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OBJECTIVES: To identify the most cited articles in general surgery published by Brazilian authors. INTRODUCTION: There are several ways for the international community to recognize the quality of a scientific article. Although controversial, the most widely used and reliable methodology to identify the importance of an article is citation analysis. METHODS: A search using the Institute for Scientific Information citation database (Science Citation Index Expanded) was performed to identify highly cited Brazilian papers published in twenty-six highly cited general surgery journals, selected based on their elevated impact factors, from 1970 to 2009. Further analysis was done on the 65 most-cited papers. RESULTS: We identified 1,713 Brazilian articles, from which nine papers emerged as classics (more than 100 citations received). For the Brazilian contributions, a total increase of about 21-fold was evident between 1970 and 2009. Although several topics were covered, articles covering trauma, oncology and organ transplantation were the most cited. The majority of classic studies were done with international cooperation. CONCLUSIONS: This study identified the most influential Brazilian articles published in internationally renowned general surgery journals.

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).

CLINICS covers all medical areas. This editorial highlights the field of pulmonary research. We have selected papers published from 2010-11 concerning the Continuously Variable Rating concept, which we have recently put forward as an alternative and hopefully superior method of evaluating published scientific papers (1).

OBJECTIVE: This study aimed to develop a new histological scoring system for use in a partial-thickness cartilage repair animal model. Although previous papers have investigated the regeneration of articular cartilage, the good results achieved in small animals have not been replicated in large animal models or humans, possibly because of the frequent use of models with perforation of the subchondral bone plates. Partial-thickness lesions spare the subchondral bone, and this pattern is the most frequent in humans; therefore, new therapies should be tested using this model. However, no specific histological score exists to evaluate partial-thickness model results. METHODS: Histological sections from 30 ovine knees were reviewed to develop a new scoring system. The sections were subjected to H&E, Safranin O, and Masson’s trichrome staining. RESULTS: This paper describes a new scoring tool that is divided into sections in detail: repair of tissue inside the lesion, cartilage around the lesion and degenerative changes at the base of the lesion. Scores range from 0 to 21; a higher score indicates better cartilage repair. DISCUSSION: Unlike existing tools, this new scale does not assign points for the positioning of a tidemark; we propose evaluation of the degenerative changes to the subchondral bone and calcified cartilage layer. It is necessary to remove the whole joint to access and study the evolution of the lesion as well as the surrounding tissue. CONCLUSION: This article emphasizes the importance of a partial-thickness animal model of cartilage repair and presents a new histological scoring system.

OBJECTIVE: To make recent selected publications on the locomotor system available to the readership of Clinics. METHOD: A general survey of articles published in selected Brazilian journals was inspected and 91 articles were critically analyzed. They were categorized and briefly described. A final summary of themes is reproduced here. RESULTS: Papers fall into two main categories: articular and muscular pathology and therapeutics; medical sports. A number of papers are not classifiable under these headings. CONCLUSION: The locomotor system has been extensively analyzed and discussed in the Brazilian scientific press in recent years. Not surprisingly, knee and ankle pathology, soccer and running are dominant themes.

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

In this September 2009 issue of Clinics we highlight a study by Meneghini et al. on the effect of Memantine, a N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer’s disease on cardiomyocites. They found that the reduction of nuclear size of rats exposed to a cold stress is effectively prevented by simultaneous treatment with memantine. We publish nine papers on Clinical Science and three other reports on non clinical research. Bueno et al. evaluated the reasons for resubmitting research projects to the Research Ethics Committee of a University Hospital in Sao Paulo Brazil, and found that the main reasons for returning the projects to the researchers were the use of inadequate language and/or difficulty understanding the informed consent form, lack of information about the protocol in the informed consent form, as well as doubts regarding methodological and statistical issues of the protocol. Otherreasons involved lack of accuracy or incomplete documentation, need of clarification, approval for participation of external entities, and lack of information on financial support. Bittencourt et al. evaluated HFE and non-HFE gene mutations in Brazilian patients with hereditary hemochromatosis and found that one-third of Brazilian subjects with the classical phenotype of HH do not carry HFE or other mutations that are currently associated with the disease in Caucasians. This observation suggests a role for other yet unknown mutations in the aforementioned genes or in other genes involved in iron homeostasis in the pathogenesis of hereditary hemochromatosis in Brazil. Kamulegeya et al. investigated the epidemiological characteristics of maxillofacial fractures and associated fractures in 132 patients seen in the Oral Surgery Unit of Mulago Hospital, Kampala, Uganda through a six-month prospective study, which included socio-demographic factors, type and etiology of injury, additional fractures, and post-surgery complications and recommend that anticipated changes in maxillofacial trauma trends necessitate regular epidemiologic studies of facial fractures to allow for development and implementation of timely novel preventive measures. Brandao et al. followed 53 patients with medullar thyroid carcinoma, a neoplasia of intermediate prognosis and differentiation, which does not always respond predictably to known treatments. They found that clinical and pathological aspects of surgically treated patients are predictors of disease progression. Specifically, even treated cervical lymph node metastases are significantly correlated with disease progression. Carvalho et al. evaluated crack cocaine use practices, risk behaviors associated with HIV infection among drug users, and their involvement with violence in 350 drug users attending drug abuse treatment clinics in Sao Paulo, Brazil. A high HIV prevalence and associated risky sexual behaviors were observed among crack cocaine users. The society and the authorities that deal with violence related to crack users and drug trafficking should be aware of these problems. Campos et al. endeavored to identify factors associated with increased levels of self-reported quality of life among HIV-infected patients after four months of antiretroviral therapy. Patients were recruited at two public health referral centers for AIDS in the city of Belo Horizonte, Brazil, for a prospective adherence study. Authors highlight the importance of modifiable factors such as psychiatric symptoms and treatment-related variables that may contribute to a better quality of life among patients initiating treatment. Considering that poor quality of life is related to non-adherence to antiretroviral therapy, careful clinical monitoring of these factors may contribute to ensuring the long-term effectiveness of antiretroviral regimens. Meyer et al. evaluated, by means of the Inflammatory Bowel Disease Questionnaire the quality of life of 36 ulcerative colitis patients submitted to proctocolectomy with sphincter preservation using J-pouch reconstruction over ten years ago. They concluded that the possibility of sphincter preservation should always be taken into account, since patients remain clinically stable and have a high quality of life even after long periods. Miot et al. estimated oculometric parameters of 15 cases of Graves’ ophthalmopathy in comparison to 12 healthy eyes using digital photography and digital image analysis. This comparative analysis suggests that eye proptosis is related to an asymmetric increase in lateral oculometric measures, and that standardized digital photographs can be used in clinical practice to objectively estimate oculometric parameters of Graves’ ophthalmopathy patients. Vaz et al. sought to identify the participation of the coagulation system in the differential diagnosis of pleural effusions through the laboratory profile of coagulation and fibrinolysis in 54 pleural fluids (15 transudates and 39 exudates). The coagulation system was found to play an important role in the development of pleural diseases. Coagulation tests show differences between transudates and exudates but not among exudate subgroups. Understanding the pathophysiological mechanisms of pleural disorders may help to define new diagnostic and therapeutic approaches. Pai et al. studied 98 pelvic halves of embalmed cadavers, in which the origin and course of the obturator artery were traced and noted. The data obtained in this study show that it is more common to find an abnormal obturator artery than was reported previously, and this observation has implications for pelvic surgeons and is of academic interest to anatomists. Surgeons dealing with direct, indirect, femoral, or obturator hernias need to be aware of these variations and their close proximity to the femoral ring. Cardoso et al. identified the scientific production of tenured faculty from the Universidade de Sao Paulo, Faculdade de Medicina performed from 2001 to 2006, and that it is possible to analyze this by the number of papers published by full professors, taking into account not only their academic position and influence, but also the fact that publication is an opportunity to stimulate joint projects with other members of the same institution. Zanoni et al. investigated mesenteric microcirculatory dysfunctions, bacterial translocation phenomenon, and hemodynamic/metabolic disturbances in a rat model of intestinal obstruction and ischemia. They found that Intestinal obstruction and ischemia in rats is a relevant model for the in vivo study of mesenteric microcirculatory dysfunction and the occurrence of bacterial translocation. This model parallels the events implicated in multiple organ dysfunction (MOD) and death. We also publish 3 case reports

This issue of Clinics closes our fourth year of existence and the first in which our impact factor will be formally calculated by the Journal of Citation Reports of ISI Web of Knowledge. During this year we have experienced a 40% increase in the total of submitted papers, with a 400% increase in submissions from outside Brazil, to an all time high approximating 60 out of 400 papers. We have also increased the total number of published papers from 91 (in 2007) to 111, 10 of which were review articles. We shall be starting the year of 2009 by becoming a monthly journal. In this issue we publish 18 original research articles and two review articles. We highlight an article by Costa et al, who evaluated the effects of obesity on the pulmonary function, comparing inspiratory and expiratory reserve volumes, as well as maximal voluntary ventilation of 20 obese (BMI > 35 kg/m2) vs. 20 non-obese women. All were sedentary non-smokers aged 20–35. Results clearly show that although obese women have greater inspiratory reserve, they have smaller expiratory reserve and lower maximal voluntary respiration. This indicates damage to the chest mechanics caused by obesity. Carvalho et al. investigated the relationship between heart rate reserve and oxygen uptake reserve in heart failure patients on optimized and non-optimized beta-blocker therapy. They find that the relationship between the percentage of oxygen consumption reserve and percentage of heart rate reserve is reliable in patients on optimized beta-blocker therapy, but unreliable in non-optimized heart failure patients. Colombo et al. report the outcomes of laparoscopic partial cystectomy performed in 6 cases at 3 institutions; 3 cases of urachal adenocarcinoma and 3 cases of bladder transitional cell carcinoma and conclude that in selected cases this procedure is feasible and safe, offering a promising and minimally invasive therapeutic alternative. Conforto et al. investigated changes in excitability of the unaffected hemisphere in chronic stroke patients after somatosensory stimulation of the paretic hand. They find that somatosensory stimulation did not influence excitability as measured by motor threshold, short-interval intracortical inhibition or intracortical facilitation. Thy also find that better motor function was correlated with deeper short-interval intracortical inhibition. Vieira analyzed a Portuguese translation of the postgraduate hospital educational environment measure (PHEEM) questionnaire as a measure of quality of instruction and as a key factor predicting academic achievement, by administering it to 306 medical residents. The conclusion is that the teaching section, or quality of instruction is the best indicator of academic achievement. Moure et al. reviewed the histopathologic diagnoses of 38 cases of primary cicatricial alopecias, sub-typed them into different primary cicatricial alopecias: chronic cutaneous lupus (17), lichen planus pilaris (4), pseudopelade of Brocq (12), folliculitis decalvans (3), dissecting folliculitis (1), and non-specific scarring alopecia (1). They conclude that this approach using systematic criteria allowed for a more accurate diagnosis. Ciolac et al. applied acute aerobic exercises to 50 hypertensive patients monitored for 24h with respect to ambulatory (A) blood pressure after an aerobic exercise session (post-exercise) and a control period (control), in random order. They find that a single bout of aerobic exercise reduced 24h ambulatory blood pressure levels in long-term-treated hypertensive patients and increased the percentage of patients reaching normal ambulatory blood pressure values. They suggest that aerobic exercise may have a potential role in blood pressure management of long-term-treated hypertensive. Kato et al. estimated pretreatment prostate tumor volume based on total serum PSA and define a simple method that allows for estimation of tumor volume before treatment, which can help to establish a better therapeutic strategy for each patient. Cunha et al. experimentally compared conventional static stretching and muscle chain stretching, as proposed by the global posture reeducation method in patients with chronic neck pain. Conventional stretching and muscle chain stretching were equally effective in reducing pain and improving the range of motion and quality of life of 33 female patients with chronic neck pain, both immediately after treatment and after a six-week follow-up period. Munia et al. compared the results of two levels of video-assisted thoracoscopic sympathectomy (T3–T4 vs. T4) for treating axillary sudoresis at the initial and at six and twelve month follow-ups. They conclude that both techniques were effective for treating axillary hyperhidrosis, but that the T4 group showed milder compensatory hyperhidrosis and greater patient satisfaction at the one-year follow-up. Valadares et al. analyzed the prevalence of sexual dysfunction and its associated factors in 315 Brazilian-born women aged 40–65 years, with 11 years or more of formal education, through a cross sectional population based study. They find that sexual dysfunction was positively associated with aging and hot flashes. They also find that having a sexual partner and feeling well were factors associated with lower sexual dysfunction scores. Martinelli et al. evaluate the quality of life and its association with cardiovascular risk factors in a Community Health Care Program population in a study which included 332 individuals that had attended a specific community event on health care education. They conclude that quality of life was decreased in the presence of cardiovascular risk factors, such as diabetes mellitus, dyslipidemia, and obesity. Conversely, male gender and regular physical activity had protective effects on quality of life. Andrade-Alegre et al. review open thoracotomy and decortication for chronic empyema as performed in 85 patients and note that these patients were operated with no mortality, 9% morbidity, no recurrence of empyema and excellent functional results. They suggest that the validation of other surgical approaches should be based on comparative, prospective, and controlled studies. Branco et al. compare hand-assisted and pure laparoscopic techniques in live donor nephrectomy and observed that the latter technique has some advantages in terms of the warm ischemia time, time to first oral intake, length of hospital stay, and post-operative donor complications. Galia et al. evaluated the biocompatibility of lyophilized bovine bone manufactured according to a novel preparation process. The following assessments were performed in vitro cytotoxicity, in vivo acute systemic toxicity, in vivo oral irritation potential, in vitro pyrogenic reaction, and bioburden, yelding an end-product with excellent biocompatibility. They conclude that the protocol changes established by them to prepare lyophilized bovine cancellous bone at a semi-industrial scale is reproducible and yielded a product with excellent biocompatibility. Habib et al. evaluated the effect of ginger extract on the expression of NFκB and TNF-α in liver cancer-induced male Wistar rats and conclude that it significantly reduced the elevated expression of NFκB and TNF-α in rats with liver cancer. They suggest that ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFκB through the suppression of the pro-inflammatory TNF-α. Potu et al. examined the efficacy of maternally administered petroleum ether extract of the Cissus quadrangularis plant on the development of long bones during the intra-uterine development in rats using alizarin red S, alcian blue staining and morphometric analysis by Scion image software, and showed an osteostimulant role of the above plant. Madhyastha et al. compared vitamin A and leucovorin for the prevention of methotrexate-induced micronuclei production in rat bone marrow through micro nuclei assay of rat bone marrow erythrocytes because it is a predictive assay for chromosomal aberrations, genetic diseases, and carcinogenesis. They conclude that both vitamin A and leucovorin provided significant protection against genetic damage induced by methotrexate and that leucovorin did not differ from vitamin A in its ability to prevent methotrexate-induced micronuclei formation. Reis and Laranjeira provide an interesting narrative review of the concepts, history, functions, methods, development, and theoretical bases for the use of halfway houses for alcohol dependents, from theoretical bases to the implications for the organization of facilities. Azoubel et al. provide a review of 30 clinical studies on the use of hyperosmotic-hyperoncotic solutions during surgeries. Reduced positive fluid balance, increased cardiac index, and decreased systemic vascular resistance were the main beneficial effects of using hypertonic solutions. We also publish three case reports.

Since the outbreak of severe acute respiratory coronavirus 2 (SARS-CoV-2), the coronavirus disease 2019 has had a wide range of effects on human health. This paper summarizes the data related to the effects of the SARS-CoV-2 infection on human reproduction. Both the male and female reproductive tract express high levels of receptors and proteins needed for viral cell entry. There is presently no evidence that gametes are affected by the infection. Male fertility may be temporarily reduced due to inflammatory responses following infection. The endometrium is highly susceptible to SARS-CoV-2 cell entry; however, it remains unclear whether this could alter receptivity and embryo implantation. Menstrual cycle changes were reported in women who experienced severe infection; however, they tended to be reversible. For couples undergoing assisted reproduction treatment, the pandemic led to a significant psychological burden, with changes in lifestyle that could directly affect the success of the treatment. Human reproduction societies recommend screening all patients prior to cycle initiation and avoiding treatment of women with severe comorbidities until the pandemic is under control. Finally, for pregnant women, it is expected that the infection is more severe in women in the third trimester and in those with comorbidities. Those who are symptomatic for SARS-CoV-2 are more likely to have increased rates of prematurity and intrapartum fetal distress than those who are asymptomatic. Vertical transmission cannot be completely ruled out, but neonatal infection rates are low. Vaccination appears to be safe and is indicated for use in pregnant and lactating women because the benefits outweigh the risks.

OBJECTIVES: Dengue cases range from asymptomatic to severe, eventually leading to hospitalization and death. Timely and appropriate management is critical to reduce morbidity. Since 1980, dengue has spread throughout Brazil, affecting an increasing number of individuals. This paper describes age and regional differences in dengue’s clinical presentation and associated risk of hospitalization based on more than 5 million cases reported to the Brazilian Ministry of Health from 2000-2014. METHODS: We performed a retrospective analysis of ∼5,450,000 dengue cases, relating clinical manifestations and the risk of hospitalization to age, gender, previous infection by dengue, dengue virus serotype, years of formal education, delay to first attendance and the occurrence of dengue during outbreaks and in different Brazilian regions. RESULTS: Complicated forms of dengue occurred more frequently among those younger than 10 years (3.12% vs 1.92%) and those with dengue virus 2 infection (7.65% vs 2.42%), with a delay to first attendance >;2 days (3.18% vs 0.82%) and with ≤4 years of formal education (2.02% vs 1.46%). The risk of hospitalization was higher among those aged 6-10 years old (OR 4.57; 95% CI 1.43-29.96) and those who were infected by dengue virus 2 (OR 6.36; 95% CI 2.52-16.06), who lived in the Northeast region (OR 1.38; 95% CI 1.11-2.10) and who delayed first attendance by >;5 days (composite OR 3.15; 95% CI 1.33-8.9). CONCLUSIONS: In Brazil, the occurrence of severe dengue and related hospitalization is associated with being younger than 10 years old, being infected by dengue virus 2 or 3, living in the Northeast region (the poorest and the second most populated) and delaying first attendance for more than 2 days.

We read the paper by Oliveira C et al. () describing the hemodynamic effects of different maternal positions on maternal and fetal cardiovascular and respiratory indices with interest. The authors observed no differences in the measured parameters (maternal heart rate, blood pressure, oxygen saturation, respiratory rate or fetal heart rate) between the left lateral position, Fowler’s position and supine position, but they did observe reductions in the maternal respiratory rate and systolic blood pressure in Fowler’s position compared with lying [...]

Cotas do Programa de Pos-Graduacao do Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) Fundacao de Amparo a Pesquisa de Sao Paulo (FAPESP) This study reviewed the effectiveness of school-based physical activity interventions aimed at reducing overweight, obesity and hypertension in children. We searched 14 databases and analyzed studies published between April 2009 and September 2012. Only randomized controlled trials performed at the school level that included elements of physical activity but did not include nutritional co-interventions were analyzed. Studies were assessed by two recommended tools (EPHPP and GRADE), and the standardized mean differences with 95% confidence intervals were collected for a random-effect meta-analysis. A total of 12 papers were included in the meta-analysis, and these were divided according to three outcomes: body mass index (11 trials, n = 4,273, −0.02, 95% CI: −0.13 to 0.17, p = 0.8); body weight (5 trials, n = 1,330, −0.07, 95% CI: −0.18 to 0.04, p = 0.2); and blood pressure (6 trials, n = 1,549), including systolic (0.11, 95% CI: −0.10 to 0.31, p = 0.3) and diastolic pressure (−0.00, 95% CI: −0.10 to 0.10, p = 0.9). This meta-analysis of data from 11 randomized, school-based physical activity interventions suggests that, regardless of the potential benefits of physical activity in the school environment, the interventions did not have a statistically significant effect. However, it is difficult to generalize from these results because the duration, intensity and type of physical activity used in the interventions varied greatly. Universidade de São Paulo Hospital das Clinicas Faculdade de Medicina Federal University of São Paulo Federal University of São Paulo Pediatrics Department, Nutrology UNIFESP, Pediatrics Department, Nutrology 09/12438-5 SciELO

Although the diagnosis of Graves' orbitopathy is primarily made clinically based on laboratory tests indicative of thyroid dysfunction and autoimmunity, imaging studies, such as computed tomography, magnetic resonance imaging, ultrasound and color Doppler imaging, play an important role both in the diagnosis and follow-up after clinical or surgical treatment of the disease. Imaging studies can be used to evaluate morphological abnormalities of the orbital structures during the diagnostic workup when a differential diagnosis versus other orbital diseases is needed. Imaging may also be useful to distinguish the inflammatory early stage from the inactive stage of the disease. Finally, imaging studies can be of great help in identifying patients prone to develop dysthyroid optic neuropathy and therefore enabling the timely diagnosis and treatment of the condition, avoiding permanent visual loss. In this paper, we review the imaging modalities that aid in the diagnosis and management of Graves' orbitopathy, with special emphasis on the diagnosis of optic nerve dysfunction in this condition.

As a multidisciplinary medical journal CLINICS has covered virtually every medical area. We here highlight one of our strongest fields, Pediatrics, responsible for slightly over 10% of all our original research papers over 2010-11.

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 exprimental. 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.

The number of pediatric kidney transplants has been increasing in many centers worldwide, as the procedure provides long-lasting and favorable outcomes; however, few papers have addressed the immediate postoperative care of this unique population. Herein, we describe the management of these patients in the early postoperative phase. After the surgical procedure, children should ideally be managed in a pediatric intensive care unit, and special attention should be given to fluid balance, electrolyte disturbances and blood pressure control. Antibiotic and antiviral prophylaxes are usually performed and are based on the recipient and donor characteristics. Thrombotic prophylaxis is recommended for children at high risk for thrombosis, although consensus on the optimum therapy is lacking. Image exams are essential for good graft control, and Doppler ultrasound must be routinely performed on the first operative day and promptly repeated if there is any suspicion of kidney dysfunction. Abdominal drains can be helpful for surveillance in patients with increased risk of surgical complications, such as urinary fistula or bleeding, but are not routinely required. The immunosuppressive regimen starts before or at the time of kidney transplantation and is usually based on induction with monoclonal or polyclonal antibodies, depending on the immunological risk, and maintenance with a calcineurin inhibitor (tacrolimus or ciclosporin), an anti-proliferative agent (mycophenolate or azathioprine) and steroids.

Since studies show that an unfavorable environment during intrauterine development predisposes individuals to several diseases in adulthood, our objective is to assess the relation between fetal growth restriction and chronic renal disease in adults. We searched four different electronic databases through November 2017: CENTRAL, EMBASE, LILACS and MEDLINE. We selected studies with longitudinal or transversal designs associating kidney function in adulthood with low birth weight. Two reviewers evaluated the inclusion criteria and the risk of bias and extracted data from the included papers. Thirteen studies were selected for the systematic review and meta-analysis. We observed increased risks of presenting end-stage renal disease (risk ratio 1.31, 95% confidence interval: 1.17, 1.47), a lower glomerular filtration rate (ml/min) (mean difference 7.14; 95% confidence interval: -12.12, -2.16), microalbuminuria (risk ratio 1.40; 95% confidence interval: 1.28, 1.52) and a small increase in the albumin/creatinine ratio (mean difference 0.46; 95% confidence interval: 0.03, 0.90) in the low birth weight patients, compared with control group. These findings suggest that low birth weight is associated with renal dysfunction in adults.

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.

Odontogenic myxoma is a slow-growing, painless, and site-aggressive tumor.1 Large-sized lesions may cause tooth dislodgement and cortical bone expansion.2,3 Since pain and hypoesthesia are not common, the lesion may reach a considerable size before the patient perceives its existence and seeks treatment.4 This lesion is not encapsulated, thus promoting significant infiltration into the adjacent medullar bone. In addition, this condition carries a high recurrence rate. The treatment of choice for this condition is surgical excision by either enucleation, curettage, or block resection.5 The average recurrence rate is 25%, especially when more conservative treatments are used.1,6 Cryotherapy has been used in the maxillofacial region for the removal of neoplasias or abnormal cell elements with no need for extensive segmental resection.7–9 Liquid nitrogen is the most efficient type of freezing spray available for bone cryosurgery.10 The most commonly observed complications associated with cryotherapy are pathologic fractures7,10,11 and bone sequestra.7,10 This paper reports the case of a recurrent mandibular myxoma diagnosed 30 years after the initial lesion treatment, and discusses the possibility of conservative management of extensive odontogenic lesions with high recurrence rates.

The purpose of this paper is to supply a narrative review of the concepts, history, functions, methods, development and theoretical bases for the use of halfway houses for patients with mental disorders, and their correlations, for the net construction of chemical dependence model. This theme, in spite of its relevance, is still infrequently explored in the national literature. The authors report international and national uses of this model and discuss its applicability for the continuity of services for alcohol dependents. The results suggest that this area is in need of more attention and interest for future research.

Despite the high prevalence of depression and hypertension, the relationship between the two diseases has received little attention. This paper reviews the epidemiological, pathophysiological, and prognostic aspects of this association, as well as its implications for treatment. A Medline search was conducted using the following key words: depression, blood pressure, blood pressure variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive agents, and genetics, from 1980 to 2004. We found descriptions of increased prevalence of hypertension in depressed patients, increased prevalence of depression in hypertensive patients, association between depressive symptomatology and hypotension, and alteration of the circadian variation of blood pressure in depressed patients. There is considerable evidence suggesting that hyperreactivity of the sympathetic nervous system and genetic influences are the underlying mechanisms in the relationship between depression and hypertension. Depression can negatively affect the course of hypertensive illness. Additionally, the use of antidepressive agents can interfere with blood pressure control of patients with hypertension by inducing changes in blood pressure and orthostatic hypotension. Apesar das altas prevalências de hipertensão arterial sistêmica e de depressão, o estudo da relação entre depressão e pressão arterial tem recebido pouca atenção da literatura. Nesse artigo são revisados os aspectos epidemiológicos, patofisiológicos, prognósticos e implicações no tratamento, relacionados à associação entre depressão e hipertensão arterial sistêmica. O método utilizado foi consulta ao banco de dados bibliográficos Medline, utilizando-se as palavras chave depression, blood pressure, blood pressure variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive agents e genetics, no período de 1980 a 2004. Encontramos descrições de prevalência aumentada de hipertensão em pacientes deprimidos, prevalência aumentada de depressão em pacientes hipertensos, associação entre sintomatologia depressiva e hipotensão e alteração da variação circadiana da pressão arterial de pacientes deprimidos. Acredita-se que mecanismos envolvendo hiperatividade de sistema nervoso simpático e influências genéticas possam ser a base fisiopatológica da relação entre depressão e hipertensão arterial sistêmica. Além disso, a presença de depressão pode piorar o curso da doença hipertensiva, e o uso medicações antidepressivas pode induzir aumento de pressão arterial, diminuição de pressão arterial e hipotensão ortostática, dificultando o manejo de pacientes com hipertensão arterial sistêmica.

PURPOSE: The aim of this paper is to report our experience in the creation of arteriovenous fistulas in children by using microsurgical vascular techniques, with emphasis on the details of the surgical technique. METHODS: The children underwent surgery from July 1997 to March 2004. Operating loupes (magnification: 3.5X) were used by the entire surgical team. After dissection and adequate mobilization, the vein was anastomosed to the artery in an end-to-lateral fashion by using 4 separate 7/0 or 8/0 prolene running sutures. RESULTS: Twenty nine children underwent 33 fistula creations - 21 radiocephalic, 6 brachiocephalic, 4 brachiobasilic, and 2 saphenofemoral. Primary patency was achieved in 17/21 (80.9%) of the radiocephalic fistulas, 5/6(83.3%) of the brachiocephalic, 3/4 (75.0%) of the brachiobasilic, and 2/2 (100%) of saphenofemoral. Two patients developed fistula occlusion and radial artery thrombosis, and in 2 others, radiocephalic fistulas became occluded in the first or second postoperative week. In the late postoperative period, the saphenofemoral fistulas were responsible for significant edema formation in the lower extremity; an aneurysm formed in a brachiocephalic fistula after a long period of utilization. As to the patency of the different sites of fistulas, the brachiocephalic and brachiobasilic fistulas had the same incidence of patency as the radiocephalic fistulas (P >;.05). CONCLUSIONS: This experience indicates that the arteriovenous fistulas are a satisfactory method for providing hemodialysis in children. The utilization of microsurgical techniques and some technical refinements herein described permit the attainment of high patency rates of the fistulas. OBJETIVO: Relatar a experiência dos autores na execução de fístulas artério-venosas em crianças, com a utilização dos recursos da microcirurgia vascular, com especial ênfase aos detalhes de técnica cirúrgica. MÉTODOS: Os pacientes foram operados entre julho de 1997 e março de 2004. Foram utilizadas lupas cirúrgicas (aumento de 3,5 vezes). Após a dissecção da veia e da artéria, a anastomose veno-arterial foi realizada de forma término-lateral, com quatro suturas contínuas de fio 7/0 ou 8/0. RESULTADOS: Vinte e nove crianças foram operadas para a realização de 33 fístulas - 21 rádio-cefálicas, 6 bráquio-cefálicas, 4 bráquio-basílicas e 2 safeno-femorais. Obteve-se permeabilidade em 17/21 (80,9%) fístulas rádio-cefálicas, 5/6 (83,3%) bráquio-cefálicas, 3/4 (75,0%) bráquio-basílicas e 2/2 (100%) safeno-femorais. 2 pacientes apresentaram obstrução da fístula e da artéria radial e 2 outras fístulas rádio-cefálicas obstruíram-se entre a primeira e segunda semana de pós-operatório. Tardiamente, verificou-se que as fístulas safeno-femorais causaram edema do membro inferior correspondente e houve formação de aneurisma em uma fístula bráquio-cefálica. Quanto à permeabilidade, verificou-se que as fístulas bráquio-cefálicas e bráquio-basílicas apresentaram a mesma incidência de permeabilidade em comparação com as fístulas rádio-cefálicas (p>;0,05). CONCLUSÃO: A presente casuística demonstra que as fístulas artério-venosas persistem como um bom acesso vascular para hemodiálise em crianças. A utilização de microcirurgia e alguns detalhes técnicos aqui descritos permitem a obtenção de bons índices de permeabilidade das fístulas.

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.

Twenty-five years have passed since the first lung transplant was performed at the Instituto do Coracao (INCOR) do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo. On October 16th, 1990, a 26-year-old woman with severe pulmonary fibrosis and secondary pulmonary hypertension underwent a single left lung transplant but only survived for 12 days, dying due to sepsis and diffuse alveolar damage. This occurred several months after the first and second 1 lung transplants in Brazil and seven years after the first in the world, which had been performed by Dr. Cooper in Toronto 2. Over a five-year period, nine more cases were performed, with the longest post-operative survival being 4 years. Despite the dedication of all the personnel involved with the program at that time, seven patients were never discharged due to acute respiratory failure and infection. At present, primary graft dysfunction remains a complication of transplant procedures, but in 1995, it seemed an almost insurmountable barrier. Despite the strong desire to continue performing this procedure, the group was not adequately prepared to continue in this field and the program was discontinued. In parallel, pulmonologists and surgeons sought training at other lung transplant centers and research in the field was initiated at our laboratory in the Medical School. Because bronchial healing remained a problem in clinical cases, it was chosen as a starting point for research. Using animal models of bronchial anastomosis and lung transplant as well as an established methodology for the evaluation of airway mucous clearance, the effect of immunosuppressive drugs was tested. Cyclosporin 3,5, Prednisone 6,7, Micophenolate 8 and combined therapies, including Tacrolimus 9,10, were tested and all drugs had a negative impact on mucous clearance. On August 9th 2000, a single right lung transplant was performed on a 32-year-old male with silicosis. The post-operative period was uneventful and the patient is still alive fifteen years later. The main problems concerning intraoperative care, post-operative care and immunosuppression seemed to be solved. However, in the following three years we performed ten more procedures, of which only two patients survived for more than one year. Although only two patients of this period are still alive, the low survival rate indicated that there was still something lacking. At that time, the current knowledge and infrastructure were considered sufficient, but it was clear that unless a dedicated team was established, we could not proceed in this field. In 2003, a multi-professional and multi-disciplinary team was formed that included pulmonologists, surgeons, infectologists, nurses, physiotherapists, nutritionists, social workers and psychologists. We established a routine of morning rounds in ICU and on the wards; assessment meetings; scientific meetings and journal clubs. Based on candidate selection criteria established by the International Society for Heart and Lung Transplantation, patients considered for LTx were assessed and visited by all members of the lung transplant team. Inclusion on a waiting list was possible only upon the agreement of all members of the staff. Since then, almost 250 procedures have been performed, including some landmark procedures: the first bilateral procedure in 2003, the first pediatric transplant in 2006, the first split transplant in 2011 and the first transplant using the ex vivo lung perfusion (EVLP) technique in 2012. However, some problems persisted. Initially, simple preoperative monitoring and patient positioning were problematic and each transplant presented individualized challenges, illustrating the difficulties inherent in establishing routines in the operating room. However, over time, the program has achieved consistently satisfactory results and survival in line with international rates (Figure 1). For diseases such as cystic fibrosis, the survival to the end of the first year is over 90%, even higher than the ISHLT Resistries 11. Approximately 35 procedures are performed annually in the State of Sao Paulo - a modest number compared to the number of patients on the waiting list, which impacts on the mortality rate of patients on the list. The main reason for the low number of transplants performed is the low success rate of lungs obtained from multiorgan donors. It is estimated that only 5% of available lungs are used, a very low frequency compared to the average rate of 15% reported by the UNOS 12. The main reason for the low utilization is the quality of the available lungs, which are rejected more than 50% of the time due to infection or inadequate management resulting in loss of lung function 13. Figure 1 Kaplan-Meier Survival Curve of LTx patients. One year survival: 65.6%, Five years survival: 55.3% and Ten years survival: 43.7%. Improving the quality of available donor lungs seemed to be the best solution for increasing the number of transplants. Thus, the first report on the reconditioning of initially rejected donor lungs by ex vivo perfusion 14 presented a solution for this problem. In 2007 we began preparations for EVLP via training courses and experimental studies with lungs rejected for transplantation. We initially sought to establish our methodology 15,16, then tested lung preservation solutions 17 and static or continuous topical preservation methodologies 18. This prepared us to perform the first lung transplantation using EVLP in Brazil in 2012. Three years after the procedure, the first patient is doing well. However, the cost and quality of using EVLP donor tissue in our country, and as a result, other transplants have not been performed with this technique. New research has been implemented in this area that incorporated the use of broad spectrum antibiotics during EVLP 19 and in trachea transplantation 20,21. Two important issues remaining are the training of personnel and international recognition. All staff members were trained in our institution and completed the training in transplant centers in North America or Europe. The Ministry of Health has certified InCor for medical residency in pulmonary and surgical transplantation, as well as two years of training in a clinical or surgical fellowship in lung transplantation certified by the Ministry of Education. We are internationally recognized as a part of the ISHLT registry and we actively participate in international congresses as members of the society and through the submission of scientific papers. Institutional support is fundamental for the maintenance of staff and we were supported without fail throughout the formation of the transplant group. Although the number of transplants performed every month remains small, the need of these patients for care is intense. Thus, maintaining a professional team on a full-time basis will only be feasible with professional development and salary adjustments. In 2013, the Transplant Center Unit of InCor was created, which relies on a 24/7 nursing team fully dedicated to procuring thoracic organs and mediating and enhancing the work of the transplant teams, resulting in the realization of 98 transplants in 2014, including adult and pediatric heart transplants and lung transplants. The road traveled thus far has enabled the formation of an accomplished group and national leadership in this area. It is essential that the foundations of our group are the same as those of universities: care, teaching and research. We believe that we have achieved these goals, but much remains to be accomplished in this field.

Primary tumors of the heart are rare, with an incidence between 0.0017% and 0.19% in unselected patients at autopsy. Approximately 75% of the tumors are benign, and nearly half of them are myxomas (1) Atrial myxoma is the most common benign cardiac neoplasm, and its origin has been ascribed to a multipotential mesenchymal cell (2) Myxomas commonly occur between the third and sixth decades of life and are three times more frequent in women (3) There are two distinctive forms of the tumors: solid and ovoid myxomas and soft and papillary myxomas. Solid tumors are more likely to present with symptoms of congestive heart failure (CHF), while papillary tumors are more likely to embolize to the cerebral and other peripheral vessels (4) At the time of diagnosis, 92% of the patients have symptoms of CHF (5) Atrial myxoma may mimic valvular heart disease, cardiac insufficiency, cardiomegaly, bacterial endocarditis, disturbances of ventricular and supraventricular rhythm, syncope, and systemic or pulmonary embolism (3) The purpose of this paper is to present a case report of atrial myxoma mimicking severe mitral valve stenosis at cardiac auscultation and the importance of echocardiograpy in the diagnosis.

Thrombotic thrombocytopenic purpura (TTP) is a rare hematologic syndrome. It is a multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia and may be accompanied by fever and renal or neurologic abnormalities (1,2). Most adult patients acquire (3) the disease as a result of autoantibodies against ADAMTS13 (i.e., idiopathic TTP), or it is observed in association with collagen vascular disease, bone marrow transplantation, systemic sclerosis, infections, polymyositis, pregnancy, or drug treatment, including cyclosporine, tacrolimus, ticlopidine, and antineoplastic agents (i.e., non-idiopathic TTP) (1,4). However, TTP associated with mitral valve replacement surgery has not been reported. In this paper, we describe a case of a 41-year-old female who developed acute TTP after mitral valve replacement surgery. The patient was treated with plasma exchange (PE) and recovered following an uneventful course.

We read the paper titled “Acupuncture and exercise capacity: A case report” by Nascimento RC et al with great interest (1). The results of the study demonstrated that acupuncture is an efficient tool for improving the exercise capacity of an individual. However, some portions of the methodology remain unclear, and we would like to highlight some published data regarding the treadmill cardiopulmonary exercise test. Basically, a treadmill is a piece of equipment used to measure the status of the heart and is used as a diagnostic and prognostic measurement when the appropriate protocol is selected. We are interested in identifying the ramp protocol used by the authors. Additionally, it would be interesting to know whether the subjects completed the protocol before and after acupuncture treatment. For future case reports or studies, we suggest that the subjects recruited for a program to improve health and well-being need to undergo specific protocols, such as the Bruce or modified Bruce protocol, depending on the design of the exercise program (2). Commenting on the results, the authors reported that the patient showed improvement in his exercise capacity following acupuncture treatment. We would like to comment on the effect of the study on two types of clinical subjects. First, when the techniques are applied to neurological subjects (those paralyzed and semiconscious), oxygen consumption and other variables can improve. Similarly, when these techniques are applied to cardiac patients (those diagnosed as hypertensive), negative effects can occur. Physiologically, the amount of oxygen consumption may cause the heart to become stressed following acupuncture therapy. Under such conditions, the heart needs to pump more blood to cope with the demand, which may increase the heart rate and in turn increase blood pressure. Therefore, it can be said that the results of the study would be desirable for a particular population to increase exercise capacity when it is cautiouslxy used for patients with stable vital parameters. Overall, this is an interesting case report for discussion that may benefit individuals who attend a program to improve their well-being. The authors and the editor need to be applauded for highlighting such an innovative treatment for exercise capacity.

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, ...

As Clinics opens its sixth year of existence, its second as a monthly periodical, we shall be expecting our first posting of an Impact Factor by the ISI Journal of Citations report. Over this period, CLINICS gradually evolved from a publisher of articles originating mainly from the Medical College of Sao Paulo University to a more cosmopolitan Brazilian and International publisher of science. This trend, illustrated in Fig. 1, strongly suggests that the posting of our first impact factor will enhance the trend towards a truly cosmopolitan journal. In this issue, we publish eight Clinical Science reports. Hovnanian et al. endeavored to determine long-term survival, identify preoperative factors predictive of a favorable outcome, and assess functional improvement after coronary artery bypass grafting in 244 patients with advanced left ventricular dysfunction and found that for selected patients with severe ischemic left ventricular dysfunction and predominance of tissue viability, coronary artery bypass grafting it may be possible to implement preoperative clinical/functional parameter measurements for predicting outcome, such as left ventricular ejection fraction and gated left ventricular ejection fraction at exercise or at rest. Tiryakioglu et al. examined the frequency of Cushing’s syndrome (CS) in 150 obese patients devoid of specific clinical symptoms of Cushing’s syndrome and found that a significant proportion (9.33%) of patients with simple obesity had Cushing’s syndrome; they argue that obese patients should be routinely screened for Cushing’s syndrome. Barbosa et al. propose to improve the transmission of information between requiring physicians and radiologists by means of a structured report for thyroid sonography developed according to information gathered from radiologists and endocrinologists working in the field. They found that implementation of the structured report in a university hospital was viable, and that radiologists and endocrinologists preferred the structured report when compared to free text, and both agreed that the former improved the transmission of information. Dantas et al. evaluated the kinetics with which a cholesterol-rich emulsion (called a low-density emulsion) binds to low-density lipoprotein receptors in a group of 10 patients with grade III obesity, versus 10 non-obese healthy control individuals by the fractional clearance rate, and found that grade III obese subjects exhibited normal low-density lipoprotein removal from plasma as tested by the nanoemulsion method, but triglyceride removal was slower. Horasanli et al. compared the efficacy of combined lumbar plexus-sciatic nerve blocks versus epidural anesthesia in 40 patients per group undergoing total knee surgery, and found that the lumbar plexus-sciatic nerve blocks provide effective unilateral anesthesia and may offer a beneficial alternative to epidural anesthesia in patients undergoing total kneesurgery. Scorleze-Ferrer et al. examined causes of admission in the public health system for children from zero to nine years of age in the city of Sao Paulo during the years 2002 to 2006 and compared these results to those from the national data, and found a paradoxical increase in the number of hospitalizations during an expansion of primary attention, indicating that the rise was not associated with a significant improvement in the quality of service. Ramos et al. determined differences in cardiac vagal tone values in non-obese healthy, adult men with and without unfavorable anthropometric characteristics, and found that non-obese and healthy adult men with unfavorable anthropometric characteristics tend to present lower cardiac vagal tone levels. They claim that early identification of this trend by simple protocols that are non-invasive and risk-free, using select anthropometric characteristics, may be clinically useful in a global strategy to prevent cardiovascular disease. Melotti et al. evaluated the value and limitations of clonality analysis in the diagnosis of primary cutaneous B-cell lymphomas (PCBCL) and B-cell pseudolymphomas (B-PSL). The study included 29 cases of B-cell lymphoproliferative processes classified as primary cutaneous B-cell lymphomas (13), B-PSL (6) and inconclusive cases (10) using histology and immunohistochemistry, and concludes that the use of the two protocols, IgH FR3-trad and IgL-Kappa (IgL-K) Biomed protocols for clonality analysis improved diagnostic accuracy. We also publish four Basic Science papers Morais Silva et al. analyzed the effects of fluoxetine, a selective serotonin re-uptake inhibitor, on the enamel organ of rats and found no structural changes in the experimental group compared to the controls, suggesting that, at the dose used, fluoxetine did not interfere with serotonin-mediated development of the enamel organ or the process of amelogenesis. Sallum et al. evaluated transcapillary refill in a model of retroperitoneal uncontrolled, treated hemorrhage in dogs and concluded that despite the rebleeding observed in treated groups, the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation, producing evident transcapillary refill, while the Lactated Ringer’s solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage. Subhash et al. describe the normal and variant anatomy of the coronary artery ostia in Indian subjects and find that the preferential location of the ostia was within the sinus and above the cusps, but below the sinutubular ridge. On occasion, normal variants such as multiple ostia, vertical or circumferential shift in the position, and slit-like ostia may create confusion in interpreting the images and pose a difficulty during procedures like angiography, angioplasty, and coronary artery bypass grafting. Norhazlia et al. describe the effect of eurycoma longifolia on spermatogenesis in estrogen-treated adult male rats and claim that the extract acts as a potential agent for reversing the effects of estrogen by increasing spermatogenesis and sperm counts in rats after fourteen consecutive days of treatment. We also publish a review on coronary heart disease in women and 3 case reports.

INTRODUCTION Scrotal gangrene has been described as a necrotizing fascitis and it is most often caused by polymicrobial infections. This paper describes an unusual case of gangrene secondary to an aggressive testicular cancer with an excellent response to chemotherapy. […] Testicular tumor presenting as scrotal gangrene

Despite the well-known valuable role of necropsies in pathology training and their indisputable importance for quality assurance in medical practice, the number of necropsies performed worldwide has decreased over the last few years. This has been ascribed, in part, to the idea that, at the time of death, most diagnoses have already been made using new diagnostic technologies, including clinical, morphological, and molecular pathology and imaging methods. In CLINICS 2008;63(5):581–8, Kotovicz et al.1 compared necropsy and clinical diagnosis at our large teaching hospital, where, although still performed, the number of necropsies has also declined. Unexpectedly, major missed diagnoses, which could have led to a change in management with increased survival or cure, were detected in 16.3% of cases. Minor diagnoses not directly related to the cause of death were detected in an additional 28.1% of cases. In a similar study at the Heart Institute of the same hospital, Saad et al.2 also found major disagreements regarding the cause of death in 30.0% of cases in a sequential series of 406 necropsies, mostly involving cardiovascular and respiratory diseases. In both articles, the authors quoted other studies from different hospitals and countries, and found that, although new technological tools had indeed diminished the differences between clinical and necropsy findings, major diagnostic discrepancies were found in 14 – 39% of cases, even in recent series from developed countries3–6. These papers highlight the occurrence of remarkable diagnostic failures, with important consequences for patient management. One reason for the decline in autopsy rates seems to be family concern about the procedure. In the United Kingdom, this concern arose mainly after the revelation of unauthorized organ retention7. In Brazil, and possibly in other countries, there is a cultural desire that burials occur promptly, and families will not often consent to necropsies because of the delay caused by the procedure. Given this, pathology departments should try to decrease such delays as much as possible. However, at the Heart Institute, where for several years families were asked to consent to an autopsy upon hospital admission, the percent of family authorization (~60%) was much higher than the actual necropsy rate (~25%), indicating that, in many cases, even when consent is granted, physicians did not request a necropsy. Thus, it seems reasonable to question what has caused this lack of physician interest. Some reasons might include: a desire to avoid ethical or legal problems that might arise if any kind of error or disagreement was found between the clinical and necropsy findings, procedural costs, or the perception that, with the presently available technology, there is little to be revealed by postmortem examination. Although this last idea is clearly contradicted by the articles of Kotovicz et al.,1 Saad et al.,2 and others quoted in those studies, it deserves further consideration. Necropsy results extend beyond individual cases. Even when one necropsy does not reveal any new findings, it may be performed as part of a study and thereby help identify morphological traits of diseases not readily apparent in individual patients. This scenario is exemplified by the fact that most cases of cardiac amyloidosis are still diagnosed only at necropsy8. Furthermore, despite advances in image analysis and other methods, pulmonary embolism, endocarditis, and the initial phases of bronchopneumonia cannot currently be definitively diagnosed using imaging techniques alone7,8. Virtopsy9, which is a method of postmortem examination involving magnetic resonance imaging or tomography studies of a corpse, along with needle sampling, would probably also be of little help in many cases. In a recent comment on the reasons behind the apparent diminution by physicians of the importance of necropsy, Pompilio and Vieira10 stated that this loss of interest might be related to the increasing influence of technological tools in the practice of medicine. Indeed, the very concept of disease may be changing. In the past, nearly all conditions, except psychiatric disorders, were defined based on morphological pathology. Today, our understanding of disease and disease treatment is further enhanced by information related to genetic polymorphisms, cell counting, gene expression profiling, proteomics, and a type of “new-humoral” medicine involving knowledge concerning cytokines and many other circulating molecules. Most of these new techniques should be major tools in the modern pathology laboratory, with each approach contributing to a more complete concept of disease. For example, a single disease might be linked to a number of different genetic polymorphisms affecting the production, destruction, or pre- or post-translational modification of a single protein. Similarly, the term “inflammatory” infiltrate is no longer sufficient; the effect of such an infiltrate can depend on the subtype and functional status of each cell present, as some cell types modulate inflammation in a number of ways. On the other hand, imaging tools represent a large proportion of newly available instruments. Their increasing importance reinforces the fact that morphologic pathology is still pivotal to diagnosis and to the definition of many diseases. Except for situations in which movements or flows are required, all of these instruments attempt to examine, while the patient is still alive, alterations in human organs and cells that were previously detected only at necropsy. This suggests that necropsy remains the gold standard for diagnosis. For instance, the term “virtual histology” appears in 77 articles found via PubMed, 64 concerning intravascular ultrasound, 10 on confocal laser endoscopy of the gastrointestinal tract, and 3 relating to other organs. As demonstrated in the article by Mauad et al.1, as well as others, significant differences still exist between virtual and real pathology. Therefore, in our opinion, teaching hospitals should strive to perform necropsies for 100% of in-hospital deaths. Only family denial should prevent the performance of these procedures, and efforts should be made to decrease the number of such cases. In conclusion, we believe that improved accuracy of new diagnostic methods could be achieved through closer collaboration between clinicians, radiologists, and clinical and surgical pathologists. In many hospitals, including Hospital das Clinicas-FMUSP, such integration is rapidly growing within most sub-specialties (the most notable being fine-needle aspiration), yielding, in certain clinical contexts, major improvements in accuracy. Within this type of framework, necropsies will remain the gold standard for the multi-specialty approach to diagnosis and will guide us in the safe and optimal use of the present and future diagnostic armamentarium.

There may be many reasons for the malfunctioning of transplanted organs. Percutaneous biopsy can easily be undertaken to give greater specificity to possible immunological causes of rejection.1,2 Acute venous or arterial thrombosis frequently leads to graft loss after a short period of anuria which justifies a diagnosis of vascular occlusion. This causes graft dysfunction or loss in 3.5% to 12.5% of cases.3,4 Progressive malperfusion with rising or stabilized serum creatinine at higher levels demands aggressive imaging investigation to exclude possible aneurismal formation, progressive stenosis, or vascular fistula. This paper reports a rare case of kinking of the main artery due to organ rotation occurring after a simultaneous pancreas-kidney transplant.

This April 2007 issue of CLINICS highlights a paper by Giribela et al, who measured the effects of a low-dose oral contraceptive (15 ¼g ethinyl estradiol/60 ¼g gestodene) on venous endothelial function of 20 healthy young women in a prospective case control study. Venous endothelial function was evaluated at baseline and after 4 months in the oral contraceptive users group (11 women) and in a control group (9 women). After preconstriction of the vein with phenylephrine, dose-response curves for acetylcholine [...]

In this third issue of CLINICS, we highlight a study on the epidemiology of AIDS, with special interest in the prevention of vertical transmission during pregnancy. Brazil has become a trend setter for the control of AIDS in a developing country and we believe that the highlighted paper is further contribution to this issue. Our electronic editing is now operational and we strongly invite future contributors to register and submit their articles online (www.mdview.com.br/clinics) since this has enhanced the speed [...]

Dear Editor, We read with deep interest the paper “Evaluation of the mean platelet volume in patients with cardiac syndrome X” by Demirkol et al. (1). The authors (1) aimed to evaluate the mean platelet volume (MPV) in patients with cardiac syndrome X (CSX) and compare patients with coronary artery disease (CAD) with a control group. We have a minor criticism concerning their methodology. Although statistical significance was defined as p

Dear Editor, We read with great interest the article by Bueno Filho et al. entitled “Rare association of cutaneous vasculitis, IgA nephropathy and antiphospholipid antibody syndrome with tuberculous lymphadenitis” that was published in the esteemed journal Clinics. The authors presented an interesting case of cutaneous vasculitis, IgA nephropathy and antiphospholipid antibody syndrome with tuberculous lymphadenitis in a 45-year-old woman (1). I would like to mention a few points regarding this paper. A definitive pathologic IgA nephropathy diagnosis based on immunostaining assays requires the presence of dominant mesangial IgA depositions in the absence of significant C1q depositions to rule out lupus nephritis (2–5), which the authors should note. Moreover, the detection of significant fibrin deposition along with IgA deposits can help differentiate between primary IgA nephropathy and Henoch-Schonlein purpura nephropathy (2–5). Therefore, the authors should also discuss this point. Bueno Filho et al. classified the morphologic lesions of IgA nephropathy in renal biopsies as “focal and segmental sclerosis with mild focal and chronic tubulointerstitial damage”. Indeed, as a result of the publication of the Oxford classification of IgA nephropathy in 2009 (2,5), it is necessary to describe the morphologic lesions of IgA nephropathy according to this classification system (6–8). Furthermore, figure 2C shows a normal glomerulus, which is in contrast to the described morphologic features. The authors reported the final diagnosis as a combination of tuberculous lymphadenitis, cutaneous leukocytoclastic vasculitis, primary IgA nephropathy and anti-phospholipid antibody syndrome. However, the presence of morphologic lesions upon renal biopsy suggests anti-phospholipid syndrome nephropathy and should have been reported (9–11). Anti-phospholipid antibody syndrome is a vaso-occlusive disease (12,13) that affects renal tissue and has various morphologic lesions, some of which are characteristic of the disease (14). Accurate documentation and reporting of such rare cases are necessary to determine the complete spectrum of this disorder and improve the understanding of its pathophysiology. Bueno Filho et al. merit compliments for bringing this interesting case to this journal for discussion. Such discussions may help increase awareness of anti-phospholipid antibody syndrome among pathologists and nephrologists, particularly in developing countries.

Dear Editor, We greatly enjoyed reading the thought-provoking article by Lopes et al. in a recent issue of your esteemed journal (1). Interestingly, in recent years, data have emerged regarding a role for EML4 (echinoderm microtubule-associated protein-like 4)–ALK (anaplastic lymphoma kinase) in personalized treatment for advanced non-small-cell lung cancer (NSCLC) (2,3). EML4-ALK undergoes constitutive dimerization through the interaction between the coil-coil domains within the EML4 region of each monomer, thereby activating ALK and promoting oncogenic activity (4). EML4-ALK fusion, EGFR, and KRAS mutations are all mutually exclusive, implicating ALK rearrangement as a potential therapeutic target in EGFR wild-type and KRAS wild-type lung cancers (5). Nevertheless, Lopes' study (1) raises some interesting questions. Was patient selection for the study carried out appropriately? Did the study provide a representative sample of the Latin-American population, as described in the paper? Could immunohistochemistry be substituted for fluorescence in situ hybridization? Which technique is more appropriate for clinical practice? Should we perform this analysis in a specific subset of patients or in all advanced NSCLC patients? In addition, it is interesting to speculate whether EML4-ALK-targeted therapies may be relevant for clinicians, although patients positive for the EML4–ALK fusion protein frequently present at an advanced clinical stage, and their tumors demonstrate a solid adenocarcinoma pattern and signet ring cells (5). Furthermore, the presence of the EML4-ALK fusion oncoprotein is associated with nonsmokers or light smokers and is more frequent in younger patients (5). Thus, young, non-smoking patients and patients with adenocarcinoma tumor histology may indeed benefit from an EML4-ALK diagnostic test. Recently, the U.S. Food and Drug Administration approved crizotinib, which is a small-molecule inhibitor of the ALK tyrosine kinase, as a treatment for patients with locally advanced or metastatic NSCLC expressing the EML4–ALK fusion protein (2). The results were recently reported for a clinical trial in which 82 ALK-positive patients were evaluated for the therapeutic efficacy of crizotinib (6). The results were quite promising, demonstrating an overall response rate of 57% (46 partial responses and 1 complete response) and a 33% stable disease rate (27 patients) (2). Of the 82 patients, 63 (77%) continued to receive crizotinib at the time of data cut off, and the estimated probability of a 6-month progression-free survival was 72% (2). Thus, the refined understanding of the NSCLC molecular profile described over the last decade has proven to be an important tool to help medical oncologists develop new approaches for NSCLC treatment. Despite the small frequency of advanced NSCLC patients who present with EML4-ALK fusion (2.4 to 6.7%) (1), we believe that all patients in this setting should have the opportunity to receive such innovative therapies and approaches. However, further studies are warranted to establish the appropriate pharmaco-economic profiles.

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

Many years ago, we published the first report in the literature of a patient having infected pancreatic necrosis who survived following strictly medical therapy, namely antibiotics. 1 That paper was harshly criticized, perhaps rightly so, since conventional wisdom recommended—and to some extent still advises—open necrosectomy and drainage for nearly 100% of such patients. 2 It should however be noted that, in that case, administering only antibiotics was neither a simple option, nor an unauthorized experiment, for the very good reason that the patient himself irrevocably refused any surgical intervention on religious grounds. Even at that time, experienced surgeons in international congresses would privately concede that every once in a while they had come across this situation: nonoperated patients who had survived on antibiotics only, but publication of such results was generally regarded as an anathema. Fifteen years and several articles later, infected pancreatic necrosis has not become a trivial disease – and probably never will – nor has conservative therapy become mainstream. However, advances in interventional radiology and other forms of minimally invasive management have greatly benefited patients with deep-seated infected foci in general, including those associated with severe pancreatitis. 3,4 Of course, minimally invasive management is not the gold standard for infected pancreatic necrosis, and open surgical debridement of contaminated foci still produces the most reliable results, with present reported mortalities of 20% to 25%. 2,5 However, the use of minimally invasive

In this issue of Clinics, we highlight a paper by Nakano et al, who describe a new stress test using isokinetic dynamometry for the evaluation of the functional limitation caused by occlusive arterial disease in upper limbs. Twenty three patients with subclavian arterial occlusion were compared to 23 patients of similar age exhibiting non-occlusive arterial pathologies. This test allows for a better choice of therapeutic approach for each and report on the objective parameters that allow comparisons of the results [...]