Repeated successful use of eltrombopag in chronic primary immune thrombocytopenia: description of an intriguing case.

Thrombopoietin receptor agonists (TPO-RAs) are used as effective alternative treatments in ITP patients unresponsive to first-/second-line therapies. TPO- RAs can also be used to normalize platelet count to safely perform invasive pro- cedures and chemotherapy, in case of malignancies. In few responsive patients, TPO-RAs can be suspended maintaining a sustained respons

Clinical characteristics and outcome of patients with autoimmune hemolytic anemia (AIHA) uniformly defined as primary by a diagnostic work-up

Primary autoimmune hemolytic anemia (P-AIHA) is a relatively uncommon and hetereogeneous disease characterized by the destruction of red blood cells due to anti-erythrocyte autoantibodies (AeAbs) in the absence of an associated disease [1–3]. Secondary AHIA is frequently associated with lymphoproliferative diseases (LD) in particular, chronic lymphocytic leukemia, aggressive or indolent lymphomas, autoimmune disorders, malignancies other than lymphoid, and infections [1,2,4]. On the hypothetical assumption that in a significant proportion of cases defined as P-AIHA the clinical heterogeneity could be due to an ignored associated disease, we retrospectively analyzed the clinical characteristics and outcome of patients with a diagnosis of P-AIHA based on a diagnostic work-up aimed at excluding or identifying an associated disease. ..

The Von Willebrand factor-ADAMTS-13 axis: a two-faced Janus in bleeding and thrombosis

Von Willebrand factor (VWF), a blood multimeric protein with a very high molecular weight, plays a crucial role in the primary hemostasis, the physiological process characterized by the adhesion of blood platelets to the injured vessel wall. Hydrodynamic forces are responsible for the VWF multimers conformational transitions from a globular to a stretched linear conformation. These characteristics render this protein a valuable object to be investigated by mechanochemistry, the biophysical chemistry branch that studies the effects of shear forces on protein conformation. This review will focus on the structural elements of the VWF molecule involved in the biochemical response to shear forces. The stretched VWF conformation favors the interaction with the platelet GpIb and at the same time with ADAMTS-13, the zinc-protease that cleaves VWF in the A2 domain, limiting its prothrombotic capacity. It is important to consider the level or the function of VWF or ADAMTS-13 always in relation each other, keeping in mind that in many thrombotic forms of microangiopathies the reduction of the ratio between the ADAMTS-13 activity and the VWF level (lower than 0.5) can be a valuable parameter to predict a real thrombotic risk. Hence, a significant increase in VWF level alone, even without any reduction of ADAMTS-13 concentration, would still be responsible for a significant reduction of the ADAMTS-13/VWF ratio, which ultimately could reflect or predict a prothrombotic risk. Future studies will have to validate the concept whether ADAMTS-13/VWF ratio could a valuable and reliable biomarker to predict or confirm the presence of thrombotic risk in several morbid conditions

Management of elderly and unfit patients with chronic lymphocytic leukemia

Introduction: About 75% of patients with chronic lymphocytic leukemia (CLL) are more than 65 years at the time of diagnosis. Treatment of the elderly remains complicated due to multiple factors, such as comorbidities, decline in functional reserve and fitness. Since chronological age by itself cannot properly predict life expectancy and treatment tolerance, an accurate assessment of the fitness status is of crucial importance for an optimal treatment choice. Areas covered: This review will discuss the most relevant aspects concerning the issues experienced in the management of elderly/unfit patients with CLL. The most frequently observed age-related toxicities, fitness assessments, supportive care measures and treatment options for elderly patients and for patients who are deemed unfit will be discussed. Literature search methodology included examination of PubMed index. Expert commentary: During the last decade, different trials focusing on elderly/unfit patients have investigated more tolerable chemoimmunotherapy schedules and, more recently, the activity and safety of chemo-free regimens. Chlorambucil combined with an anti-CD20 monoclonal antibody has shown clinical activity with a relatively good profile of toxicity. The recent introduction of the B-cell receptor antagonists, ibrutinib and idelalisib, and other targeted drugs in development (e.g. venetoclax), is broadening the therapeutic armamentarium of elderly CLL patients

Kajian Perbedaan Konsentrasi Larutan Garam Pada Perendaman Rgh Dan Vaksin Terhadap Kelulushidupan Dan Pertumbuhan Benih Ikan Lele Sangkuriang (Clarias Gariepinus)

Berdasarkan data KKP (2013), pencapaian produksi ikan lele pada tahun 2013 mampu melampaui target. Ikan lele merupakan ikan yang mudah dibudidayakan, sehingga banyak dilakukan penelitian agar didapatkan benih lele dengan pertumbuhan dan kelulushidupan yang lebih baik, serta tahan terhadap serangan penyakit. Penelitian ini bertujuan untuk mengetahui pengaruh konsentrasi larutan garam yang berbeda dan konsentrasi yang terbaik pada perendaman rGH dan vaksin terhadap kelulushidupan dan pertumbuhan benih lele sangkuriang. Penelitian ini dilaksanakan pada tanggal 13 November 2014 – 15 Februari 2015 di Satuan Kerja Pembenihan dan Budidaya Ikan Air Tawar (SATKER PBIAT), Siwarak, Ungaran, Semarang. Ikan uji yang digunakan adalah benih lele sangkuriang umur 12 hari. Metode yang digunakan adalah eksperimental dengan rancangan acak lengkap (RAL) 4 perlakuan dan 3 ulangan, yaitu: (A) perlakuan tanpa larutan garam, (B) konsentrasi 0,5%, (C) konsentrasi 1,0% dan (D) konsentrasi 1,5%. Pemeliharaan ikan dilakukan selama 42 hari. Variabel data yang diamati meliputi kelulushidupan, SGR, panjang mutlak, FCR, EPP dan kelulushidupan setelah uji tantang. Analisa data dengan menggunakan anova untuk mengetahui pengaruh perlakuan yang berbeda nyata, apabila hasil yang didapatkan berbeda nyata, maka dilanjutkan dengan uji duncan untuk mengetahui perlakuan yang terbaik. Hasil penelitian menunjukkan perlakuan terbaik adalah perlakuan C, dengan nilai kelulushidupan (87,00±1,00%), SGR (7,79±0,03%), nilai panjang mutlak (6,75±0,15cm), nilai FCR (0,71±0,01) dan nilai EPP (140,28±1,25%), sedangkan untuk kelulushidupan setelah uji tantang didapatkan hasil yang tidak berbeda nyata, dimana: A (93,33±5,77%), B (96,67±5,77%), C (96,67±5,77%) dan D (96,67±5,77%). Kesimpulan dari penelitian ini ialah pemberian konsentrasi larutan garam yang berbeda berpengaruh sangat nyata terhadap kelulushidupan, SGR, panjang mutlak, FCR dan EPP, namun tidak berpengaruh nyata terhadap kelulushidupan setelah uji tantang. Konsentrasi larutan garam terbaik pada penelitian ini adalah 1,0%. Based on data from KKP (2013), the achievement of the production of catfish in 2013 was able of exceeding the target. Catfish is a fish that easily cultivated, so a lot of research done to get catfish\u27s seed with better survival and growth, and it can resistant to attack of deseases. This research was aimed to find out the effect of different salt solution concentrations and the best concentration from immersion of rGH and vaccine for survival rate and growth of sangkuriang catfish\u27s seed. This research was conducted on November 13th, 2014 – February 15th, 2015 at Satuan Kerja Pembenihan dan Budidaya Ikan Air Tawar (SATKER PBIAT), Siwarak, Ungaran, Semarang. The fish that used for this research is sangkuriang catfish\u27s seed aged 12 days. Completely randomized design (CRD) was used in this research with four treatments and three replication, which treatments are: (A) without salt solution concentration, (B) Using concentration 0.5%, (C) Concentration 1.0% and (D) Concentration 1.5%. The Fishes are maintained for 42 days. Observational variable are survival rate, SGR, absolute length, FCR, EPP and survival rate after challenge test. Data analysis using anova to know the effect of treatment is significantly different, if the result is significantly different, then continue with duncan test to know the best treatment. The best result is treatment C, with survival rate (87.00±1.00%), SGR (7.79±0.03%), absolute length (6.75±0.15cm), FCR (0.71±0.01), EPP (140.28±1.25%), and for survival rate after challenge test are not significantly different, where: treatment A (93.33±5.77%), B (96.67±5.77%), C (96.67±5.77%) and D (96.67±5.77%). The conclusion of this research is giving of salt solution with different concentration take significantly effect for survival rate, SGR, absolute length, FCR and EPP, but did not take significantly effect for survival rate after challenge test. The best salt solution concentration is 1.0%

Ciona intestinalis interleukin 17-like genes expression is upregulated by LPS challenge

In humans, IL-17 is a proinflammatory cytokine that plays a key role in the clearance of extracellular bacteria promoting cell infiltration and production of several cytokines and chemokines. Here, we report on three Ciona intestinalis IL-17 homologues (CiIL17-1, CiIL17-2, CiIL17-3). The gene organisation, phylogenetic tree and modelling supported the close relationship with the mammalian IL-17A and IL-17F suggesting that the C. intestinalis IL-17 genes share a common ancestor in the chordate lineages. Real time PCR analysis showed a prompt expression induced by LPS inoculation suggesting that they are involved in the first phase of inflammatory response. In situ hybridization assays disclosed that the genes transcription was upregulated in the pharynx, the main organ of the ascidian immune system, and expressed by hemocytes (granulocytes and univacuolar refractile granulocyte) inside the pharynx vessels

Alterations in the α2 δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies

Objectives Thrombospondins, which are known to interact with the α2δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). Methods We measured the transcripts of thrombospondin-1 and α2δ subunit, and protein levels of α2δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Results Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. Significance These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs

Pediatric high-grade glioma: a heterogeneous group of neoplasms with different molecular drivers

High-grade gliomas(HGGs) in pediatric age have the same bad prognosis as those arising in adults. Approximately one-half of HGGs in children occur in the brain stem, most frequently within the pons as diffuse intrinsic pontine glioma or other midline structures. Although they have the same histological appearance of adult malignant gliomas, in recent years, the extensive use of molecular profiling techniques has demonstrated significant molecular differences between the two age groups. These data have led to a major reclassification of pediatric HGG (pHGG) based on molecular subgrouping with significant clinical correlations in terms of age at presentation, anatomical location, and prognosis. The most important molecular groups are: (1) the histone mutations related pHGG, that is, H3.K27-mutated midline and H3.G34-mutated hemispheric pHGG; (2) the rare isocitrate dehydrogenase (IDH)-mutated pHGG occurring mainly in adolescents; and (3) the H3-/IDH wild type, a heterogenous group of pHGG still object of further molecular stratification. Another important group of pHGG is that occurring in patients with cancer predisposition syndromes such as Li‑Fraumeni syndrome, constitutional mismatch repair deficiency, and neurofibromatosis‑1 (NF1). In this review, the different subgroups of pHGG and their major driver molecular alterations will be discusse

Right elbow arthropathy in a patient with severe haemophilia A

A 56‐year‐old male had been diagnosed with severe haemophilia A at the age of one year (missense mutation, exon 10, variant NM_000132.3c.1537+1G). He had been treated on demand with plasma‐derived factor VIII (pdFVIII) concentrate for most of his life; he was not compliant with prophylaxis and attended the clinic only when he thought it was strictly necessary. In April 2017 he underwent an orthopaedic assessment, which showed severe arthropathy of both elbows, knees and ankles. In August 2017, he attended the clinic with a major haemarthrosis of the right elbow, which had not resolved with self‐medication. On physical examination, the right elbow was deformed with multidirectional laxity; paradoxically the range of motion was preserved. An X‐ray of the right elbow showed severe arthropathy with complete joint dislocation (upper images). There were also widespread areas of erosion and absorption of the articular surfaces; these were confirmed on computed tomography (CT) scanning (lower left image). The patient was treated for six days with pdFVIII concentrate at a dosage of 50 U/kg/day, and then the frequency of infusions was decreased to every other day. After the acute phase, he continued with pdFVIII 40 U/kg every other day with continued clinical improvement. A peripherally inserted central catheter was used to improve compliance with intravenous infusions. In April 2018 a switch was made to extended half‐life FVIII concentrate (recombinant FVIII‐Fc fusion protein, rFVIII‐Fc, efmoroctocog alpha) to reduce the frequency of infusions. Thereafter the patient accepted prophylaxis with rFVIII‐Fc, at a dosage of 50 U/kg every 96 h, with a FVIII trough level of approximately 10% and stable joint status. Such severe joint damage is now uncommon in patients with haemophilia A. Our patient is a reminder of the possible consequences if prophylaxis is either unavailable or is not accepted by the patient