Evidence-Based Classification for Post-bariatric Weight Regain from a Benchmark Registry Cohort of 18,403 Patients and Comparison with Current Criteria.

INTRODUCTION: There is a need for a standardized, evidence-based classification of post-bariatric weight-regain, to investigate and compare revision procedures and to advice and treat patients in an evidence-based way. METHODS: We used standard deviations (SD) of the highest (1-2 years) and latest (> 2 years) percentage total weight loss (%TWL) results after primary bariatric surgery from the Dutch Audit for Treatment of Obesity (DATO) bariatric registry as benchmarks for (above) average (≥ - 1SD), poor (- 1SD to - 2SD) and insufficient (< - 2SD) weight loss. Weight regain maintaining (above) average weight loss was called grade 1, weight regain towards poor weight loss grade 2, towards insufficient weight loss grade 3, with subgrades 2a/3a for below average weight loss from the start, and 2b/3b for weight regain from (above) average to below average weight loss. Patient characteristics and diabetes improvement/impairment were compared. Sensitivity and specificity of 14 existing weight regain criteria were calculated. RESULTS: We analyzed 93,465 results from 38,830 patients (77.1% gastric bypass, 22.5% sleeve gastrectomy). The - 1SD thresholds for early and late weight loss approximated 25%TWL and 20%TWL, the - 2SD threshold for late weight loss 10%TWL. Weight regain could be analyzed for 18,403 patients (2.5-5.2 years follow-up). They regained mean 6.7 kg (5.4%TWL), with 66.8% grade 1 weight regain, 7.2% grade 2a, 7.4% grade 2b, 2.1% grade 3a, and 0.6% grade 3b. There were significant differences in comorbidities, gender, age, weight regain, diabetes impairment, and diabetes improvement across grades. Weight regain criteria from literature were extremely divers. None had high sensitivity. CONCLUSION: The DATO classification for post-bariatric weight regain combines the extent of weight regain with evidence-based endpoints of weight loss. It differentiated weight regain maintaining (above) average weight loss, two intermediate grades, gradual weight regain with below average weight loss from the start (primary non-response) and steep weight regain towards insufficient weight loss (secondary non-response). The classification is superior to existing criteria and well supported by evidence.

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations.

BACKGROUND: Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation. METHODS: In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up. RESULTS: Changes in biventricular dimensions were assessed in 163 Marfan patients (48 % female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. -8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. -18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. -8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. -7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28). CONCLUSION: Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

The revised role of TGF-ß in aortic aneurysms in Marfan syndrome.

BACKGROUND: Recently, we demonstrated that losartan reduced the aortic root dilatation rate (AoDR) in adults with Marfan syndrome (MFS); however, responsiveness was diverse. The aim was to determine the role of transforming growth factor-ß (TGF-ß) as therapeutic biomarker for effectiveness of losartan on AoDR. METHODS: Baseline plasma TGF-ß levels of 22 healthy controls and 99 MFS patients, and TGF-ß levels after 1 month of losartan treatment in 42 MFS patients were measured. AoDR was assessed by magnetic resonance imaging at baseline and after 3 years of follow-up. RESULTS: Patients with MFS had higher TGF-ß levels compared with healthy controls (121 pg/ml versus 54 pg/mL, p = 0.006). After 1 month of therapy, losartan normalised the TGF-ß level in 15 patients (36%); the other 27 patients (64%) showed a significant increase of TGF-ß. After 3 years of losartan therapy, patients with a decrease in TGF-ß had significantly higher AoDR compared with patients with increased TGF-ß (1.5 mm/3 years versus 0.5 mm/3 years, p = 0.04). Patients showing a decrease in TGF-ß after losartan therapy had significantly elevated baseline TGF-ß levels compared with patients with increased TGF-ß (189 pg/ml versus 94 pg/ml, p = 0.05). CONCLUSION: Patients responding to losartan therapy with a reduction of the plasma TGF-ß level had higher baseline TGF-ß levels and a higher AoDR. Most likely, TGF-ß levels may be considered to be a readout of the disease state of the aorta. We propose that increased angiotensin II is the initiator of aorta dilatation and is responsible for increased TGF-ß levels in MFS. The concept of TGF-ß as initiator of aortic dilatation in MFS patients should be nuanced.

Long-term outcome of superficialis-to-profundus tendon transfer in patients with clenched fist due to spastic hemiplegia.

BACKGROUND: Spastic hemiplegia is a common feature after stroke, which can result in a clenched fist deformity with secondary hygienic problems and pain. Operative treatment can improve these problems, although literature about its long-term effects is lacking. PURPOSE: To determine whether Superficialis-to-Profundus tendon (StP-) transfer procedure leads to permanent improvement of hygiene and reduction of pain in patients with clenched fist due to spastic hemiplegia following stroke. METHOD: Patients who underwent a StP-transfer in 2003-2005 were evaluated on skin condition, upper extremity joint mobility, resting position and muscle tone and with VAS scores on hygiene maintenance and pain in the hand. RESULTS: Six patients (mean age 54 years; duration after stroke 10 years) were included. Indications to operate were hygienic problems only (3) or combined with pain (3). The average follow-up period was 19 months. After 6 weeks of post-operative splinting, no standard follow-up was applied. Serious post-operative complications were not reported. At follow-up no hygienic problems were present and pain was decreased in all except one patient. All hands could passively be fully opened. In resting position, flexion was seen in the MCP-joints (60-90 degrees). Muscle tone was raised in flexors of the wrist and fingers and m. adductor pollicis (Ashworth 1-2). Given the same pre- and post-operative circumstances, all patients would agree to have the surgery over again. CONCLUSION: Even 19 months after the StP-transfer for clenched fist, all operated hands could still be fully opened and there was a permanent improvement of hygiene and pain reduction.

Immunologic evaluation in infective endocarditis.

OBJECTIVE: To analyze the immune response in peripheral blood of patients with infective endocarditis. METHODS: We studied 10 patients with infective endocarditis, age range from 20 to 50 years-old, males and females, and 20 healthy subjects in the same age range. The diagnosis of the disease was based on the clinical picture, echocardiogram, and hemoculture based upon samples drawn and tested before the treatment started. The were no history of atopy or malnutrition, no autoimmune disease, and they were not using any immunosuppressant or antibiotic medication. RESULTS: The patients with endocarditis had significantly higher T and B lymphocyte, CD4+ and CD8+ cell counts, IgM and IgG serum levels, and C4 component of the complement than the control group; no significant difference concerning serum IgA and neutrophil oxidative metabolism; a significant decrease in C3, chemotaxis, and monocyte phagocytosis;cryoglobulins were detected in 66.6% of patients and they were formed by IgG, IgM, IgA, C3, and C4. CONCLUSION: The patients with infective endocarditis were immunocompetent in most sectors of immune response and, at a certain moment, an autoimmune component may be present.

Effect of vascular freezing on the histopathology of dissected small vessels in the rat: vascular freezing does induce intimal hyperplasia in arteries and veins.

Intimal hyperplasia is the primary response of a vessel wall after injury. It may be the single most significant factor affecting long-term patency. The purpose of this study was to find out whether freeze injury, inflicted on rat microvessels, would be followed by intimal hyperplasia. Toward this aim, we exposed the superficial femoral vessels in the rat. On one side they were frozen using liquid nitrogen spray. The other side was dissected as the control. Vessel segments, harvested immediately and after 1, 2, 3, and 5 months, were studied light microscopically for the occurrence and content of intimal hyperplasia. In the arteries a considerable intimal hyperplasia was found within a 4-week interval, persisting for at least 5 months, as a result of the freeze injury. In the veins, the intimal hyperplasia was much less marked but was nevertheless demonstrable. These findings are not in agreement with earlier studies, in which freezing of injured rat microarteries with liquid nitrogen spray was followed by complete regeneration of the vessel wall, without intimal hyperplasia taking place. The factors contributing to these differences are discussed. It is concluded that freezing of a vessel wall is followed by intimal hyperplasia, which is part of the normal healing process.

[Iatrogeny in cardiology]. / Iatrogenia em cardiologia.

The word iatrogeny derives from the Greek and concerns any disorder caused to the patient by inaproppriate medical practice. Unfortunately, the rise of an iatrogenic disease is related to the daily handline of cardiac disease. There are two types of iatrogeny: that caused by a medical action and omission iatrogeny, caused by the lack of a medical action. Iatrogeny occurs in all steps of medical practice starting with the patient-doctor relationship including diagnosis treatment and finally prevention of diseases. This article makes a brief commentary about iatrogenic heart disease and mentions some examples of it.

Pseudo-myocardial infarction during an episode of herpes zoster.

The patient arrived at the emergency unit with a history of acute myocardial infarction, for which she was treated. Without improvement in the pain, the patient developed heart failure and underwent a hemodynamic study, which showed normal coronary arteries and extensive ventricular impairment. During evolution, the clinical findings improved and herpes zoster appeared on the right shoulder. In a few months the clinical findings subsided, and the findings of the electrocardiogram, chest X-ray, and ventricular function were normal. The patient is currently asymptomatic.

Impact of second harmonic imaging on the determination of the global and regional left ventricular function by 2D echocardiography: a comparison with MIBI gated SPECT.

AIMS: To evaluate the impact of second harmonic (SH) compared to fundamental mode (FM) imaging on the echocardiographic determination of ejection fraction (EF) and wall motion score index (WMSI), using MIBI gated SPECT as an independent reference. METHODS: Sixty-two consecutive patients underwent an echocardiography study and a MIBI gated SPECT over 24 hours. EF was estimated visually (estimated-E) and was calculated with the Simpson biplane method (Tracing-T), for both FM and SH. WMSI was determined by two independent echo-readers blinded to the nuclear imaging results. The same segmentation and scoring system was used for WMSI determined by MIBI gated SPECT. RESULTS: The percentages of unscored segments because of suboptimal endocardial border detection were 19.5% (FM) and 9.0% (SH). The correlation coefficients (r) between SPECT-EF and echo-EF were: FM (E)=0.705, FM (T)=0.546, SH (E)=0.771, SH (T)=0.743. Agreement between SPECT-EF and echo-EF was acceptable for both imaging modalities (mean of the difference +/- 2 S.D.): -2.8 +/- 18.5 (FM) and -3.5 +/- 16.4 (SH). Correlation coefficients (r) between WMSI calculated by SPECT and by echo were 0.715 (FM) and 0.789 (SH). Agreement between SPECT-WMSI and echo-WMSI was good for all imaging modes but better with SH compared to FM: 0.12 +/- 0.91 (FM), 0.10 +/- 0.77 (SH). The interobserver correlation coefficients (r) for the WMSI were 0.939 (FM) and 0.996 (SH). The agreement between the two observers was better for SH compared to FM. The systematic differences (mean differences) were 0.21 (FM) and -0.01 (SH), and the random differences between both observers (2 S.D.) decreased from 1.55 (FM) to 0.29 (SH). CONCLUSIONS: The use of SH echocardiography decreases the number of unscored segments. This results in an important gain in correlation and agreement for EF determination between echo and SPECT, and in a considerable decline of the interobserver variability for the echo-determined WMSI. WMSI determined by MIBI gated SPECT correlated closely with the SH WMSI, and agreement between both methods was excellent.

Microcirculatory changes following different temperature washouts in a free flap model.

In spite of the extensive experimental work on vascular washout in free flap surgery, an optimal temperature for the washout solution has not been established. This study was designed to determine the effect of the washout solution temperature on the degree to which the microcirculation is cleared of blood. The cremaster muscle flap in the rat was used, in which the microcirculation can be directly viewed and the presence of blood and perfusion parameters within various vessels can be measured during and after washout. Washout was started with a single, high-pressure infusion and continued at 130 mmHg for 15 minutes. The temperature of the washout solution was either 2-3, 20-22, or 35 degrees C. In all three groups, washout cleared the microcirculation almost completely within the first minute. However, we observed that a cold or room temperature washout cleared the microcirculation more completely than a warm washout did. The temperature of the washout solution did not effect post washout capillary perfusion and/or arterial diameters.

Do leukocytes contribute to impaired microvascular tissue perfusion after arterial repair?

Impaired capillary perfusion may result in flap failure. Platelet emboli, polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free flap model. PMN concentrations were depleted using antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were isolated on a single neurovascular pedicle and after a simulated technically poor arterial anastomosis upstream and reperfusion, capillary perfusion was measured each hour for 6 hours. Even though the number of PMNs was significantly reduced in the animals treated with antineutrophil serum, capillary perfusion was not changed compared with controls. These results demonstrate that depleting circulating PMNs does not protect capillary perfusion in our model. These findings suggest that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.

Estudo multicêntrico de idosos em ambulatórios de cardiologia e geriatria de instituiçöes brasileiras / Multicenter study of elderly patients in outpatient clinics of cardiology and geriatric brazilian institutions

OBJETIVO - Avaliar aspectos epidemiológicos, clínicos e terapêuticos de idosos com doenças cardiovasculares (DCV), no Brasil. MÉTODOS - Idosos com DCV, atendidos em 36 serviços de Cardiologia e Geriatria do Brasil, foram investigados através de questionário aplicado aos que tinham consulta marcada para o período analisado (um mês). RESULTADOS - Estudados 2196 idosos de 65 a 96 anos, sendo 60 'por cento' mulheres e analisados od fatores de risco: sedentarismo (74 'por cento'), pressão arterial (PA) elevada (53 'por cento'), LDL colesterol aumentado (33 'por cento'), colesterol total aumentado (30 'por cento'), obesidade (30 'por cento'), HDL -colesterol diminuído (15 'por cento'), diabetes (13 'por cerno') e tabagismo (6 'por cento'). Observou-se maior prevalência nas mulheres, com três ou mais fatores de risco. O principal motivo de consulta foi a PA elevada (48 'por cento'). Teste ergométrico e cinecoronariografia, foram mais solicitados para os homens. Os diagnósticos mais comuns foram hipertensão arterial sistêmica (HAS) (67 'por cento') e insuficiência coronária (iCo) (29 'por cento'). Os medicamentos mais utilizados foram diuréticos (42 'por cento'). CONCLUSÄO - Foi observada alta prevalência de fatores de risco (93 'por cento'), principalmente nas mulheres; sedentarismo, como fator de risco mais freqüente, aumentando de prevalência com a idade; HAS, como principal motivo de consulta e diagnóstico; menor investigação e diagnóstico de iCo em mulheres; diuréticos, como os fármaco mais freqüentemente prescritos; insuficiência cardíaca como principal doença associada a internação (31 'por cento') e atendimento de emergência (10 'por cento').

Lack of nitric oxide contributes to vasospasm during ischemia/reperfusion injury.

Vasospasm can be a complication after free tissue transfer and replant operations. Recent studies suggest that vasospasm may be due to endothelium dysfunction, resulting in impairment of nitric oxide production. The present experiment was designed to investigate acute responses of the microcirculation of skeletal muscle to local interarterial infusion of sodium nitroprusside (a direct donor of nitric oxide and thus an endothelium-independent vasodilator) or acetylcholine chloride (which stimulates endothelium release of endogenous nitric oxide) during reperfusion after 4 hours of warm ischemia. Male Sprague-Dawley rats, each weighing 100 to 120 gm, were anesthetized with sodium pentobarbitone and were surgically prepared with vascular isolated and denervated cremaster muscles that were subjected to 4 hours warm ischemia and 2 hours of reperfusion. Sodium nitroprusside (10(-3) M), acetylcholine chloride (10(-4) M), or normal saline (eight rats for each group) were administered by local infusion (0.1 ml/hour) through the femoral artery into the natural blood flow of the cremaster. The arterial tree in the cremaster was observed and arteriole diameters (A1-A4) were measured using intravital microscopy. The number of arteriole branches having temporary stoppage of flow were counted in each cremaster. The results from this study show that local infusion of sodium nitroprusside, but not acetylcholine chloride, prevents ischemia/reperfusion vasoconstriction in A3 and A4 arterioles and thus improves microvascular blood flow. Generalized vasoconstriction caused by topically applied norepinephrine (10(-6) M) to sham ischemia cremasters could be completely reversed by the local infusion of 10(-4) M acetylcholine chloride. These results indicate that vasospasm after ischemia/reperfusion may be related to temporary endothelial cell dysfunction, resulting in the inability to produce sufficient nitric oxide during early reperfusion. Vascular smooth muscle, however, is responsive to locally administered sodium nitroprusside infusion (which is thought to provide exogenous nitric oxide).

Effect of low dose aspirin on thrombus formation at arterial and venous microanastomoses and on the tissue microcirculation.

In free flap/replantation surgery, failure is usually associated with thrombotic occlusion of a microvascular anastomosis (risk zone I) or, on occasion, flow impairment in the microcirculation of the transferred or replanted tissue (risk zone II). The objective of this study is to describe the effect of low dose aspirin on blood flow at both risk zones in microvascular surgery. Risk zone I: In rat femoral arteries and veins, thrombus formation was measured at the anastomoses using transillumination and videomicroscopy. Forty male Wistar rats were assigned in equal numbers to four groups: either arterial or venous injury with either aspirin (5 mg/kg systemically) or saline treatment. We found that aspirin significantly reduces thrombus formation at the venous anastomosis (p = 0.001). Risk zone II: In the isolated rat cremaster muscle downstream from an arterial anastomosis, we measured capillary perfusion, arteriolar diameters, and the appearance of platelet emboli for 6 hours in the muscle microcirculation. Sixteen male Wistar rats in two equal groups received either aspirin (5 mg/kg systemically) or saline. We found that in aspirin-treated animals, capillary perfusion is significantly (p = 0.002) improved, whereas arteriolar diameters and emboli only slightly increased. In conclusion, low dose aspirin inhibits anastomotic venous thrombosis and improves microcirculatory perfusion in our rat model. These studies provide quantitative data confirming and clarifying the beneficial effects of low dose aspirin in microvascular surgery.

[Multicenter study of elderly patients assisted at outpatient cardiology and geriatrics clinics in Brazilian institutions]. / Estudo multicêntrico de idosos atendidos em ambulatórios de cardiologia e geriatria de instituições Brasileiras.

PURPOSE: To evaluate epidemiological, clinical and therapeutic aspects of elderly patients with cardiovascular disease in Brazil. METHODS: Elderly patients with cardiovascular disease treated in 36 centers of cardiology and geriatrics were investigated through a questionnaire applied to those who had an appointment during the analyzed period. RESULTS: 2196 elderly patients ranging from 65 to 96 years of age were analyzed, 60% of which were females. The main risk factors were: sedentarism (74%); high blood pressure (53%), high LDL-cholesterol (33%), high total cholesterol (30%), obesity (30%), low HDL-cholesterol (15%), diabetes (13%) and smoking (6%). A higher prevalence of females existed among those with > or = 3 risk factors. The main reason for the medical appointment was high blood pressure (48%). Stress test and coronariography were requested more often in males. The most common diagnoses were hypertension (67%), and coronary disease (29%). The most often used medications were diuretics (42%). CONCLUSION: There was high prevalence of risk factors (93%), mainly in females; sedentarism was the most common risk factor and prevalence increased with age; hypertension was the most common reason for a medical appointment. Diuretics were the most used drugs; congestive heart failure was the main disease associated to hospitalization (31%) and emergencies (10%).

Anatomy of the feeding blood vessels of the cremaster muscle in the rat.

Since the early seventies over 300 studies have used the cremaster muscle as a flap model, yet little has been reported on the upstream feeding vessels of this muscle. The purpose of this study was to investigate the anatomy of the cranial feeding vessels of the left and right cremaster muscle in Sprague-Dawley rats. An additional aim was to compare these results with the anatomy of the feeding vessels of the cremaster muscle in another strain (Wistar). To permit identification of the cranial feeding vessels, the pedicle was dissected very carefully and thereafter perfused with green dye, which was administered through a cannula placed in the distal femoral artery. In Sprague-Dawley rats it was found that the cremaster muscle in only 30% of the animals received its total blood supply through the superior external pudendal artery. In Wistar rats the same was true in less than 45%. The cremaster muscle of the rest of the animals appeared to receive its blood either in part or in total from the hypogastric trunk. We suggest that the name pudic-epigastric trunk be abandoned.

Terapia e evoluçäo do candidato a receptor do transplante cardíaco / Therapy and evolution of the candidate to heart transplantation

As doenças mais comuns que acometem o candidato a transplante cardíaco säo as cardiomiopatias, a doença coronária e, menos frequentemente, a doença cardíaca congênita e a rejeiçäo do enxerto. No Estudo de Framingham, foi demonstrado que a sobrevivência do paciente com insuficiência cardíaca é menor que 50 por cento em cinco anos após o início dos sintomas. Em outros estudos, na insuficiência cardíaca com sintomas avançados a sobrevivência chega a ser de 40 por cento - 60 por cento após um ano. O coecimento da fisiopatologia da insuficiência cardíaca, principalmente dos mecanismos neuro-hormonais e dos fatores prognósticos, tem proporcionado abordagens terapêuticas mais adequadas para melhorar os sintomas, a qualidade de vida e a sobrevivência dese grupo de pacientes. Apesar da melhora na sobrevida, o prognóstico ainda continua pobre; por isso, novas abordagens devem ser encontradas. A abordagem terapêutica de que dispomos no momento serve para retardar a evoluçäo da doença e controlar o paciente oo ponte para o transplante cardíaco.