharmacodynamic profiles. They are all effective at reducing transfusion requirements and improving health-related quality-of-life parameters, irrespective of tumor response. A direct comparison between epoetin alfa and darbe poetin alfa is based on limited evidence, which does not allow definitive conclusions about relative efficacy and cost-effectiveness. No predictive factors for response to erythropoietic agents have been validated in prospective trials. The most consistent adverse events are thrombotic and may occur irrespective of an increase in hemoglobin. Recent research indicates that the erythropoietin receptor is expressed in several cancer cell lines, raising the concern of possible stimulation of tumor cell growth by these drugs. Studies on the cost-effectiveness of erythropoietins, particularly compared with transfusion therapy, have been challenging to conduct and analyze and have generated ambiguous results. The use of erythropoietins needs to be optimized in terms of cost-effectiveness, and issues surrounding safety need to be clarified. A stronger methodology for clinical studies and the design of new, randomized, clinical trials is a major priority

Long-Term Outcome of Otherwise Healthy Individuals with Incidentally Discovered Borderline Thrombocytopenia

BACKGROUND: The long-term outcome of individuals with mild degrees of thrombocytopenia is unknown. METHODS AND FINDINGS: In a prospective study conducted between August 1992 and December 2002, 260 apparently healthy individuals with incidentally discovered platelet counts between 100 × 10(9)/l and 150 × 10(9)/l were monitored for 6 mo to determine whether their condition persisted. The monitoring period was completed in 217 cases, of whom 191 (88%) maintained stable platelet counts. These 191 individuals were included in a long-term follow-up study to gain knowledge of their natural history. With a median time of observation of 64 mo, the thrombocytopenia resolved spontaneously or persisted with no other disorders becoming apparent in 64% of cases. The most frequent event during the study period was the subsequent development of an autoimmune disease. The 10-y probability of developing idiopathic thrombocytopenic purpura (ITP), as defined by platelet counts persistently below 100 × 10(9)/l, was 6.9% (95% confidence interval [CI]: 4.0%–12.0%). The 10-y probability of developing autoimmune disorders other than ITP was 12.0% (95% CI: 6.9%–20.8%). Most of the cases (85%) of autoimmune disease occurred in women. CONCLUSIONS: Healthy individuals with a sustained platelet count between 100 × 10(9)/l and 150 × 10(9)/l have a 10-y probability of developing autoimmune disorders of 12%. Further investigation is required to establish whether this risk is higher than in the general population and whether an intensive follow-up results in an improvement of prognosis

CK2 modulates adipocyte insulin-signaling and is up-regulated in human obesity

Insulin plays a major role in glucose metabolism and insulin-signaling defects are present in obesity and diabetes. CK2 is a pleiotropic protein kinase implicated in fundamental cellular pathways and abnormally elevated in tumors. Here we report that in human and murine adipocytes CK2-inhibition decreases the insulin-induced glucose-uptake by counteracting Akt-signaling and GLUT4-translocation to the plasma membrane. In mice CK2 acts on insulin-signaling in adipose tissue, liver and skeletal muscle and its acute inhibition impairs glucose tolerance. Notably, CK2 protein-level and activity are greatly up-regulated in white adipose tissue from ob/ob and db/db mice as well as from obese patients, regardless the severity of their insulin-resistance and the presence of pre-diabetes or overt type 2 diabetes. Weight loss obtained by both bariatric surgery or hypocaloric diet reverts CK2 hyper-activation to normal level. Our data suggest a central role of CK2 in insulin-sensitivity, glucose homeostasis and adipose tissue remodeling. CK2 up-regulation is identified as a hallmark of adipose tissue pathological expansion, suggesting a new potential therapeutic target for human obesity

T1 Bladder Cancer: Comparison of the Prognostic Impact of Two Substaging Systems on Disease Recurrence and Progression and Suggestion of a Novel Nomogram

Background: The T1 substaging of bladder cancer (BCa) potentially impacts disease progression. The objective of the study was to compare the prognostic accuracy of two substaging systems on the recurrence and progression of primary pathologic T1 (pT1) BCa and to test a nomogram based on pT1 substaging for predicting recurrence-free survival (RFS) and progression-free survival (PFS).Methods: The medical records of 204 patients affected by pT1 BCa were retrospectively reviewed. Substaging was defined according to the depth of lamina propria invasion in T1(a-c) and the extension of the lamina propria invasion to T1-microinvasive (T1(m)) or T1-extensive (T1(e)). Uni- and multivariable Cox regression models evaluated the independent variables correlated with recurrence and progression. The predictive accuracies of the two substaging systems were compared by Harrell's C index. Multivariate Cox regression models for the RFS and PFS were also depicted by a nomogram.Results: The 5-year RFS was 47.5% with a significant difference between T1(c) and T1(a) (p = 0.02) and between T1(e) and T1(m) (p < 0.001). The 5-year PFS was 75.9% with a significant difference between T1(c) and T1(a) (p = 0.011) and between T1(e) and T1(m) (p < 0.001). Model T1(m-e) showed a higher predictive power than T1(a-c) for predicting RFS and PFS. In the univariate and multivariate model subcategory T1e, the diameter, location, and number of tumors were confirmed as factors influencing recurrence and progression after adjusting for the other variables. The nomogram incorporating the T1(m-e) model showed a satisfactory agreement between model predictions at 5 years and actual observations.Conclusions: Substaging is significantly associated with RFS and PFS for patients affected by T1 BCa and should be included in innovative prognostic nomograms

Flow-diverter treatment for renal artery aneurysms: One-year follow-up of a multicentric preliminary experience

PURPOSERenal artery aneurysms (RAAs) are rare in the general population, although the true incidence and natural history remain elusive. Conventional endovascular therapies such as coil embolization or covered stent graft may cause sidebranches occlusion, leading to organ infarction. Flow-diverters (FD) have been firstly designed to treat cerebrovascular aneurysms, but their use may be useful to treat complex RAAs presenting sidebraches arising from aneurysmal sac. To evaluate mid-term follow-up (FUP) safety and efficacy of FD during treatment of complex RAAs.METHODSBetween November 2019 and April 2020, 7 RAAs were identified in 7 patients (4 men, 3 women; age range 55-82 years; median 67 years) and treated by FD. Procedural details, complications, morbidity and mortality, aneurysm occlusion and segmental artery patency were retrospectively reviewed. Twelve months computed tomography angiography (CTA) FUP was evaluated for all cases.RESULTDeployment of FD was successful in all cases. One intraprocedural technical complication was encountered with one FD felt down into aneurism sac which requiring additional telescopic stenting. One case at 3 months CTA FUP presented same complication, requiring same rescue technique. At 12 months CTA FUP 5 cases of size shrinkage and 2 cases of stable size were documented. No rescue surgery or major intraprocedural or mid-term FUP complication was seen.CONCLUSIONComplex RAAs with two or more sidebranches can be safely treated by FD. FD efficacy for RAA needs a further validation at long term FUP by additional large prospective studies