Interaction Between Determinants Governing Urine Volume in Patients With ADPKD on Tolvaptan and its Impact on Quality of Life.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic cause of kidney failure. Tolvaptan, a vasopressin 2 receptor antagonist, is the first drug with proven disease-modifying activity. Long-term treatment adherence is crucial, but a considerable fraction of patients discontinue treatment, because of aquaretic side effects. Methods: Twenty-four-hour urine was collected in 75 patients with ADPKD during up-titration of tolvaptan and, in combination with clinical characteristics, examined to identify factors influencing urine volume. Patient-reported outcomes were analyzed using the Short Form-12 (SF-12) and patient-reported outcomes questionnaires reporting micturition frequency and burden of urine volume. Results: Initiation of therapy led to a large increase in urine volume followed by only minor further increase during up-dosing. Younger patients and patients with better kidney function experienced a larger relative rise. Twenty-four-hour urine osmolality dropped by about 50% after therapy initiation independently of dose, with a considerable proportion of patients achieving adequate suppression. Sodium and potassium intake turned out to be the only significant modifiable factors for urine volume after multivariate linear regression models, whereas age and weight could be identified as non-modifiable factors. No change in quality of life (QoL) was detected in relation to treatment or urine volume using SF-12 questionnaires, a finding that was further supported by the results of the patient-reported outcomes assessment. Conclusion: This study provides an in-detail analysis of factors associated with the degree of polyuria on tolvaptan and puts them into the context of QoL. These findings will contribute to optimized patient counseling regarding this treatment option in ADPKD.

A Low-Cost Sequencing Platform for Rapid Genotyping in ADPKD and its Impact on Clinical Care.

Introduction: Autosomal-dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Because of the heterogeneity in disease progression in ADPKD, parameters predicting future outcome are important. The disease-causing genetic variant is one of these parameters. Methods: A multiplex polymerase chain reaction (PCR)-based panel (MPP) was established for analysis of 6 polycystic kidney disease (PKD) genes (PKD1, PKD2, HNF1B, GANAB, DZIP1L, and PKHD1) in 441 patients with ADPKD. Selected patients were additionally sequenced using Sanger sequencing or a custom enrichment-based gene panel. Results were combined with clinical characteristics to assess the impact of genetic data on clinical decision-making. Variants of unclear significance (VUS) were considered diagnostic based on a classic ADPKD clinical phenotype. Results: Using the MPP, disease-causing variants were detected in 65.3% of patients. Sanger sequencing and the custom gene panel in 32 patients who were MPP-negative revealed 20 variants missed by MPP, (estimated overall false negative rate 24.6%, false-positive rate 9.4%). Combining clinical and genetic data revealed that knowledge of the genotype could have impacted the treatment decision in 8.2% of patients with a molecular genetic diagnosis. Sequencing only the PKD1 pseudogene homologous region in MPP-negative patients resulted in an acceptable false-negative rate of 3.28%. Conclusion: The MPP yields rapid genotype information at lower costs and allows for simple extension of the panel for new disease genes. Additional sequencing of the PKD1 pseudogene homologous region is required in negative cases. Access to genotype information even in settings with limited resources is important to allow for optimal patient counseling in ADPKD.

Tratamento cirúrgico de pseudoaneurisma de artéria isquiática: relato de caso e revisão da literatura / Surgical treatment of false aneurysm of the sciatic artery: case report and literature review

A persistência da artéria isquiática é uma rara variação anatômica, com poucos casos descritos na literatura, manifestando-se por formação de aneurisma, massa pulsátil em glúteo, isquemia aguda ou crônica de membro inferior e compressão de nervo isquiático. O diagnóstico é confirmado com exames de imagem: mapeamento duplex, angiotomografia e angiorressonância magnética. O tratamento é indicado nos casos sintomáticos ou quando há formação de aneurisma, realizado através de ligadura ou embolização por via endovascular, sendo necessário a revascularização do membro nos casos em que a artéria isquiática é a principal responsável pelo suprimento sangüíneo do membro. Apresentamos o caso de uma paciente do sexo feminino, 43 anos, com pseudoaneurisma de artéria isquiática confirmada por mapeamento duplex e angiorressonância magnética, com quadro de neuropatia isquiática por compressão nervosa e dor local. A paciente foi submetida à exploração cirúrgica com ligadura da artéria isquiática e remoção dos trombos. No seguimento de 12 meses, apresentou importante melhora da dor e realizou fisioterapia motora para recuperação das funções neurológicas do membro.

The persistent sciatic artery is a rare anatomical variation, with few cases described on the literature. It presents clinically as aneurysm formation, pulsate gluteal mass, acute or chronic limb ischemia and sciatic nerve compression. Diagnosis is confirmed by imaging methods: duplex scan, CT angiographt and magnetic resonance angiography. Treatment is indicated in symptomatic cases and when there is aneurysm formation and it is performed by ligation of the sciatic artery or endovascular embolization, associated with limb revascularization in the cases the sciatic artery is the main blood supply to the limb. We report the case of a 43 year-old female patient, ,with a false aneurysm of the sciatic artery confirmed by duplex scan and magnetic resonance angiography who had local pain and sciatic neuropathy due to neural compression. Surgical exploration was performed, with ligation of sciatic artery and thrombus removal. At the 12 months follow up there was significant pain relief and she was performing motor physical therapy to recover the neurological functions of the limb.

Manejo da gangrena de Fournier: experiência de um hospital universitário de Curitiba / Management of Fournier's gangrene: experience of a university hospital of Curitiba

OBJETIVO: Analisar os resultados obtidos no Serviço de Cirurgia Geral do Hospital Universitário Cajuru - PUCPR, com o tratamento da gangrena de Fournier. MÉTODOS: Foram revisados os prontuários de 40 pacientes com diagnóstico de Gangrena de Fournier internados no hospital universitário Cajuru de Novembro de 1999 a Abril de 2006, analisando-se as variáveis: sexo, idade, fatores predisponentes, etiologia, localização da lesão, exames laboratoriais, procedimentos cirúrgicos realizados, antibioticoterapia e utilização de câmara hiperbárica. RESULTADOS: A etiologia mais comum foi de origem anorretal. O agente etiológico mais prevalente foi a E. coli. O fator predisponente predominantes foi a diabetes mellitus, A maioria dos pacientes eram do sexo masculino. A localização e extensão da lesão mais freqüente foi a perineal. Todos foram submetidos à desbridamento cirúrgico, 17 à colostomia e dois à cistostomia. Todos os pacientes utilizaram antibiótico, sendo os mais usados: metronidazol e gentamicina. Vinte e seis pacientes submeteram-se à terapia hiperbárica. A mortalidade global foi de 20%. CONCLUSÃO: A Síndrome de Fournier, apesar de todos os avanços terapêuticos atuais, continua apresentando altos índices de mortalidade. O reconhecimento precoce da infecção associado a tratamento agressivo e invasivo são medidas essenciais para se tentar diminuir esses índices prognósticos.

OBJECTIVE: To analyze the results obtained in the Department of General Surgery, Cajuru University Hospital - PUCPR, with the treatment of Fournier's gangrene. METHODS: We reviewed the charts of 40 patients diagnosed with Fournier's gangrene admitted to the Cajuru University Hospital from November 1999 to April 2006, analyzing gender, age, predisposing factors, etiology, lesion location, laboratory tests , surgical procedures, antibiotic use and hyperbaric oxygen therapy. RESULTS: The most common etiology was the anorectal origin. The most prevalent etiological agent was E. coli. The predominant predisposing factor was diabetes mellitus. The majority of patients were male. The location and extent of injury was usually in the perineum. All underwent surgical debridement, 17 with associated colostomy and two with combined cystostomy. All patients received antibiotics, the most used being metronidazole and gentamicin. Twenty-six patients underwent hyperbaric therapy. The overall mortality was 20%. CONCLUSION: Fournier's syndrome, despite all the advances in treatment today, continues to show high mortality rates. Early recognition of infection associated with invasive and aggressive treatment are essential for attempting to reduce these prognostic indices.

Management of Fournier's gangrene: experience of a university hospital of Curitiba.

OBJECTIVE: To analyze the results obtained in the Department of General Surgery, Cajuru University Hospital-PUCPR, with the treatment of Fournier's gangrene. METHODS: We reviewed the charts of 40 patients diagnosed with Fournier's gangrene admitted to the Cajuru University Hospital from November 1999 to April 2006, analyzing gender, age, predisposing factors, etiology, lesion location, laboratory tests, surgical procedures, antibiotic use and hyperbaric oxygen therapy. RESULTS: The most common etiology was the anorectal origin. The most prevalent etiological agent was E. coli. The predominant predisposing factor was diabetes mellitus. The majority of patients were male. The location and extent of injury was usually in the perineum. All underwent surgical debridement, 17 with associated colostomy and two with combined cystostomy. All patients received antibiotics, the most used being metronidazole and gentamicin. Twenty-six patients underwent hyperbaric therapy. The overall mortality was 20%. CONCLUSION: Fournier's syndrome, despite all the advances in treatment today, continues to show high mortality rates. Early recognition of infection associated with invasive and aggressive treatment are essential for attempting to reduce these prognostic indices.

Síndrome de Lemierre: relato de caso / Lemierre syndrome: case report

A síndrome de Lemierre é uma doença rara, mais comum em jovens, causada frequentemente pelo Fusobacterium necrophorum. Inicia-se com faringite e propaga-se até a veia jugular interna, promovendo uma fonte de bacteremia contínua e êmbolos sépticos pulmonares. Manifestações clínicas incluem febre, alterações respiratórias e massa cervical. O diagnóstico é realizado por tomografia computadorizada e duplex scan, além de hemocultura ou cultura direta. O tratamento é realizado com antibióticos beta-lactâmicos resistentes a beta-lactamases, sendo a cirurgia raramente necessária. Paciente do sexo feminino, 34 anos, com quadro de orofaringite, evoluiu em 48 horas com queda do estado geral, febre, aumento de volume e dor em região cervical esquerda...

Lemierre syndrome is a rare disease. It often affects young adults and is most frequently caused by Fusobacterium necrophorum. The initial event is pharyngitis, which extends to the internal jugular vein, serving as source of continuous bacteremia and septic pulmonary emboli. Clinical manifestations include fever, respiratory distress, and swollen cervical lymph nodes. Diagnosis is established based on blood culture or direct blood culture and confirmed by computed tomography and/or duplex scan. Treatment consists of administration of beta-lactamase resistant beta-lactam antibiotics...