Efficacy of tamsulosin versus tadalafil as medical expulsive therapy on stone expulsion in patients with distal ureteral stones: A randomized double-blind clinical trial

ABSTRACT Purpose: To compare the effects of tadalafil, tamsulosin, and placebo as a medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods: This prospective randomized double-blind clinical trial was conducted on 132 renal colic patients with distal ureteric stones (≤10mm) over a period of 12 months. Patients were randomly divided into three groups. Patients in group A received tamsulosin 0.4mg, in group B received tadalafil 10mg, and in group C received placebo. Therapy was given for a maximum of 4 weeks. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results: Demographic profiles were comparable between the 3 groups. Although the stone expulsion rate in group A (72.7%) was higher in comparison to group B(63.6%) and group C(56.8%), it was not considered statistically significant (P=0.294). Shorter mean time to stone expulsion was significantly observed in group A (17.75±75), than group B(21.13±1.17) and group C(22.25±1.18) (P=0.47). The mean number of analgesic use was 9.8±5.09 days in group A, 14.6±7.9 days in group B, and 12.6±22.25 days in group C, this difference was significant (P=0.004). The analgesic requirement (doses of NSAIDs and pethidine) in group A was significantly lower than other groups (P<0.05). Also, patients in group A reported fewer headaches compared to other groups (P=0.011). Conclusion: Tamsulosin as medical expulsive therapy is more effective for distal ureteric stones with less need for analgesics and less stone expulsion time than tadalafil.

Adjunctive medical expulsive therapy with tamsulosin for repeated extracorporeal shock wave lithotripsy: a systematic review and meta-analysis

ABSTRACT Purpose: To evaluate the efficacy of adjunctive medical expulsive therapy (MET) with tamsulosin for the promotion of stone fragments clearance for repeated extracorporeal shock wave lithotripsy (ESWL). Materials and Methods: This meta-analysis was conducted by systematic search for randomized controlled trial (RCT) studies in PubMed/Medline, Scopus, Cochrane Library, Web of Science databases in January 2020, which compared tamsulosin with either placebo or non-placebo control for repeated ESWL. The primary endpoint was stone-free rate (SFR), the second endpoints were stone clearance time and complications. The quality assessment of included studies was performed by using the Cochrane System and Jadad score. Results: 7 RCTs were included in this meta-analysis. Tamsulosin provided higher SFR (for stones larger than 1cm, OR: 5.56, p=0.0003), except for patients with stones less than 1cm. For patients with renal stones (OR: 2.97, p=0.0005) or upper ureteral stones (OR: 3.10, p=0.004), tamsulosin can also provide a higher SFR. In addition, tamsulosin provided a shorter stone clearance time (WMD: −9.40, p=0.03) and lower pain intensity (WMD=-17.01, p <0.0001) and incidences of steinstrasse (OR: 0.37, p=0.0002). Conclusion: Adjunctive MET with tamsulosin is effective in patients with specific stone size or location that received repeated ESWL. However, no well-designed RCT that used computed tomography for the detection and assessment of residual stone fragments was found. More studies with high quality and the comparison between tamsulosin and secondary ESWL are needed in the future.

Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

The effects of single versus combined therapy using LIM-kinase 2 inhibitor and type 5 phosphodiesterase inhibitor on erectile function in a rat model of cavernous nerve injury-induced erectile dysfunction / 亚洲男科学杂志(英文版)

We aimed to determine whether combination of LIM-kinase 2 inhibitor (LIMK2i) and phosphodiesterase type-5 inhibitor (PDE5i) could restore erectile function through suppressing cavernous fibrosis and improving cavernous apoptosis in a rat model of cavernous nerve crush injury (CNCI). Seventy 12-week-old Sprague-Dawley rats were equally distributed into five groups as follows: (1) sham surgery (Group S), (2) CNCI (Group I), (3) CNCI treated with daily intraperitoneal administration of 10.0 mg kg-1 LIMK2i (Group I + L), (4) daily oral administration of 20.0 mg kg-1 udenafil, PDE5i (Group I + U), and (5) combined administration of 10.0 mg kg-1 LIMK2i and 20.0 mg kg-1 udenafil (Group I + L + U). Rats in Groups I + L, I + U, and I + L + U were treated with respective regimens for 2 weeks after CNCI. At 2 weeks after surgery, erectile response was assessed using electrostimulation. Penile tissues were processed for histological studies and western blot. Group I showed lower intracavernous pressure (ICP)/mean arterial pressure (MAP), lower area under the curve (AUC)/MAP, decreased immunohistochemical staining for alpha-smooth muscle (SM) actin, higher apoptotic index, lower SM/collagen ratio, increased phospho-LIMK2-positive fibroblasts, decreased protein kinase B/endothelial nitric oxide synthase (Akt/eNOS) phosphorylation, increased LIMK2/cofilin phosphorylation, and increased protein expression of fibronectin, compared to Group S. In all three treatment groups, erectile responses, protein expression of fibronectin, and SM/collagen ratio were improved. Group I + L + U showed greater improvement in erectile response than Group I + L. SM content and apoptotic index in Groups I + U and I + L + U were improved compared to those in Group I. However, Group I + L did not show a significant improvement in SM content or apoptotic index. The number of phospho-LIMK2-positive fibroblasts was normalized in Groups I + L and I + L + U, but not in Group I + U. Akt/eNOS phosphorylation was improved in Groups I + U and I + L + U, but not in Group I + L. LIMK2/cofilin phosphorylation was improved in Groups I + L and I + L + U, but not in Group I + U. Our data indicate that combined treatment of LIMK2i and PDE5i immediate after CN injury could improve erectile function by improving cavernous apoptosis or eNOS phosphorylation and suppressing cavernous fibrosis. Rectification of Akt/eNOS and LIMK2/cofilin pathways appears to be involved in their improvement.

Síndrome Iridocorneana Endotelial: Relato de Caso da Variante de Chandler / Iridocorneal Endothelial Syndrome: Case Report of Chandler's Variant

Resumo O presente estudo tem por objetivo relatar um raro caso da variante de Chandler da Síndrome Iridocorneana Endotelial em uma paciente de 56 anos. Esta referia baixa acuidade visual em olho direito há 2 anos, acompanhada de fotofobia e prurido. Ao exame oftalmológico, no primeiro atendimento, apresentava em olho direito acuidade visual de conta dedos à 0,5 metro e se observava à biomicroscopia policoria, edema corneano com microcistos e hiperemia conjuntival. O olho esquerdo não apresentava alterações. A pressão intraocular era de 16mmHg no olho direito e 10mmHg no olho esquerdo. Iniciou-se tratamento tópico com dorzolamida, maleato de timolol e dexametasona, sendo então, alcançado o controle da pressão intraocular. Constatou-se no exame de microscopia especular corneana a presença de ice cells. Na biomicroscopia atual, apresenta, no olho acometido, edema corneano com opacidade central, policoria, cristalino não visível e fundo de olho indevassável. Diante da confirmação do diagnóstico de Síndrome de Chandler, pelo quadro clínico compatível e alterações nos exames complementares, a paciente está em acompanhamento no serviço de Oftalmologia do Hospital Federal Servidores do Estado.

Abstract We report in this study a case of Chandler's Syndrome, an Iridocorneal Endhotelial Syndrome variant in a 56 years old patient, female, complaining about low vision in the right side, as well as itching and photophobia in the same side. In the first evaluation, we observed visual acuity of counting fingers at 0,5 meters, corneal swelling with microcystus and conjunctival hyperemia. The left eye was normal. Intraocular pressure was 16mmHg in right eye and 10 mmHg in left eye. We initiated topic treatment with Dorzolamide, Timolol and Dexamethasone, with good control of intraocular pressure. We noticed in corneal specular microscopy the presence of ice cells. In current biomicroscopy it is remarkable the corneal swelling, with central opacity and lens was not visible, as well as the fundoscopy is impossible. We confirmed the diagnosis of Chandler' Syndrome based on the clinical findings, and in abnormalities in complementary exams. Nowadays, the patient is being followed in the Ophthalmology department at Hospital Federal Servidores do Estado.

Treatment of digital ulcers in systemic sclerosis: Case series study of thirteen patients and discussion on outcome / Tratamento de úlceras digitais na esclerose sistêmica: série de casos de 13 doentes e análise crítica dos resultados

Summary Introduction: In systemic sclerosis (SSc), digital ulcers (DU) are debilitating and recurrent. They are markers of prognosis and are associated with disability and mortality. Treatment strategies have been developed to block the proposed mechanisms of this complication. Objective: Clinical description of a population of SSc patients with DU, treatment, complications and outcome. Method: Analysis of 48 SSc patients meeting 2013 ACR-EULAR criteria, followed between 1999-2015; 13 patients had DU. Treatment protocol applied included cycles of 21 days of alprostadil, which can be repeated in the absence of DU healing. After DU healing, bosentan was initiated. Results: DU healing was achieved with intravenous prostanoid in 12 patients; seven patients required repeated treatment for DU healing. Twelve patients were later treated with bosentan; three of them experienced recurrence of DU, while one was anti-B2-GPI positive. Four patients had soft tissue loss and three other suffered digital amputation, these being late diagnosis. Conclusion: Younger patients and early referrals had better outcomes. Endothelin receptor antagonist toxicity should be monitored, particularly in patients previously exposed to hepatotoxic drugs.

Resumo Introdução: As úlceras digitais (UD) são complicações incapacitantes e recorrentes, associadas a menor qualidade de vida e maior mortalidade na esclerose sistêmica (ES). O tratamento baseia-se em antagonizar os mecanismos fisiopatológicos em causa. Objetivo: Descrever uma amostra de doentes com diagnóstico de ES e UD, o tratamento, as complicações e os resultados clínicos. Método: Série de 48 casos diagnosticados com ES, critérios de classificação ACR-EULAR 2013, seguidos entre 1999 e 2015, dos quais 13 apresentavam UD. O protocolo aplicado incluía ciclos de 21 dias de alprostadil podendo ser repetidos no caso de não existir cicatrização. Nos casos em que houve cicatrização foi iniciado bosentano. Resultados: No tratamento das UD, 12 doentes realizaram prostaciclina endovenosa, com necessidade de tratamentos repetidos em sete doentes. Doze doentes foram posteriormente tratados com bosentano, com recorrência de UD em três doentes, um deles com presença de anti-B2-GPI. Quatro doentes ficaram com cicatrizes e em três houve amputação digital, sendo casos de diagnóstico tardio. Conclusão: Os doentes mais jovens tiveram melhores resultados, possivelmente em razão de melhorias globais nos cuidados de saúde prestados e de referenciação precoce. A toxicidade dos antagonistas dos receptores da endotelina deve ser monitorizada, sobretudo em doentes com exposição prévia a drogas hepatotóxicas.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Manifestações oftalmológicas de Síndrome de Klippel Trenaunay / Ophthalmological manifestation of the Klippel Trenaunay Syndrome

RESUMO A Síndrome de Klippel-Trenaunay (SKT) é uma doença congênita rara, com maior prevalência no sexo masculino e incidência de 2-5:100.000. Apresenta-se, na forma clássica, como a tríade de manchas vinho porto, hipertrofia de membros e malformação venosa e/ou linfática. O diagnóstico é essencialmente clínico e devido à complexidade da síndrome, de natureza progressiva e ampla variedade de apresentações clínicas, os pacientes devem ser tratados de forma individualizada por uma equipe multidisciplinar. Alterações oftalmológicas associadas à SKT incluem anormalidades vasculares da órbita, íris, retina, coroide e nervo óptico. Relato de caso: Paciente de 23 anos, sexo feminino, portadora de SKT, em acompanhamento no Centro da Visão - Universidade Federal do Paraná, com queixa de diminuição da acuidade visual em olho direito. A paciente apresentava manchas vinho porto em dimidio direito e hipertrofia de membros ipsilateral. Foi diagnosticado glaucoma e realizados exames complementares oftalmológicos a fim de avaliar o grau de comprometimento dos campos visuais e o fundo de olho. A visão com a melhor correção foi de 20/100 OD e foi de 20/20 OE. À fundoscopia, constatou-se aumento da escavação do nervo óptico à direita - 0,75 x 0,90 mm. Optou-se por tratamento clínico com Cloridrato de Dorzolamida, Latanoprosta, Brimonidina e Timolol, com bons resultados a longo prazo - a tonometria de aplanação mostrou 19 mmHg OD e 15 mmHg OE, apesar da dificuldade na estabilização da doença. Conclusão: Relatos demonstram que os resultados dos tratamentos clínico e cirúrgico do glaucoma em associação à SKT são insatisfatórios quando comparados a outros tipos de glaucoma - o controle clínico não é possível em cerca de 1/3 dos pacientes, e o manejo cirúrgico tem alto índice de complicações. São necessários estudos mais expressivos que estabeleçam a correlação entre glaucoma e SKT e embasem o tratamento de escolha.

ABSTRACT The Klippel-Trenaunay Syndrome (KTS) is a rare congenital disease, which the prevalence is higher in males, and its incidence of 25:100,000. It is presented in its classic form as the triad of port-wine stains, enlarged limbs and venous and / or lymphatic malformation. The diagnosis is essentially clinical and due to the complexity of the syndrome, the progressive characteristic and the wide variety of clinical presentations, a multidisciplinary team should treat patients individually. The ocular changes associated with KTS include vascular, orbit, iris, retina, choroid and optic nerve abnormalities. Case report: A 23-year-old female patient, carrier KTS, being followed at Vision Center - Federal University of Paraná, complaining of decreased visual acuity in the right eye. The patient had port-wine stains in right hemibody and hypertrophy of ipsilateral members. Glaucoma was diagnosed and eye exams were performed to assess the degree of impairment of visual fields and fundus. The best correction was checked at 20/100 OD and 20/20 OS. At fundoscopy, there was increased excavation of the optic nerve right - 0.75 x 0.90 mm. Clinical treatment was chosen with Dorzolamide Hydrochloride, Latanoprost, Brimonidine and Timolol, presenting good long-term results - the tonometry showed 19 mmHg OD and 15 mmHg OS, despite the difficulty in stabilizing the disease. Conclusion: Reports have shown that the results of clinical and surgical treatments of glaucoma in association with KTS are unsatisfactory compared to other types of glaucoma - clinical control is not possible in about 1/ 3 of patients and the surgical management has a high rate of complications. Significant studies are needed to establish the correlation between glaucoma and KTS, and base the treatment of choice.

Prophylactic effects of alpha-blockers, Tamsulosin and Alfuzosin, on postoperative urinary retention in male patients undergoing urologic surgery under spinal anaesthesia

ABSTRACT Purpose Postoperative urinary retention (POUR) is one of the most common complications after surgical procedures under spinal anaesthesia. Recent studies have shown the beneficial effects of alpha-adrenergic blockers in preventing POUR. The aim of this prospective study was to investigate and compare the prophylactic effects of tamsulosin and alfuzosin on POUR after urologic surgical procedures under spinal anaesthesia. Materials and Methods A total of 180 males who underwent elective urologic surgery were included in this study. The patients were randomly allocated into three Groups. The Group I received placebo. Patients in Group II were given 0.4mg of tamsulosin orally 14 and 2 hours before surgery. Patients in Group III were given 10mg of alfuzosin ER orally 10 and 2 hours before surgery. All patients were closely followed for 24 hours postoperatively and their episodes of urinary retentions were recorded. Results There were 60 patients in each Group. Their mean age was 35.95±15.16 years. Fifteen patients in Group I (25%), 3 patients in Group II (5%) and 4 patients in Group III (6.7%) required catheterization because of urinary retention. In tamsulosin group and alfuzosin group, there were a significantly lower proportion of patients with POUR compared with the placebo Group (p=0.002 and p=0.006). The beneficial effects of tamsulosin and alfuzosin on POUR were similar between both Groups (p=0.697). Conclusion This study suggests that the use of prophylactic tamsulosin or alfuzosin can reduce the incidence of urinary retention and the need for catheterization after urologic surgical procedures under spinal anaesthesia.

Efficacy of Tamsulosin, Oxybutynin, and their combination in the control of double-j stent-related lower urinary tract symptoms

ABSTRACT Introduction and objective Indwelling double J ureteral stents are used routinely in the resolution of ureteral obstruction caused by different etiologies. Evaluation of urinary symptoms related to double-J stent, indicate that these affect 73-90% of patients. We conducted a prospective, randomized study, to evaluate the efficacy of tamsulosin, oxybutinin and combination therapy in improving the urinary symptoms. Methods Patients who underwent ureteral stent placement after ureterolithotripsy (total 51), were randomized into three groups: Group I: Tamsulosin 0.4 mg. once per day(17 patients), Group II: Oxybutinin 5 mg. once per day (17 patients), Group III: Tamsulosin+ oxybutynin once per day (17 patients). All the groups received the drugs for three weeks and completed a Spanish validated Ureteral Stent Symptom Questionnaire (USSQ) at day 7 and 21. Results Repeated measures ANOVA showed mean urinary symptom index score was 22.3 vs. 15.5 in group three (p<0.001) at day 7 and 21 respectively. The mean work performance index was 6.6 vs 8.1 (p=0.049) favoring tamsulosin group, the mean sexual score was 0.5 vs 1.5 (p=0.03). Among additional problems the mean was 7.2 vs 6.2 (p=0.03). No significant difference was noted among pain and general health index. No side effects were reported. Conclusions Combination therapy with tamsulosin and oxybutynin improved irritative symptoms and work performance as well as sexual matters. Combination therapy should be considered for patients who complained of stent related symptoms.

Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

ABSTRACT Objective To evaluate the clinical efficiency of alpha1-adrenergic antagonists on stentless ureteroscopic lithotripsy treating uncomplicated lower ureteral stones. Materials and Methods From January 2007 to January 2013, 84 patients who have uncomplicated lower ureteral stones treated by ureteroscopic intracorporeal lithotripsy with the holmium laser were analyzed. The patients were divided into two groups, group A (44 patients received indwelled double-J stents) and group B (40 patients were treated by alpha1-adrenergic antagonists without stents). All cases of group B were treated with alpha1 blocker for 1 week. Results The mean operative time of group A was significantly longer than group B. The incidences of hematuria, flank/abdominal pain, frequency/urgency after surgery were statistically different between both groups. The stone-free rate of each group was 100%. Conclusions The effect of alpha1-adrenergic antagonists is more significant than indwelling stent after ureteroscopic lithotripsy in treating uncomplicated lower ureteral stones.

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. METHODS: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. RESULTS: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. CONCLUSIONS: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis.

Paracoccidioidomycosis treatment / Tratamento da paracoccidioidomicose

SUMMARYConsidered to be an emerging endemic mycosis in Latin America, paracoccidioidomycosis is characterized by a chronic course and involvement of multiple organs in immunocompromised hosts. Infection sequelae are mainly related to pulmonary and adrenal insufficiency. The host-parasite interaction results in different expressions of the immune response depending on parasite pathogenicity, fungal load and genetic characteristics of the host. A few controlled and case series reports have shown that azoles and fast-acting sulfa derivatives are useful treatment alternatives in milder forms of the disease. For moderate/severe cases, more prolonged treatments or even parenteral routes are required especially when there is involvement of the digestive tract mucosa, resulting in poor drug absorption. Although comparative studies have reported that shorter treatment regimens with itraconazole are able to induce cure in chronically-infected patients, there are still treatment challenges such as the need for more controlled studies involving acute cases, the search for new drugs and combinations, and the search for compounds capable of modulating the immune response in severe cases as well as the paradoxical reactions.

RESUMOConsiderada micose endêmica emergente na América Latina, a paracoccidioidomicose é caracterizada por uma evolução crônica e envolvimento de múltiplos órgãos em pacientes com comprometimento imunológico. Sequelas da infecção estão relacionadas principalmente à insuficiência pulmonar e adrenal. A interação hospedeiro-parasito resulta em diferentes expressões da resposta imune dependendo da patogenicidade do parasito, carga fúngica e características genéticas do hospedeiro. Alguns estudos controlados e séries de casos têm demonstrado que azóis de ação rápida e derivados de sulfa constituem alternativas terapêuticas úteis nas formas mais leves da doença. Para casos moderados/graves, tratamentos mais prolongados ou mesmo por via parenteral são necessários especialmente quando há envolvimento de mucosa do trato digestivo, resultando em absorção deficiente de drogas. Embora estudos comparativos tenham relatado que esquemas terapêuticos mais curtos com itraconazol sejam capazes de induzir cura em pacientes cronicamente infectados, ainda existem desafios no tratamento, tais como a necessidade de maior número de estudos controlados envolvendo casos agudos, busca por novas drogas e combinações, compostos capazes de modular a resposta imune nos casos graves, e reações paradoxais.

Effects of PDE type 5 inhibitors on Left Ventricular Diastolic Dysfunction in Resistant Hypertension / Efeitos dos Inibidores da PDE do Tipo 5 sobre a Disfunção Diastólica Ventricular Esquerda na Hipertensão Arterial Resistente

Resistant hypertension (RHTN) is a multifactorial disease characterized by blood pressure (BP) levels above goal (140/90 mmHg) in spite of the concurrent use of three or more antihypertensive drugs of different classes. Moreover, it is well known that RHTN subjects have high prevalence of left ventricular diastolic dysfunction (LVDD), which leads to increased risk of heart failure progression. This review gathers data from studies evaluating the effects of phosphodiesterase-5 (PDE-5) inhibitors (administration of acute sildenafil and short-term tadalafil) on diastolic function, biochemical and hemodynamic parameters in patients with RHTN. Acute study with sildenafil treatment found that inhibition of PDE-5 improved hemodynamic parameters and diastolic relaxation. In addition, short-term study with the use of tadalafil demonstrated improvement of LVDD, cGMP and BNP-32 levels, regardless of BP reduction. No endothelial function changes were observed in the studies. The findings of acute and short-term studies revealed potential therapeutic effects of IPDE-5 drugs on LVDD in RHTN patients.

A Hipertensão arterial resistente (HAR) é uma doença multifatorial caracterizada por níveis pressóricos acima das metas (140/90 mmHg), a despeito de tratamento farmacológico otimizado de 3 ou mais fármacos anti-hipertensivos de diferentes classes. Pacientes diagnosticados como hipertensos resistentes apresentam alta prevalência de disfunção diastólica do ventrículo esquerdo (DDVE) que proporciona risco aumentado para insuficiência cardíaca. Esta revisão reúne dados de estudos prévios avaliando os efeitos dos inibidores de fosfodiesterase-5 (PDE-5) (administração aguda de sildenafil e de curto prazo de tadalafil) na função diastólica e nos parâmetros bioquímicos e hemodinâmicos em pacientes com HAR. O estudo agudo com sildenafil demonstrou que a inibição da PDE-5 melhorou os parâmetros hemodinâmicos e de relaxamento diastólico. Além disso, o estudo curto prazo com o uso de tadalafil revelou melhora da DDVE e dos níveis de GMPc e BNP-32, independente de redução de pressão arterial. A função endotelial não apresentou alteração com ambos os tratamentos. Os resultados dos estudos agudo e de curto prazo sugerem efeitos terapêuticos potenciais dos fármacos inibidores da PDE-5 na disfunção diastólica em pacientes com HAR.

Distribution of ureteral stones and factors affecting their location and expulsion in patients with renal colic

PURPOSE: To evaluate the distribution of ureteral stones and to determine their characteristics and expulsion rate based on their location. MATERIALS AND METHODS: We retrospectively reviewed computed tomography (CT) findings of 246 patients who visited our Emergency Department (ED) for renal colic caused by unilateral ureteral stones between January 2013 and April 2014. Histograms were constructed to plot the distribution of stones based on initial CT findings. Data from 144 of the 246 patients who underwent medical expulsive therapy (MET) for 2 weeks were analyzed to evaluate the factors responsible for the stone distribution and expulsion. RESULTS: The upper ureter and ureterovesical junction (UVJ) were 2 peak locations at which stones initially lodged. Stones lodged at the upper ureter and ureteropelvic junction (group A) had a larger longitudinal diameter (4.21 mm vs. 3.56 mm, p=0.004) compared to those lodged at the lower ureter and UVJ (group B). The expulsion rate was 75.6% and 94.9% in groups A and B, respectively. There was no significant difference in the time interval from initiation of renal colic to arrival at the ED between groups A and B (p=0.422). Stone diameter was a significant predictor of MET failure (odds ratio [OR], 1.795; p=0.005) but the initial stone location was not (OR, 0.299; p=0.082). CONCLUSIONS: The upper ureter and UVJ are 2 peak sites at which stones lodge. For stone size 10 mm or less, initial stone lodge site is not a significant predictor of MET failure in patients who have no previous history of active stone treatment in the ureter.

Optic neuritis complicating herpes zoster ophthalmicus in an immunocompetent patient / Zoster optic neuritis in immunocompentent

A 58-year-old woman presented with rash over the left side of the face and intense acute uveitis. Following careful review of the symptoms and dilated fundus examination unilateral optic neuritis was discovered. The rash was typical of varicella zoster dermatitis. Patients presenting with herpes zoster ophthalmicus should always undergo dilated fundus examination, as there is a potential risk of unexpected posterior segment inflammation. Early diagnosis and prompt treatment can avoid visual sequelae.

Paciente de 58 anos de idade apresentando erupção cutânea no lado esquerdo da face e intensa uveíte unilateral. Após cuidadosa revisão dos sintomas e exame de fundo do olho foi detectada neurite óptica. O rash era típico de dermatite por varicella zoster. Pacientes apresentando quadro de herpes zoster oftálmico devem ser submetidos ao exame de fundo do olho devido ao risco de inesperada inflamação do segmento posterior. Diagnóstico precoce e tratamento imediato podem evitar danos visuais.

Treatment of Bartter syndrome. Unsolved issue, / Tratamento da síndrome de Bartter. Problema não resolvido,

Objective: To describe the results of a long-term follow-up of Bartter syndrome patients treated with different drugs. Method: Patients were diagnosed according to clinical and laboratory data. Treatment protocol was potassium supplementation, sodium, spironolactone, and non-steroidal anti-inflammatory drug. Patients who developed proteinuria were converted to angiotensin conversion enzyme inhibitor. The variables evaluated for each drug were Z-score for weight and stature, proteinuria, creatinine clearance, gastrointestinal complaints, amount of potassium supplementation, serum potassium and bicarbonate levels, and findings of upper digestive endoscopy. Results: 20 patients were included. Follow-up was 10.1 ± 5.2 years. 17 patients received indomethacin for 5.9 ± 5.3 years; 19 received celecoxib, median of 35 months; and five received enalapril, median of 23 months. During indomethacin, a statistically significant increase was observed in the Z-score for stature and weight, without a change in the creatinine clearance. Seven of 17 patients had gastrointestinal symptoms, and upper digestive endoscopy evidenced gastritis in three patients and gastric ulcer in four patients. During celecoxib use, a significant increase was detected in the Z-score for stature and weight and a reduction of hyperfiltration; seven patients presented gastrointestinal symptoms, and upper digestive endoscopy evidenced mild gastritis in three. During enalapril use, no significant changes were observed in the Z-score for stature, weight and creatinine clearance. The conversion to enalapril resulted in a significant reduction in proteinuria. Conclusion: The authors suggest starting the treatment with celecoxib, and replacing by ACEi if necessary, monitoring the renal function. The safety and efficacy of celecoxib need to be assessed in larger controlled studies. .

Objetivo: Descrever os resultados de um acompanhamento de longo prazo de pacientes com síndrome de Bartter tratados com diferentes medicamentos. Método: Pacientes diagnosticados segundo os dados clínicos e laboratoriais. Protocolo de tratamento: suplementação de potássio, sódio, espironolactona e medicamento anti-inflamatório não esteroidal. Os pacientes que desenvolveram proteinúria foram submetidos a inibidor da enzima de conversão da angiotensina. As variáveis avaliadas durante o uso de cada medicamento foram: escore Z para peso e estatura, proteinúria, depuração da creatinina, queixas gastrointestinais, quantidade da suplementação de potássio, níveis séricos de potássio e bicarbonato e achados da endoscopia digestiva alta. Resultados: Foram incluídos 20 pacientes. O acompanhamento foi de 10,1 ± 5,2 anos. No total, 17 pacientes receberam indometacina por 5,9 ± 5,3 anos, 19 receberam celecoxib por aproximadamente 35 meses e cinco receberam enalapril por aproximadamente 23 meses. Durante o uso de indometacina, observamos um aumento estatístico significativo no escore Z para estatura e peso, sem alteração na depuração da creatinina. 7/17 pacientes apresentaram sintomas gastrointestinais, e a endoscopia digestiva alta mostrou gastrite em três pacientes e úlcera gástrica em quatro. Durante o uso de celecoxib, detectamos um aumento significativo no escore Z para estatura e peso e uma redução da hiperfiltração; sete pacientes apresentaram sintomas gastrointestinais e a endoscopia digestiva alta mostrou gastrite leve em três pacientes. Durante o uso de enalapril, não observamos alterações significativas no escore Z para estatura, peso e depuração da creatinina. A mudança da medicação para enalapril resultou em uma ...

Effects of prostatic inflammation on LUTS and alpha blocker treatment outcomes

Purpose To evaluate the association between prostatic inflammation and lower urinary tract symptoms (LUTS), and to identify the effects of prostatic inflammation on the treatment with an alpha blocker. Materials and Methods 111 Participants who were aged ≥ 50 years, the presence of LUTS (maximal flow rate < 20 m/s, IPSS ≥ 11), and an elevated PSA level (3-20ng/mL) were treated with tamsulosin 0.2mg once daily for 3 months after prostate biopsies. Prostatic inflammation was scored as none (0), mild (I), moderate (II), or marked (III). LUTS parameters including urine flow rates, IPSS, PSA, and prostate volume were evaluated. Results Inflammation grading resulted in 25, 60, and 26 patients that were grade 0, I, and II, respectively. Lower grade inflammation was related to higher urine flow rate at baseline. Patients with higher inflammation grades had larger prostate volumes, larger total and transitional zone volumes, and higher PSA levels. Overall, urine flow rates and residual urine volume were improved after 3 months of alpha blocker therapy. Eighty percent of patients with grade 0 inflammation, 73% of patients with grade I inflammation, and 92.3% of patients with grade II inflammation showed improvement of LUTS after treatment. Longer duration of treatment was related to a decreased chance of improvement of LUTS. Patients with increased IPSS voiding subscales could be predictive of improvement of LUTS. Conclusions Patients with high grade inflammation had lower flow rates and higher prostatic volumes than patients with low grade inflammation. Inflammation grade did not affect the outcomes of alpha blocker treatment. .