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CLINICS is a multidisciplinary medical journal. This editorial highlights the field of cardiovascular research. We have selected papers published from 2011-2012 and focused on the concept of Continuously Variable Rating, which we have recently introduced as an alternative and hopefully superior method for evaluating published scientific papers (1).

In this issue of CLINICS, we open a new section entitled “Bringing Ideas Together” in which experienced authors will contribute a measure of speculative thought on apparently unrelated themes in medical practice. This section will only occur when a sufficiently interesting article is offered to us. In this issue, a paper by Pereira et al. on the imbalance between thyroid hormones and the dopaminergic system as possible central central factors in the pathophysiology of restless legs syndrome is offered for discussion. Comments, letters and editorials are welcome, subject of course to peer evaluation. In this issue we publish ten original clinical science papers, one review and three case reports. Otsuki et al. note that proprietary sevoflurane is diluted in water, whereas a generic sevoflurane (Sevocris) is produced with propylene glycol as a stabilizing additive. They investigated whether the original and generic sevoflurane preparations differed in terms of their minimum alveolar concentration values and hemodynamic effects in aporcine experimental model: their results indicate that the propylene glycol added sevoflurane can be used as safely as the water diluted sevoflurane, regarding hemodynamic and pulmonary effects. Senne et al. assessed the influence of Nd: YAG laser unilateral posterior capsulotomy on visual acuity and perception of difficulties with vision-related daily life activities through an interventional survey with 48 patients aged between 40 and 80 years, with uni- or bilateral pseudophakia, posterior capsule opacification and visual acuity equal to or less than 0.30 (logMAR) in one eye. All the patients were submitted to posterior capsulotomy by Neodymium: Yttrium-Aluminium-Garnet (Nd: YAG) laser, resulting in a significant improvement of visual acuity in the capsulotomized eye and, according to the subjects’ perception, a reduction of difficulty in most vision-dependent daily activities. Heldwein et al. endeavored to identify the most cited articles in general surgery published by Brazilian authors between 1970 and 2010, over which the Brazilian output of surgical research increased 21-fold. Out of 1,713 articles, they identified 9 classics (more than 100 citations received), the majority of which were the result of international cooperation. Takara et al. compared the measurements of spirometric peak expiratory flow (PEF) from five different PEF meters and to determine whether their values are in agreement. Comparisons were performed in 68 healthy, sedentary and insufficiently active subjects, aged from 19 to 40 years old, using Air Zone®, Assess®, Galemed®, Personal Best® and Vitalograph® peak flow meters. No agreement was found between the spirometric values and the five PEF meters. The results suggest that Galemed® recorded values may have possibly underestimated true values and thereby leading to an intervention that, in fact, would not be necessary, while Air Zone® meter values may have been overestimates covering up the need for intervention. They indicate that these points must be taken into account when interpreting the readings from both devices for younger people. Theey also stress the attention required when directly comparing different types of PEF meters recorded values. Kargili et al. note that the association between polycystic ovarian syndrome and increased cardiovascular disease risk is still a controversial issue. Consequently they conducted a study to determine whether there is a relationship between sleep blood pressure pattern disturbances and polycystic ovarian syndrome in 168 young women aged 26±5 years. Authors found that a non-dipping blood pressure pattern has a high prevalence in polycystic ovarian syndrome patients even if they are young and non-obese. Lin et al. examined risks, rates of readmission and their predictors 14 days, one year, and five years after discharge for the psychiatric population in Taiwan through a claim data-based prospective study with 44,237 first-time hospitalized psychiatric patients discharged in 2000, and followed for up to 5 years of discharge. Cumulative incidence (CI) and incidence density (ID) of readmission were calculated for various follow-up periods after discharge; and Cox-proportional hazard models were conducted to identify the significant predictors. They found that significant predictors for psychiatric readmission in 14 days to 5 years after discharge were essentially the same (male gender, length of hospital stay >15 days, economically poor) except patient’s age and hospital accreditation level. This study also highlighted the importance of socioeconomic factors in the prediction of readmission. In contrast young adults (20–39 years) were significantly associated with increased risks of

Although peer review has been used to maintain the quality of published research, it can be a “seriously flawed” process1 and might result in the publication of papers with errors. I refer here to the report2 of a de novo (2;16)(q36.3;p13.3) translocation that is associated with Rubinstein-Taybi syndrome (RTS). This report was published in Clinics and contains a cytogenetic mistake in the depicted karyotype. Although the translocation is correct (2;16), the chromosome 2 breakpoint is juxtaposed to the centromere and not at 2q36.3. Thus, the telocentric der (2) is composed of the whole 2q (including the centromere) and is presumably capped with the 16p telomere whereas the whole 2p is attached to 16p13.3. Therefore, the correct karyotype should be written as 46,XX,t(2;16)(p11.2;p13.3)dn. In addition, the assertion by Torres et al.2 that their “RTS patient is the third reported case with a de novo t(2;16)(q36.3;p13.3)” is groundless because only one RTS patient with this translocation has been reported.3 In a subsequent paper, Torres et al.4 have repeated the same cytogenetic error. These remarks further stress that even serious mistakes may be unnoticed during the peer and editorial review process.

OBJECTIVES: The objective of this paper was to characterize the population seen at the dentistry unit of the hematology-oncology service of the Oncology-Hematology Service, Instituto da Crianca at the Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo. Oral problems resulting from cancer therapy increase the risk of infection, length of hospital stay, treatment cost and negative impact on the course and prognosis of the disease. METHOD: Of the 367 medical records of cancer patients seen from November 2007 until December 2008: 186 with a cancer diagnosis and complete clinical data were selected, while 20 with a cancer diagnosis and incomplete records were excluded; 161 medical records with only hematological diagnosis were also excluded. The following characteristics were assessed: ethnicity, gender, age, diagnosis and characteristics of the neoplasm, cancer therapy status and performed dental procedures. RESULTS: Review of 1,236 visits indicated that 54% (n=100) of the patients had blood cancers, 46% (n=86) had solid tumors and 63% were undergoing anticancer therapy. The proportion of males (52.7%) in the study population was slightly greater. The most common cancer was acute lymphocytic leukemia (32.2%). Cancer occurred more often among those patients aged 5 to 9 years. The most common dental procedures were restorative treatment, preventive treatment and removal of infectious foci. CONCLUSION: The characteristics of the studied population were similar to those of the general Brazilian and global populations, especially regarding gender and diagnosis distributions. The aim of implementation of the dentistry unit was to maintain good oral health and patients' quality of life, which is critical to provide oral care and prevent future oral problems.

Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis caused by the fungus Paracoccidioides brasiliensis. Also known as South American blastomycosis and Lutz‐Splendore‐Almeida disease, PCM is endemic in South and Central America, especially in Brazil, Venezuela, Colombia, Ecuador, and Argentina.1 Its chronic form, which accounts for more than 80% of cases, usually affects men between 29 and 60 years old—predominantly rural workers—and it is characterized by polymorphic lesions that may affect any organ, in particular the skin; the lymph nodes; the lungs; the oral, nasal, and gastrointestinal mucosa; the adrenals; and the central nervous system.1 The genitourinary tract is the least commonly involved system in chronic PCM. In the present paper, we describe two cases of genitourinary PCM located in the penis and the prostate that were treated at our institution, and we review the pertinent literature.

As teachers of medical courses and professionals who work in a challenging environment for public health and day-to-day clinical decisions, we are concerned about how up-to-date medical knowledge that is presented in scientific papers is translated into clinical directives or public health decisions. To illustrate, we refer to screening for breast, colon and prostate cancer. The common message that may be derived from these examples was summed in The New York Times in 2007 (1), as follows: “Nobody likes to be at the mercy of an expert, especially of those who charge for their services and whose trustworthiness can be hard to assess. Mechanics are a common source of this frustration, but there are many others: doctors, plumbers, financial advisers, real estate agents and technical support people, to name a few.”

The advent of liver transplantation provided a treatment option for several pediatric terminal liver diseases. In September 1989, we performed the first pediatric liver transplantation in a child with biliary atresia at the Instituto da Crianca do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo after an extensive program of basic science and animal training. Thanks to institutional efforts and the dedication of a multi-disciplinary team composed of doctors, nurses, hospital administrators, pharmacists, physiotherapists, nutritionists, social workers and psychologists, it was possible for us to create and maintain a Brazilian pediatric liver transplantation program that is comparable to those of the world's best centers. From 1989 to the present, we have performed 680 liver transplantations in children with different terminal liver diseases, including the most severe cases of fulminant hepatic failure. However, the scarcity of suitable deceased donors has been a great problem for all liver transplantation programs, particularly in the pediatric area because the need to reduce the volume of liver grafts and the relative severity of the clinical conditions of our patients make the procurement of deceased donors even more difficult and selective. The positions of liver recipient candidates on the waiting list (a single list for adults and children) were based on chronologic criteria until June of 2006 and the mean time from inclusion on the list until transplantation was three years. Consequently, waiting-list mortality (affecting more than 50% of patients) was an important problem that had yet to be solved. From that time until the present, despite the introduction of the Pediatric End-stage Liver Disease (PELD)/Model for End-stage Liver Disease (MELD) criteria for the inclusion and classification of patients based on the severity of their hepatic disease and clinical conditions, the waiting-list mortality rate has remained persistently high. In this context, we began a program of living donor transplantation and the first procedure was performed in 1998. To date, careful selection and preparation of potential living donors have allowed us to perform 280 procedures, with a low morbidity rate and no donor complications or deaths 1. Resection of the left lateral segment or the left lobe (which provides sufficient liver mass for pediatric recipients) is a procedure that is relatively safe for the donors 2. Our center's surgical team includes only pediatric surgeons, with extensive experience in pediatric liver surgery and liver transplantation, including experience with adolescents, which allows us to perform the donor hepatectomies without the participation of adult surgeons. We emphasize that the donor and recipient procedures are performed in adjoining rooms, with full synchronization, in an exclusively pediatric hospital that has undergone logistical and structural adjustments to allow for the procedures in the adults to be performed safely and comfortably. Additionally, in the early postoperative period, the donor (in general, a mother or father) and the recipient can stay together in the same hospital. Finally, another advantage is that the team of pediatric surgeons can perform adequate early and late follow-ups of all donors. Regarding the benefits of living donor transplantation for the recipients, the advantages of good-quality grafts outweigh the technical difficulties related to the smaller caliber of the vascular anastomoses and to biliary reconstruction 3. Thus, despite the introduction of MELD and PELD scores to determine waiting-list positions, living donor liver transplantation maintains a crucial role in our program because children can be treated earlier and receive extensively evaluated grafts with optimal function that have been exposed to minimal cold ischemia. However, liver transplantation is a complex procedure, and as such, it is still associated with several postoperative complications. Surgical complications may involve the vascular (hepatic artery, portal vein and hepatic vein) and biliary structures. In this context, we introduced the utilization of simplified arterial microsuture techniques, which make the performance of arterial anastomoses much easier and more practical 4 and the precise utilization of arterial grafts 5, which allows for progressively better results in terms of arterial complications. Moreover, the utilization of a Rex shunt (i.e., a bypass between the superior mesenteric vein and the portal vein left branch) in cases of portal thrombosis 6 and technical modification of the hepatic vein anastomosis procedure, which involves the creation of a wide opening in the anterior wall of the inferior vena cava 7, have been responsible for a decrease in the rate of venous complications. However, biliary complications and size mismatches remain unsolved problems and are thus the subjects of important experimental studies. A weaning rat model of selective biliary obstruction was developed in our laboratory, with the aim of improving our understanding of biliary cirrhosis in cases of intrahepatic segmental biliary stenosis 8,9. Moreover, the consequences of engrafting liver grafts that are disproportionately large relative to the recipients' size, i.e., cases of infant recipients who are less than 5 kg in size, have not been completely elucidated. Therefore, we created a new swine “large-for-size” liver transplantation model 10 and many studies that have tentatively clarified the molecular and flowmetric mechanisms of lesions in this situation 11 as well as therapeutic measures to attenuate such lesions have been reported 11. Finally, the immunologic mechanisms involved in the humoral and cellular rejection of solid organ transplants remain a matter of continuing research in the literature. Despite all of the advances in immunosuppressive regimens and the development of accurate drugs with fewer collateral effects, acute and chronic rejections remain dreaded complications of pediatric liver transplantation. The diagnoses of acute and chronic rejection are based on histopathological findings, and portal inflammation and centrilobular necrosis are characteristics of acute rejection. Moreover, biliary duct paucity in the portal space and foam cell arteriopathy are the main aspects of chronic rejection 12. Regarding acute cellular rejection, treatment and management are relatively standardized and most cases exhibit good responses to corticosteroid bolus treatments as well as tacrolimus level adjustment 13. The treatment and evolution of pediatric patients with chronic rejection are not well characterized, as few published studies are present in the literature. Indeed, the mechanisms of chronic rejection are not completely known and the progressive biliary duct paucity may not respond to increased immunosuppression, which can lead to severe liver dysfunction, a need for retransplantation or death, as discussed in the paper by Tannuri et al. in the current issue of Clinics. Finally, the early histological findings and histological aspects that are suggestive of irreversibility must be defined, and prognostic factors after chronic rejection is diagnosed must be identified, although certain investigations have previously tried to identify the risk factors for the development of chronic rejection following liver transplantation in pediatric 14 and adult 15,16 populations. In conclusion, liver transplantation is a relatively new procedure that allows for the survival of many infants and children who otherwise would die. However, this procedure also results in a number of conditions and complications that have never been previously recognized and treated. Therefore, much remains to be studied and accomplished, particularly in the field of immunology.

Cerebral sparganosis is a rare parasitic disease of thecentral nervous system that is caused by sparganum.Cerebral sparganosis occurs worldwide, but it is foundmore frequently in China, Japan, and Southeastern Asia (1-2). Sparganum, the second-stage larva of Spirometra mansoni,can produce chronic active inflammation through slowmigration in the brain (1). They can also parasitize othersites of the human body, such as the subcutaneous tissue,body cavities and eyes, and survive for 5-20 years (3).In this paper, we report a case of cerebral sparganosis,including the magnetic resonance imaging (MRI) character-istics of local migration and the surgical finding of a liveworm. A new pathological finding, a tunnel-like structure,was observed and most likely represented a sparganummigration path.

A review of the literature shows that we owe the first medical description of a child with Down syndrome to Jean-Etienne Dominique Esquirol in 1838. It would be 28 years until John L. Down published a paper accurately describing the characteristics of this syndrome, which is therefore named after him.1 In 1959, Lejeune and Jacobs independently determined that Down syndrome was linked to trisomy 21.2 At the time of publication, Down syndrome is the most common chromosomal abnormality, causing intellectual disability with intelligence quotients (IQs) in the range of 20–85.3 In general terms, there is no racial predilection, the male to female ratio is approximately 1.15∶1, and it occurs in approximately 1 in 500 to 1 in 1000 live births.3,4 Furthermore, Down syndrome may present considerable challenges, as manifestations may be quite diverse and involve many organ systems, which may be related to the cases of sudden death occurring in this group.3 Moreover, we must point out that other diseases underlying Down syndrome may be directly associated with the fatal episodes observed in these individuals. Epilepsy occupies an interesting role in this scenario. To better understand this new paradigm, some hypotheses must be put forward. Epilepsy is one of the most common serious brain disorders. Worldwide, epilepsy is estimated to affect 50 million people, most of whom live in developing countries and therefore may have limited access to medical treatment.5,6 Unfortunately, epilepsy is associated with a two- to three-fold increase in mortality compared with the general population, and sudden unexpected death is the most important direct epilepsy-related cause of death.7 In general terms, sudden unexpected death in epilepsy is responsible for 7.5% to 17% of all deaths in epilepsy and has an incidence among adults between 1∶500 and 1∶1,000 patient-years.8 The major risk factor for sudden unexpected death in epilepsy is chronic, uncontrolled epilepsy9,10. In addition, the major domain of potential mechanisms of sudden unexpected death in epilepsy is autonomic, i.e., cardiac abnormalities during and between seizures.9,11 Thus, although progress continues to be made in the field of sudden unexpected death in epilepsy in the last decade, the dearth of published data about the relationship between Down syndrome and sudden unexpected death in epilepsy encouraged us to address some questions regarding this specific topic. As described previously, seizures in Down syndrome could be considered an epiphenomenon, i.e., they could be a consequence of the neurological alterations, both morphological and physiological, normally observed in this population.12,13 Interestingly, the prevalence of epilepsy in individuals with Down syndrome increases with age, reaching almost 50% of all Down syndrome patients over 50 years of age.12 In general terms, approximately 8% of individuals with Down syndrome have seizure disorders that have been classified as partial seizures (47%), infantile spasms (32%) or generalized tonic-clonic seizures (21%).12 Another interesting characteristic is the bimodal distribution of seizure onset: 40% of Down syndrome patients begin having seizures before the age of 1 year, and 40% experience seizures for the first time in the third decade of life.12 The occurrence of primarily infantile spasms predominates in the younger group, while partial seizures are more frequently observed in the older Down syndrome group. Tonic-clonic seizures seem to be equally distributed throughout life12,14. Taken together, these data raise the following question: Is there a risk of sudden unexpected death in epilepsy in individuals with Down syndrome who do not respond optimally to the treatment established by neurologists to control their seizures? Unfortunately, the answer is yes. As previously mentioned, a number of associated factors for sudden unexpected death in epilepsy have been reported, but the results are not wholly consistent between studies. The factors examined include refractoriness of the epileptic condition, presence of generalized tonic-clonic seizures, early onset of epilepsy, antiepileptic medication (polytherapy with antiepileptic drugs), young age, and duration of the seizure disorder.9,10 In addition, although the different mechanisms may play separate roles in different cases, putative pathomechanisms include cardiac arrhythmia due to myocardial ischemia, electrolyte disturbances, arrhythmogenic drugs or transmission of epileptic activity via the autonomic nervous system to the heart.11 In evaluating the data of these conditions concurrently with data from Down syndrome patients with seizure disorders, we can assume that these individuals may be considered potential candidates for sudden unexpected death in epilepsy. Moreover, we cannot fail to mention that approximately 40% of individuals with Down syndrome have congenital cardiac anomalies,15,16 doubling the chance of having a fatal event and redoubling our concern for these individuals. On the basis of this probability, how might we proceed We are unable to prevent the occurrence of these illnesses or completely reverse the clinical picture when both have already occurred. However, a few simple, common, established strategies can be concurrently implemented by neuroscientists. First, it should be asked whether the search for some seizure-related event should be part of the clinical, routine checks in Down syndrome patients. Second, if this search is made, and considering that many individuals with Down syndrome have congenital heart defects, it should be asked whether palliative care of the cardiovascular system of these patients should be redoubled. To accomplish this redoubling, indispensable strategies, such as taking a detailed cardiovascular history and screening for symptoms of cardiovascular disease, cardiovascular risk factors and prior cardiac findings (electrocardiogram and echocardiogram), should be conducted frequently. Third, physicians who follow these patients should work collaboratively and should suggest that these patients be treated in a translational manner, i.e., that treatments should integrate advancements in basic science with clinical trials, taking research from “bench-to-bedside.” 17 To do this effectively, some important well-established translational strategies18 should be adopted, such as maintaining a healthy weight, consuming a healthy and balanced diet, avoiding smoking, limiting alcohol consumption, maintaining regular physical activity (under the supervision of a qualified professional), maintaining good quality sleep and improving stress management by making time for relaxation and learning healthier coping strategies. Additionally, establishing a diet with omega-3 fatty acids from fish or fish oil supplements is strongly recommended. On the whole, we strongly believe it is time to establish a taskforce to assess the state of knowledge regarding the occurrence of sudden unexpected death in epilepsy in Down syndrome, including clinical management, research directions, and educational, social and cultural efforts. To provide a better future for these patients, a list of the current problems should be compiled and analyzed to determine which feasibly-solved problems merit the most attention. Finally, neuroscientists must be faithful to concepts originating in eastern cultures: Great achievements are possible when you give importance to small beginnings.​. Figure 1 The hypothesis that cardiovascular disturbances and hence sudden unexpected death in epilepsy, at least in some cases, could be related to the occurrence of refractory epilepsy in people with Down syndrome is proposed. Furthermore, ...

A brief review intended as information to the readership of Clinics on papers recently published under various medical headings in Brazilian scientific journals recently indexed or about to be indexed in ISI-THOMSON Journal Citation Reports. Journals covered in this review are Acta Ortopédica Brasileira, Arquivos Brasileiros de Cardiologia, Jornal Brasileiro de Pneumologia, Revista Brasileira de Cirurgia Cardiovascular and Revista da Associação Médica Brasileira.

Dear Editor, We have read with great interest the recently published article titled, “The relationship between hyperuricemia and the risk of contrast-induced nephropathy after percutaneous coronary intervention in patients with relatively normal serum creatinine”, by Yong Liu et al. (1). In that well-presented paper, the authors investigated the value of hyperuricemia in predicting the risk of contrast-induced nephropathy (CIN) in patients with relatively normal serum creatinine who are undergoing CIN. They demonstrated that CIN might develop in patients with normal creatinine levels. Hyperuricemia is a significant and independent predictor of CIN after percutaneous coronary intervention (PCI) and results in significantly increased in-hospital mortality and CIN incidence, which requires renal replacement therapy after PCI. Thus, despite having normal baseline creatinine levels, patients with hyperuricemia, an intra-aortic balloon pump, emergent PCI, or older age should receive more comprehensive renal prophylaxis to reduce the occurrence of CIN. CIN has been recognized as a serious complication of PCI and may cause increased morbidity and mortality. CIN is one of the most important reasons for hospital-acquired renal failure and can cause prolonged hospitalization, increased cost and incidence of renal and cardiovascular events, and mortality. Elderly patients have a higher risk of CIN because of decreased renal reserve. In addition, some factors, such as an estimated glomerular filtration rate (eGFR) of 200 mL have been identified as risk factors for CIN after PCI (2). Additionally, alcohol consumption and the arterial blood pressure level before contrast exposure may be associated with CIN. Hypertriglyceridemia, metabolic syndrome, an impaired fasting glucose level, and multivessel disease may also be associated with a higher incidence of CIN (3). Some medications, including renin-angiotensin-aldosterone system medications, may also be related to CIN (4). It would have been interesting for the authors to provide information about these factors in this study. Finally, the authors used the Cockcroft-Gault equation to measure eGFR. The Cockcroft-Gault equation may underestimate eGFR in younger age groups and may overestimate eGFR in older individuals compared with the Modification of Diet in Renal Disease (MDRD) formula (5). Although the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently published an equation for eGFR using the same variables (serum creatinine level, age, sex, and race) as the MDRD formula, the CKD-EPI equation more accurately categorized individuals with respect to long-term clinical risk (6). In addition, even mild chronic kidney dysfunction, defined as an eGFR

Recent original scientific contributions published in selected Brazilian periodicals and classifiable under cardiovascular and pulmonary subject categories cover a wide range of sub specialties, both clinical and experimental. Because they appear in journals with only recently enhanced visibility, we have decided to highlight a number of specific items appeared in four Brazilian journals, because we understand that this is an important subsidy to keep our readership adequately informed. These papers cover extensive sub-areas in both fields.