Maintenance of efficacy and its predictors after discontinuation of eltrombopag in adults with primary immune thrombocytopenia / 中华血液学杂志

Objective: To determine the efficacy of eltrombopag for primary immune thrombocytopenia (ITP) in adults and the predictive factors for treatment-free response (TFR) . Methods: Clinical data of adults with ITP who received eltrombopag from June 14, 2013 to May 31, 2021 in the Hematology Department of Ruijin Hospital affiliated with Shanghai Jiao Tong University Medical College were retrospectively analyzed. The initial dose of eltrombopag was 25 mg/d, and the maximum dose was 75 mg/d; the dose was adjusted to maintain the platelet count to within 50-150×10(9)/L. Treatment was discontinued according either to the protocol, on the patient's wishes or doctor's judgment (prescription medication), or based on clinical trials. The efficacy of eltrombopag and factors for TFR among patients who achieved complete response and those who discontinued treatment were analyzed. Results: Overall, 106 patients with ITP (33 men and 73 women) were included in the study. The median age of patients was 50 (18-89) years. There were 2, 10, and 94 cases of newly diagnosed, persistent, and chronic ITP, respectively. The complete response rate was 44.3% (47/106), the response rate was 34.0% (36/106), and the overall response rate was 78.3% (83/106). Meanwhile, 83 patients who responded to treatment discontinued eltrombopag; of these, 81 patients were evaluated. Additionally, 17 patients (21.0%) achieved TFR. The median follow-up duration of patients who achieved TFR was 126 (30-170) weeks. The recurrence rate was 17.6% (3/17), and the relapse-free survival rate was 76.5%. The results of univariate analysis revealed that non-recurrence after discontinuation of other treatments for ITP (P=0.001), and platelet count and eltrombopag dose of ≥100×10(9)/L (P=0.007) and ≤25 mg/d (P=0.031), respectively, upon discontinuation of eltrombopag were predictors of TFR; these effects were attributed to prolonged effective duration of eltrombopag. Multivariate analysis showed that there was a correlation between non-recurrence and prolonged effective duration after discontinuation of other treatments for ITP (P=0.002) . Conclusion: Eltrombopag is effective for patients with ITP as it can result in TFR. Predictors for TFR include non-recurrence after discontinuation of concomitant ITP treatment, and platelet count and eltrombopag dose of ≥100 × 10(9)/L and ≤25 mg/d upon discontinuation of treatment, respectively.

Development of fixed-time artificial insemination protocols for locally adapted Curraleiro Pé-Duro cows / Desenvolvimento de protocolos de inseminação artificial em tempo fixo em vacas da raça localmente adaptada Curraleiro Pé-Duro

Two experiments were conducted aiming to evaluate the effects of two ovulatory inducers (Exp.1) and equine chorionic gonadotropin (eCG; Exp.2) on follicular and luteal dynamics in a fixed-time AI (FTAI) protocol in locally adapted Curraleiro Pé-Duro cows. In Exp. 1 multiparous cows (n=12) received an intravaginal device containing 1g of progesterone (P4) for 8 days and 2mg of estradiol benzoate (EB) intramuscularly (IM) at device insertion (Day 0). At device removal (Day 8) 0.150mg of Sodium D-Cloprostenol was administered IM and the cows were randomly assigned to receive 1mg of EB (EB8) or 1mg of estradiol cypionate (EC8) IM, or to not receive any ovulatory inducer (Control). All the animals participated in all treatments (crossover). The interval from P4 removal to ovulation was shorter and less variable in the EB8 treatment group (P≤0.05). In Exp. 2 (crossover), multiparous cows (n=12) received the same hormonal treatment as the EB8 group in Exp.1. At device removal (Day 8) cows were randomly assigned to receive 300UI of eCG IM or to not receive eCG (Control). No difference was ascertained on follicular and luteal parameters in Exp. 2 (P>0.05). We concluded that EB can be used as the ovulatory inducer (Exp. 1) in a FTAI protocol in Curraleiro Pé-Duro cows. However, eCG (Exp. 2) was not able to stimulate follicular and luteal development. This result is probably due to the adaptive capacity of Curraleiro Pé-Duro cows that maintained a satisfactory body condition score even in dry and hot environments.(AU)

Foram realizados dois experimentos com o objetivo de avaliar o efeito de dois indutores da ovulação e da gonadotrofina coriônica equina (eCG) na dinâmica folicular e luteal, em um protocolo de inseminação artificial em tempo fixo (IATF) em vacas localmente adaptadas da raça Curraleiro Pé-Duro. No experimento 1, vacas pluríparas receberam um dispositivo intravaginal contendo 1g de progesterona (P4) durante oito dias e 2mg de benzoato de estradiol (BE) intramuscular (IM) no momento da inserção do dispositivo (dia zero). Na retirada do dispositivo (dia oito), as vacas receberam 0,150mg de D-cloprostenol sódico IM e foram separadas aleatoriamente para receber 1mg de BE IM (BE8) ou 1mg de cipionato de estradiol IM (CE8), ou nenhum indutor da ovulação (controle). Todos os animais participaram de todos os tratamentos (crossover). O intervalo entre a retirada da P4 e a ovulação foi menor e menos variável no tratamento BE8 (P≤0,05). O momento da ovulação foi mais precoce e mais concentrado nos animais do grupo BE 8. No experimento 2 (crossover), vacas pluríparas receberam o mesmo tratamento hormonal do grupo BE8 do experimento1. Na retirada do dispositivo (dia 8), as vacas foram separadas aleatoriamente para receberem 300UI de eCG IM, enquanto o controle não. Não houve diferença nos parâmetros foliculares e luteais avaliados no experimento 2 (P>0,05). Em conclusão, o BE pode ser utilizado como indutor da ovulação (experimento 1) em protocolos de IATF em vacas Curraleiras Pé-Duro. Entretanto, o eCG (experimento 2) não foi capaz de estimular o desenvolvimento folicular e luteal. Esse resultado é devido provavelmente à capacidade adaptativa das vacas Curraleiras Pé-Duro em manter uma condição corporal satisfatória mesmo em condições de clima seco e quente.(AU)

Korean Guideline for Iron Chelation Therapy in Transfusion-Induced Iron Overload

Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

Iron Overload during Follow-up after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients with High-Risk Neuroblastoma

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

Past, present & future scenario of thalassaemic care & control in India.

The first case of thalassaemia, described in a non-Mediterranean person, was from India. Subsequently, cases of thalassaemia were documented in all parts of India. Centres for care of thalassaemics were started in the mid-1970s in Mumbai and Delhi, and then in other cities. The parent's associations, with the help of International Thalassemia Federation, greatly helped in improving the care of thalassaemics. Obtaining blood for transfusion was difficult, but the Indian Red Cross Society and the parent's associations played a crucial role in arranging voluntary donations of blood. Chelation with deferoxamine was used sparingly due to the high cost. The Indian physicians conducted trials with deferiprone, and the drug was first approved and marketed in India. Deferasirox is also now being administered. Studies of physical and pubertal growth documented significant retardation, suggesting that generally patients receive inadequate chelation and transfusions. Bone marrow transplantation is available at a number of centres, and cord blood stem cell storage facilities have been established. Information about mutations in different parts of India is available, and ThalInd, an Indian database has been set up. There is a need to set up preimplantation genetic diagnosis and non-invasive prenatal diagnosis. It is argued that too much emphasis should not be placed on premarital screening. The focus should be on screening pregnant women to yield immediate results in reducing the burden of this disorder. Care of thalassaemia has been included in the 12th 5-year Plan of the Government of India. Many States now provide blood transfusions and chelation free of cost. Although inadequacies in care of thalassaemia remain, but the outlook is bright, and the stage is set for initiating a control programme in the high risk States.

Anti-albuminuric efficacy of a combination of angiotensin converting enzyme inhibitor & angiotensin receptor blocker in type 1 DM with nephropathy.

Background & objective: The efficacy of the combination of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria were evaluated. Methods: In this open label observational study 30 patients (20 male 10 female) with type 1 DM were included who were initially treated with telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a further eight weeks. Albuminuria reduction was studied at the end of each phase. Results: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01) reduction in albumin excretion rate (AER). Combination therapy with telmisartan and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01), amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was more effective in the group of macroalbuminuric as compared to microalbuminuric subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05). The addition of ramipril produced a further reduction in BP, the total reduction being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the study period and two patients had hyperkalemia > 5.5 mmol/l with dual blockade. Interpretation & conclusion: Dual blockade with ramipril enhanced the antialbuminuric efficacy of telmisartan and further reduced blood pressure. The effect of dual blockade was more pronounced in the macroalbuminuric subjects and it was well tolerated. However, careful monitoring of serum potassium is required.

Deferasirox: Oral, once daily iron chelator - An expert opinion.

Iron overload is a serious and potentially fatal condition that results from multiple blood transfusions required over a long period of time to treat certain types of anemias such as, that caused by β-thalassemia, sickle cell disease and myelodysplastic syndrome. Deferoxamine, which has been used since four decades as an iron chelator has limited efficacy due to its demanding therapeutic regimen, leading to poor compliance. Deferasirox, once daily oral iron chelator provides an effective alternative to Deferoxamine in the treatment of transfusional hemosiderosis. In this review, the role of Deferasirox as an ideal iron chelator has been discussed. Pubmed searches on Deferasirox were carried out for the same. Several studies demonstrated the safety and efficacy of Deferasirox in reducing iron burden in iron-overloaded patients with β-thalassemia, sickle cell anemia and myelodysplastic anemia. Thus, convenient, effective and tolerable chelation therapy with oral Deferasirox is likely to be a significant development in the treatment of transfusional iron overload, due to its ability to provide constant chelation coverage and the potential to improve compliance.

Sarna costrosa (Noruega): presentación de un caso clínico / Crusted scabies (Norwegian scabies): a case report

Diferentes tipos de sarna han sido descritos con base en sus características clínicas, entre ellos la sarna costrosa (Noruega). Es una manifestación rara y extrema de la escabiosis que se produce principalmente en pacientes inmunosuprimidos. Se presenta el caso de un hombre de 42 años, homosexual, a quien se diagnosticó VIH y que presenta lesiones dérmicas pruriginosas de 4 meses de evolución en tronco y extremidades, constituidas por xerosis, pápulas decapitadas, placas eritematosas, manchas hipercrómicas residuales y múltiples excoriaciones e hiperpigmentación ungueal en ambos pies. Se trató inicialmente como dermatitis psorasiforme que no cedió al tratamiento con esteroides y antipruritico. Se realizó diagnóstico por biopsia que confirmó la sospecha clínica de sarna noruega. Se aplicó un tratamiento con una dosis de ivermectina oral y benzoato de bencilo tópico con remisión en dos días.

Different types of scabies have been described based on their clinical outcome, one of which is the Crusted (Norwegian) type. This is an extreme manifestation of scabies that can be observed mainly among immunosupressed patients. A case ofa 42 year-old homosexual man is described. The patient was diagnosed with HIV, presenting pruritic lesions with a 4 month evolution in trunk and extremities. Lesions included xerosis, decapitated papules, badges with erythema, residual hyperchromic stains, multiple abrasions and ungueal pigmentation in both feet. At the beginning it was treated as apsorasiform dermatitis with steroids and antipruritics without success. Through a biopsy the suspected diagnosis of Crusted (Norwegian) scabies was confirmed. The patient was treated with a dose of oral ivermectin and topical benzyl benzoate and showed remission after two days.

Efecto de la combinación de benzoato de sodio con lactulosa en la hiperamonemia experimental / Effect of sodium benzoate plus lactulose combination in experimental hyperammonemia

El benzoato de sodio se ha utilizado en el tratamiento de la encefalopatía hepática hiperamonémica con buenos resultados. Con el objeto de investigar si la combinación de benzoato de sodio con un disacárido (lactosa, lactulosa) tiene un efecto aditivo sobre la disminución de amonio plasmático, se estudió el efecto de la combinación de benzoato de sodio con lactulosa en el modelo de anastomosis portocava en la rata, ya que éste es el modelo experimental que produce mayores elevaciones de amonio en sangre. Se utilizaron ratas Wistar de 250-300 g de peso en las que se practicó una anastomosis porto-cava terminolateral. Diez días después de la operación se inició tratamiento experimental por un periodo de siete días, dividiendo a los animales en cuatro grupos: a) solución salina, b) B.S. 500 mg/kg/día, c) lactulosa 4 g/kg/día, d) benzoato de sodio más lactulosa (dosis anotadas). También se incluyeron un grupo de ratas normales y un grupo con operación ficticia como controles. Se tomaron muestras de sangre arterial al final del periodo de estudio y se determinó amonio por el método enzimático. Resultados. El benzoato de sodio y la lactulosa disminuyeron significativamente las concentraciones de amonio plasmático (437ñ50, 433ñ85 ug/dl, respectivamente) en comparación con el grupo control (638 ñ 50 ug/dl, p = 0.05), tal como se esperaba. La combinación de benzoato de sodio con lactulosa produjo una disminución de amonio aún mayor (264 ñ 17 ug/dl, p<0.001), lo cual apoya la existencia de un efecto aditivo entre ambos fármacos. Estos hallazgos parecen reproducirse en la clínica de acuerdo a estudios clínicos preliminares en los que se ha utilizado la combinación de lactosa con benzoato de sodio. Estos resultados sugieren que puede haber un efecto aditivo entre el benzoato de sodio y disacáridos como la lactulosa, lo cual podría aumentar la eficiencia del tratamiento e incluso disminuir la dosis total de medicamentos y aumentar la tolerancia a cada uno de los fármacos. Finalmente, se plantea la posibilidad de emplear otros fármacos derivados del benzoato de sodio

Medicamentos ectoparasiticidas: risco e benefício / Ectoparasiticides drugs: risk and benefit

A escolha de produtos ectoparasiticidas para uso humano deve obedecer certos critérios, principalmente envolvendo a relaçäo risco-benefício, desde que muitos säo substâncias capazes de destruir formas de vida. As relaçöes adversas, os efeitos colaterais, a toxicidade, aliados a fatores como formulaçöes, interaçäo medicamentosa, incompatibilidades, freqüência das aplicaçöes e outras vias de penetraçäo orgânica devem ser avaliados. O trabalho se propöe a atualizar e revisar os dados farmacológicos e toxicológicos dos ectoparasiticidas mais freqüentemente utilizados para adequar a sua escolha

Valoración mediante estudio doble ciego de la combinación de tartrato de ergotamina, acetofenetidina, ácido acetilortoxibenzoico y trimetilxantina en el tratamiento de cefalea vascular tipo migraña / Evaluation by double-blind study of the combination of ergatomine tartrate, acetophenetidine, acetytorthoxybenzoic acid and trimethylxantine, in the treatment of migraine-type vascular cephalea

En el servicio de neurología del Hospital Central Militar de la ciudad de México, se estudió a 60 pacientes con diagnóstico de cefalea vascular tipo migraña, clásica y común. Se valoró la eficiencia y posibles efectos indeseables, mediante estudio doble ciego, de las siguintes combinaciones de medicamento: 1) mesilato de dihidroergotamina, cafeína, butalbital y propifenazona; 2) tartrato de ergotamina y cafeína; y 3) tartrato de ergotamina, acetofenetidina, ácido acetilortoxibenzoico y trimetilxantina

Acción del benfluorex en pacientes con sobrecargas metabólicas: estudio preliminar / Action of benfluorex in patients with metabolic surcharge: preliminary study

Se estudiaron 16 pacientes con polisobrecargas metabólicas (hiperlipidemias, hiperglicemias). Todos fueron estudiados según el siguiente diseño experimental: a) Dos semanas de lavado. b) Ocho semanas de tratamiento con Benfluorex a dosis de 450 mg/día, p.o. c) Ocho semanas con placebo más dieta. d) Cuatro semanas con Benfluorex (450 mg/día, p.o.) más dieta. El colesterol total descendió con Benfluorex y este descenso fue mayor al agregar la dieta. Lo mismo sucedió con los triglicéridos. La HDL-colesterol ascendió, mientras que la LDL-colesterol descendió, por lo que el índice LDL-C/HDL-C disminuyó con el tratamiento, indicando menor riesgo de aterogenesis. La glicemia descendió también significativamente, sin llegar a los límites de hipoglicemia. El ácido úrico no descendió significativamente, pero hay que tener en cuenta que los valores de la uricemia no estaban muy elevados antes de cocmenzar el tratamiento. En conclusión, los resultados preliminares de este trabajo muestran una acción significativa del Benfluorex sobre las hiperlipidemias, las hiperglicemias o hiperuricemias con muy pocos efectos secundarios

Doença de Peyronie: avaliaçäo do tratamento com aminobenzoato de potássio (potaba) / Peyronic's disease: avaliation of the treatment with potassium amino-benzoate

Os autores apresentam 30 casos da doença de Peyronie, tratados com aminobenzoato de potássio, em que 17 foram considerados curados. Recomendam o aminobenzoato de potássio como tratamento de escolha, ficando o tratamento cirúrgico para os casos que näo apresentarem melhora