Spontaneous Intracranial Hypotension and Multi-Level Cervical and Lumbar Epidural Blood Patches: A Case Report.

Spontaneous intracranial hypotension (SIH) is a neurologic condition where the intracranial pressure is reduced due to a loss of cerebrospinal fluid from its reservoir, the intrathecal space, to surrounding tissues. It is commonly characterized by an incapacitating headache, phono-photophobia, nausea, and vomiting, commonly refractory to medical treatment and requires further investigation. We describe the case of a healthy young man who presented to the emergency room with a postural headache, accompanied by nausea, vomiting, and phono-photophobia. Brain computed tomography (CT) imaging study was unremarkable and he was initially treated symptomatically. Because of persisting pain even on medical treatment, additional imaging studies, including a myelo-CT scan, were performed and a diagnosis of multi-level cerebrospinal fluid fistulas was made. To treat the underlying cause, a first epidural blood patch (EBP) was initially performed at C7-T1 with 20 mL of autologous blood, but failed to provide complete symptomatic relief. Months later, a second EBP was conducted at C6-C7 with higher volume (30 mL) but as in the first EBP this procedure too did not result in total resolution of the headache and accompanying symptoms. Since there was no surgical indication from Orthopedics and Neurosurgery and the symptoms persisted, a third EBP was carried out, this time at a lumbar level (L2-L3) with infusion of 60 mL of blood so the upper dorsal and cervical epidural space was reached. This resulted in a better symptom relief, allowing the patient to now carry out his normal activities with only residual pain. The need for repeat procedures is one of the pitfalls of the blood patching technique. If possible, it should be performed at the level of the documented fistula, but always with safety in mind and by experienced hands, especially when cervical levels are concerned. A consensus has not been reached regarding the blood volume to be administered; however, any discomfort or pain reported by the patient should be seen as warning sign and the procedure should be interrupted. Although not being a perfect solution, EBP can completely or partially resolve SIH symptoms, without the need for surgical intervention.

Growth hormone directly favors hepatic ketogenesis in persons with prediabetes or type 2 diabetes mellitus treated with empagliflozin.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabetic patients under empagliflozin treatment. METHODS: Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased ß-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma ß-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.

Portuguese Consensus and Recommendations for Acquired Coagulopathic Bleeding Management (CCBM).

We aimed to determine how Portuguese physicians handle major bleeding. We also aim to establish global diagnostic and therapeutic recommendations to be followed in clinical practice by using a step-wise approach of evidence generation. This study followed a three-step process: a steering committee desk review, a Delphi technique, an expert panel meeting. A modified 3-round Delphi including 31 statements was performed. Questions were answered in a five-point Likert-type scale. Consensus threshold was established as a percentage of agreement among participants ≥90% in the first round, and ≥85% in the second and third rounds. The level of consensus achieved by panelists was discussed with the scientific committee (January-2020). Fifty-one physicians participated in the study (compliance rate >90%). Analyzing the three rounds, consensus was reached on 20 items (64.5%) in the first, 4/11 items (36.4%) in the second and 6/7 items (85.7%) in the third. One statement about administration of clotting factor concentrates for bleeding control did not reach consensus. A high level of consensus was reached toward the need for implementing Patient Blood Management strategies in Portuguese hospitals, reduce exposure to allogeneic blood components, to use goal directed therapies for acquired bleeding management, and the need for evaluating blood transfusion indirect costs. A final version with 12 recommendations was built, according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Our results provide critically appraised and updated evidence on bleeding coagulopathies management in Portugal. Additional studies, mainly about indirect costs of blood transfusion, are needed.

Interventional Algorithm in Gastrointestinal Bleeding-An Expert Consensus Multimodal Approach Based on a Multidisciplinary Team.

The approach to the patient with gastrointestinal bleeding (GIB) can be very complex. A multidisciplinary panel of physicians with expertise in Gastroenterology, Anesthesiology, and Transfusion Medicine worked together to provide the best knowledge and guide clinical practitioners in the real setting of health institutions, characterized by disparate availability of human and technical resources. The authors propose a global and personalized approach according to different clinical scenarios to improve the outcomes of patients with GIB, for whom the reduction of inappropriate transfusions is crucial. The goal of this document is to provide clear and objective guidance through interventional algorithms toward a goal-directed approach according to the clinical situation and supported by the latest available scientific data on GIB management in different settings.

Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells.

BACKGROUND: Silver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag1+) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag1+ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag1+ concentrations found in these patients, we evaluated the Ag1+ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro. METHODS: Twenty patients with an average burned body surface area of 27.68% were included in this study. RESULTS: Patients' Ag1+ serum levels reached up to 558 times those of the unexposed controls. Ag1+ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1ß, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM). CONCLUSION: These findings suggest that Ag1+ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.

Quality of Sleep among Portuguese Anaesthesiologists: A Cross-Sectional Study.

INTRODUCTION: Sleeping is essential to maintain proper relationships with others, keep alertness, and execute responsibilities, among many other functions. In the medical profession, there are several studies linking sleep deprivation with a decrease in responsiveness, cognition and attention. With this study we intended to characterize the sleep pattern of Portuguese anaesthesiologists and identify independent factors associated with sleep quality in this population. MATERIAL AND METHODS: An observational, cross-sectional study of senior and resident anesthesiologists working in Portugal was carried out through an online questionnaire. Individuals working exclusively in intensive care units, emergency departments or with previously diagnosed sleep disorders were excluded. Socio-demographic data, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and Perceived Stress Scale were applied. Statistical significance was assessed using the Mann-Whitney test and the chi-square test. A multivariable analysis was performed to examine the association between the Pittsburgh Sleep Quality Index and certain variables. RESULTS: Among 256 respondents, 46.1% reported "poor" quality of sleep (Pittsburgh Sleep Quality Index > 5). Within these individuals, 77.1% slept less than 7 hours per night (p < 0.001). Excessive daytime sleepiness (Epworth Sleepiness Scale > 10) was present in 41.0% of the sample, and the median Perceived Stress Scale score was 17.0. The independent factors associated with worse quality ofsleep were the number of working hours/week (OR 1.03, 95% CI 1,01 to 1,06), perceived stress (OR 1.18, 95% CI 1.11 to 1.26), taking sleep medication (OR 14.72, 95% CI 5.55 to 39.08), and sleep hours/night (OR 0.25, 95% CI 0.15 to 0.42). DISCUSSION: This fraction of Portuguese anaesthesiologists presented a poorer quality of sleep, with excessive daytime somnolence, perceived stress and higher sedative use compared to previously studied populations. CONCLUSION: Our study characterizes sleep patterns and identifies potential risk factors linked to sleep disturbances in a sample of Portuguese anaesthesiologists. Government and institutional policies can endorse sleep hygiene practices and habits, promoting healthier working environments.

Introdução: O sono é essencial para executar tarefas, manter o estado de alerta, executar tarefas, entre outras funções. Diversos estudos na área médica relacionam a privação de sono com a redução da capacidade de resposta, cognição e nível de atenção. Os objetivos deste estudo foram a caracterização do padrão de sono dos anestesiologistas Portugueses e identificação de fatores de risco independentes para pior qualidade de sono. Material e Métodos: Efetuámos um estudo observacional e transversal em anestesiologistas e internos de formação específica em Anestesiologia a trabalhar em Portugal. Foram excluídos profissionais que trabalham exclusivamente em unidades de cuidados intensivos, serviços de urgência ou com patologias do sono previamente diagnosticadas. Foram colhidos dados sócio-demográficos e aplicadas as escalas de Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) e Perceived Stress Scale (PSS). A significância estatística foi analisada recorrendo aos testes de Mann-Whitney e qui-quadrado. A associação entre o Pittsburgh Sleep Quality Index e demais variáveis foi testada através de uma regressão logística. Resultados: Dos 256 casos admitidos, 46,1% apresentaram "má" qualidade de sono (Pittsburgh Sleep Quality Index > 5). Nestes, 77,1% dormiram menos de 7 horas por noite (p < 0,001). A sonolência diurna excessiva (Epworth Sleepiness Scale > 10) surgiu em 41,0% da amostra e a mediana da Perceived Stress Scale foi 17,0. Os fatores de risco independentes para "má" qualidade de sono foram: número de horas de trabalho semanais (OR 1,03, IC 95% 1,01 a 1,06), stress percecionado (OR 1,18, IC 95% 1,11 a 1,26), toma de medicamentos para dormir (OR 14,72, IC 95% 5,55 a 39,08) e número de horas dormidas por noite (OR 0,25, IC 95% 0,15 a 0,42). Discussão: A nossa amostra de anestesiologistas Portugueses apresentou pior qualidade de sono, com sonolência diurna excessiva, stress percecionado e uso de sedativos superiores a outras populações previamente estudadas. Conclusão: O presente estudo caracteriza o padrão de sono e identifica potenciais factores de risco relacionados com distúrbios do sono, numa amostra de Anestesiologistas Portugueses. Políticas de saúde governamentais e institucionais poderão ser orientadas para a promoção da higiene do sono, levando a ambientes de trabalho mais saudáveis.

Physical Function, Quality of Life, and Energy Expenditure During Activities of Daily Living in Obese, Post-Bariatric Surgery, and Healthy Subjects.

OBJECTIVES: This study aimed to evaluate physical function (PF), quality of life (QOL), and energy expenditure (EE) during activities of daily living (ADL) in late outcome post-bariatric surgery (BS) patients and to compare them to severe obese individuals and matched controls. METHODS: Sixty-three subjects were included: 21 patients in post-operative (PO) of BS (3-4 years post-Roux-en-Y gastric bypass) with a stable weight for at least 6 months (16 women, 41 ± 11 years old, BMI = 28 ± 4 kg m-2) (group PO); 21 obese individuals with BS indication (16 women, 44 ± 9 years old, BMI = 44 ± 6 kg m-2) (group OB); and 21 controls matched to PO by gender, age, and BMI (16 women, 42 ± 12 years old, BMI = 27 ± 6 kg m-2) (group MC). PF was objectively assessed by the Glittre and modified Glittre ADL-tests. QOL (SF-36), EE (activity monitoring during ADL), and body composition (bioelectrical impedance) were also assessed. RESULTS: OB had worse PF (Glittre ADL-test) compared to PO and MC (OB = 224 ± 76 s; PO = 143 ± 39 s; and MC = 118 ± 17 s; p < 0.0001). The same was observed for QOL (p < 0.05 for all SF-36 domains). OB also had higher total EE in the Glittre ADL-test. However, 63% of the activity time was in low-intensity EE. In the Glittre modified protocol, OB had poorer performance than PO and MC when walking up/downstairs, rising/sitting in a chair, and moving objects on a shelf. CONCLUSIONS: Post-BS patients have better PF and QOL and perform activities under lower total EE than obese subjects, very similar to matched controls.

Validity and Reproducibility of the Glittre ADL-Test in Obese and Post-Bariatric Surgery Patients.

BACKGROUND: Obese and post-bariatric surgery (BS) subjects often present limitations in physical functioning (PF). The Glittre ADL-test is a simple and useful way to evaluate this outcome. It includes functional activities such as rising from a chair, lifting, carrying weights, and bending over and was never studied in the obese population. This study aimed to determine the validity and reproducibility of the Glittre ADL-test to evaluate PF in obese, post-BS, and healthy control subjects. METHODS: Twenty-one post-BS patients (3-4 years post-surgery) (16 women, 41 ± 11 years, BMI = 28 ± 4 kg m-2) (group PO); 21 obese individuals (16 women, 44 ± 9 years, BMI = 44 ± 6 kg.m-2) (group OB) and 21 control individuals matched to PO (16 women, 42 ± 12 years old, BMI = 27 ± 6 kg m-2) (group MC) were included. For the reproducibility analysis, the Glittre ADL-test was performed twice, with a 30-min interval. As criterion methods for the validation, subjects performed two walking tests and answered a health status questionnaire (SF-36). RESULTS: High intraclass correlation (OB: r = 0.91 and PO: r = 0.89; MC: r = 0.86; P < 0.0001 for all) and good Bland-Altman agreement between the two tests were found in all groups. However, learning effect ranged between 8.8 and 11.8 % and significant test-retest differences occurred. The test was valid for all groups (moderate-to-high significant correlations with the criterion methods). CONCLUSIONS: Glittre ADL-test is valid and reproducible to evaluate PF of obese, post-BS, and healthy control subjects. However, due to the large learning effect, two tests are required for accurate assessment.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy.

Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

A boy with Prader-Willi syndrome: unmasking precocious puberty during growth hormone replacement therapy

SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

Clinical, hormonal, ovarian, and genetic aspects of 46,XX patients with congenital adrenal hyperplasia due to CYP17A1 defects.

OBJECTIVE: To perform a clinical, biochemical, and molecular evaluation of patients with CYP17A1 defects, including ovarian imaging. DESIGN: Retrospective study. SETTING: Tertiary care center. PATIENT(S): Sixteen patients with congenital adrenal hyperplasia due to CYP17A1 defects with a median chronological age of 20 years and belonging to 10 unrelated families. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical and biochemical parameters, molecular diagnosis, ovarian imaging, and therapeutic management. RESULT(S): Seventy-one percent of patients presented with primary amenorrhea, 50% had no breast development, and pubic hair was absent or sparse in all patients; 88% had high blood pressure at diagnosis. Basal LH and P levels were high, and androgen levels were low in all patients. Ultrasound revealed ovarian enlargement in 68.7% and ovarian macrocysts in 62.5% of patients before treatment; three patients had a previous surgical correction of ovarian torsion or rupture. Molecular analysis revealed inactivating CYP17A1 mutations in all patients. The most prevalent mutation was p.W406R, and one patient bore a novel p.G478S/p.I223Nfs*10 compound heterozygous mutation. Treatment with dexamethasone, estrogen, and P resulted in reduction of ovarian volume. CONCLUSION(S): Amenorrhea, absent/sparse pubic hair, hypertension, and ovarian macrocysts, whichincrease the risk of ovarian torsion, are important elements in the diagnosis of 46,XX patients with CYP17A1 defects. High basal P levels in patients with hypergonadotropic hypogonadism point to the diagnosis of CYP17A1 defects. Fertility can be achieved in these patients with novel reproductive techniques.

Interventional Algorithms for the Control of Coagulopathic Bleeding in Surgical, Trauma, and Postpartum Settings: Recommendations From the Share Network Group.

Several clinical settings are associated with specific coagulopathies that predispose to uncontrolled bleeding. With the growing concern about the need for optimizing transfusion practices and improving treatment of the bleeding patient, a group of 9 Portuguese specialists (Share Network Group) was created to discuss and develop algorithms for the clinical evaluation and control of coagulopathic bleeding in the following perioperative clinical settings: surgery, trauma, and postpartum hemorrhage. The 3 algorithms developed by the group were presented at the VIII National Congress of the Associação Portuguesa de Imuno-hemoterapia in October 2013. They aim to provide a structured approach for clinicians to rapidly diagnose the status of coagulopathy in order to achieve an earlier and more effective bleeding control, reduce transfusion requirements, and improve patient outcomes. The group highlights the importance of communication between different specialties involved in the care of bleeding patients in order to achieve better results.

Adrenocorticotropic hormone but not high-density lipoprotein cholesterol or salivary cortisol was a predictor of adrenal insufficiency in patients with septic shock.

Relative adrenal insufficiency in sepsis has been extensively debated on; however, accurate diagnosis and therapeutic intervention remain controversial. The authors aimed to evaluate adrenocorticotropic hormone (ACTH), salivary cortisol, total cortisol and estimated plasma-free cortisol, cholesterol, and lipoproteins as predictors of adrenal insufficiency in patients within 24 h of septic shock diagnosis. This prospective study evaluated all hospitalized patients older than 18 years who developed septic shock and were using vasoactive drugs within 24 h of diagnosis. Blood and saliva samples were drawn at baseline and 60 min (T60) after 250 µg tetracosactide intravenous injection. Patients were divided into two groups: responders (Δ [T60 minus baseline] total cortisol >9 µg/dL) and nonresponders (Δ total cortisol ≤ 9 µg/dL or baseline total cortisol <10 µg/dL). The latter group was considered to have adrenal insufficiency. A total of 7,324 hospitalized patients were monitored, and 34 subjects with septic shock were included in the analysis. Adrenal insufficiency was found in 32.4%. Total cholesterol, high-density lipoprotein cholesterol, triglycerides, and salivary cortisol did not differ between groups. Estimated plasma-free cortisol was not better than total plasma cortisol in estimating adrenal function. Baseline endogenous ACTH was higher in nonresponders than responders (55.5 pg/mL vs. 18.3 pg/mL, respectively; P = 0.01). The cutoff ACTH value that discriminated patients with adrenal insufficiency was 31.5 pg/mL. Thus, endogenous ACTH measured within 24 h of septic shock diagnosis could predict adrenal response to tetracosactide.

Impaired antioxidant action of high density lipoprotein in patients with type 1 diabetes with normoalbuminuria and microalbuminuria.

AIMS: Patients with type 1 diabetes, in the absence of chronic complications, have serum concentrations of high density lipoprotein cholesterol (HDL-C) similar to the general population. However, their HDL particles may be dysfunctional. We aimed to evaluate the antioxidant effect of HDL2 and HDL3 obtained from Caucasian males with type 1 diabetes with normoalbuminuria and microalbuminuria. METHODS: Twenty Caucasian men with type 1 diabetes (10 with normoalbuminuria and 10 with microalbuminuria) and 10 healthy Caucasian men participated in the study. Lipoproteins were obtained by density gradient ultracentrifugation. The antioxidant effect of HDL was assessed by measuring lipid hydroperoxide (LOOH) concentration after 3h of pooled LDL oxidation catalyzed by 5µM CuSO4 in the absence or presence of HDL2 or HDL3. RESULTS: The control, normoalbuminuria, and microalbuminuria groups had similar HDL-C concentration and estimated glomerular filtration rate. Glycemic control was similar between diabetes groups (HbA1c 8.1±0.9% and 8.3±0.7%, P=0.70), but estimated glucose disposal rate was lower in patients with microalbuminuria (8.0±0.6 and 4.5±1.1mg/kg/min, P<0.01). The relative antioxidant effect of HDL2 from control, normoalbuminuria, and microalbuminuria groups were 92.8±2.4%, 85.4±1.7%, and 74.2±4.6%, respectively (P<0.01), and the HDL3 effect were 95.0±2.2%, 86.4±4.4%, and 75.3±4.2%, respectively (P<0.01). CONCLUSION: Both HDL2 and HDL3 inhibited LOOH formation in copper-catalyzed oxidation of LDL in vitro. Overall, this antioxidant effect was lower in Caucasian men with type 1 diabetes, and was further compounded in those with microalbuminuria.

Lipoproteins and CETP levels as risk factors for severe sepsis in hospitalized patients.

BACKGROUND: The magnitude of lipoprotein level reduction during the acute-phase response may be associated with the severity and mortality of sepsis. However, it remains to be determined whether low lipoprotein levels can be considered a risk factor for developing sepsis. We aimed to investigate lipoprotein levels as risk factors for sepsis in hospitalized patients, and also describe sequential changes in lipoprotein and cholesterol ester transfer protein (CETP) levels during sepsis. DESIGN: This is a prospective cohort study and case-control analysis from selected hospitalized patients. Blood samples were collected at admission, and participants were monitored for severe sepsis. Total cholesterol, high density lipoprotein (HDL), low density lipoprotein, and triglyceride levels were compared between sepsis cases and controls. Cholesterol, apolipoprotein, phospholipid and CETP concentrations were monitored in the case group. RESULTS: Of 1719 enrolled patients, 51 developed severe sepsis and were paired with 71 controls by age, gender, presence of infection at admission and chronic disease. HDL cholesterol level at admission was a risk factor for severe sepsis (OR = 0.969; 95% CI: 0.944-0.995). Mean CETP levels diminished between hospital admission and day 3 of sepsis. The magnitude of this variation (Delta CETP) was more pronounced in non-survivors (0.78 +/- 1.08 microg mL(-1)) than that in survivors (0.02 +/- 0.58 microg mL(-1), P = 0.01). CONCLUSIONS: HDL cholesterol may have a protective effect against sepsis. Each 1 mg dL(-1) increase in HDL decreased the odds of severe sepsis by 3% during hospitalization. The reduction of plasma CETP was associated with mortality.

Prevalence of metabolic syndrome and associated risk factors in Brazilian schoolchildren.

OBJECTIVE: To determine the prevalence of metabolic syndrome (MetS) in schoolchildren from 6 to 16 years old, while considering their socio-economic status and other potential risk factors. DESIGN: A cross-sectional study was conducted between April and November of 2005 in a semi-rural city with a total population of 13,000 inhabitants. SETTING: The study was conducted in Maracai city, located in the Brazilian state of Sao Paulo. SUBJECTS: Schoolchildren (n 2170) of both genders, corresponding to approximately 82% of all Maracai schoolchildren, were evaluated for components of MetS, as defined by the National Cholesterol Education Program; reference values for children and adolescents were adjusted for age and sex. RESULTS: Overall, MetS prevalence was 3.6% (95% CI 2.9, 4.5) and did not differ statistically between genders, skin colour, between children and adolescents. However, when we analysed groups of subjects by weight, MetS prevalence progressively increased from 0.3% (95% CI 0.1, 0.8) in normal-weight subjects to 10.7% (95% CI 7.4, 14.8) and 34.5% (95% CI 25.9, 43.9) in overweight and obese subjects, respectively (both P < 0.001 compared to normal-weight controls). When socio-economic classes were considered, 4.7% high-income students (95% CI 3.5, 6.2) had MetS, which was significantly greater than low-income students (2.7%; 95% CI 1.9, 3.9; P = 0.023). CONCLUSIONS: MetS prevalence was high in overweight and obese schoolchildren and these risk factors were present during childhood and adolescence. Changes in lifestyle and alimentary safety should be encouraged to avoid future cardiovascular morbidity and type 2 diabetes mellitus.

Metformin increases HDL3-cholesterol and decreases subcutaneous truncal fat in nondiabetic patients with HIV-associated lipodystrophy.

The purpose of this study was to assess metformin effects on high-density lipoprotein (HDL) composition of patients with HIV-associated lipodystrophy (LDHIV). Twenty-four adult outpatients were enrolled to receive metformin (1700 mg/d) during 6 months, but 2 were lost to follow-up and 6 stopped the drug due to adverse events (gastrointestinal in 5, and excessive weight loss in 1). From the 16 subjects who completed the study, 69% were female. At baseline, 3 and 6 months, we assessed: weight, waist and hip circumferences, blood pressure, fasting glucose and insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), lipids, and HDL subfractions by microultracentrifugation. At 0 and 6 months, body fat distribution was assessed by computed tomography (CT) scan (L4 and middle femur). Metformin use was associated with reduction of mean weight (-2.4Kg at 6 months; p < 0.001), body mass index, waist, waist-to-hip ratio and a marked decrease in blood pressure (p < 0.001). Subcutaneous (p = 0.01) and total abdominal fat (p = 0.002) were reduced, but no change was found in visceral or thigh fat. No difference was detected on plasma glucose, insulin, HOMA2-IR, cholesterol or triglycerides, except for an increase in HDL3-cholesterol (from 21 mg/dL to 24 mg/dL, p = 0.002) and a reduction of nascent HDL (the fraction of plasma HDL-cholesterol not associated to subfractions HDL2 or HDL3) (p = 0.008). Adverse effects were very common, but most were gastrointestinal and mild. Thus, metformin use in LDHIV increases HDL3-cholesterol (probably due to improved maturation of HDL) and decreases blood pressure, weight, waist, and subcutaneous truncal fat, making this an attractive option for preventing cardiovascular disease in this population.

[Prevalence of HIV-associated lipodystrophy in Brazilian outpatients: relation with metabolic syndrome and cardiovascular risk factors]. / Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular.

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50% of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55% prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p<0.001) were independently associated with LDHIV. Concerning MS diagnostic criteria, high blood pressure was found in 32%, low HDL-cholesterol in 68%, hypertriglyceridemia in 55%, altered waist circumference in 17% and altered glycemia and/or diabetes in 23% of individuals. Abnormal waist and hypertriglyceridemia were more common in LDHIV-affected individuals. MS was diagnosed in 36%. In multivariate analysis, the factors associated with MS were: BMI >25 kg/m(2) (p<0.001), family history of obesity (p=0.01), indinavir (p=0.001) and age >40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65% versus 50%, p=0.051). LDHIV prevalence among our patients (55%) was similar to previous reports from other countries. MS prevalence in these HIV-infected individuals seems to be similar to the prevalence reported on Brazilian non-HIV-infected adults.

Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular / Prevalence of HIV-associated lipodystrophy in Brazilian outpatients: relation with metabolic syndrome and cardiovascular risk factors

A lipodistrofia associada ao HIV (LAHIV) acomete 40 por cento a 50 por cento dos pacientes infectados pelo vírus, mas sua prevalência no Brasil é desconhecida. O objetivo deste trabalho foi avaliar a prevalência de LAHIV entre adultos brasileiros infectados, bem como sua relação com fatores de risco cardiovascular e síndrome metabólica (SM). Foram avaliados 180 pacientes maiores de 18 anos, infectados por HIV, atendidos no Ambulatório de Infectologia da Universidade Estadual de Londrina. Por meio de entrevista e revisão de prontuário, foram avaliados dados antropométricos, pressão arterial, antecedentes mórbidos pessoais e familiares, duração da infecção por HIV e da aids, drogas anti-retrovirais utilizadas, CD4+, carga viral, glicemia e perfil lipídico. A LAHIV foi definida como a presença de alterações corporais percebidas pelo próprio paciente e confirmadas ao exame clínico. A SM foi diagnosticada usando os critérios do Adult Treatment Panel III (NCEP-ATPIII), revistos e atualizados pela American Heart Association (AHA/NHLBI). A prevalência observada de LAHIV foi de 55 por cento. Os pacientes com LAHIV apresentaram maior duração da infecção por HIV, da aids e do uso de anti-retrovirais. Na análise multivariada, estiveram independentemente associados ao risco de LAHIV: sexo feminino (p = 0,006) e duração da aids > 8 anos (p < 0,001). Quanto aos critérios para SM, hipertensão foi detectada em 32 por cento, baixo HDL-colesterol em 68 por cento, hipertrigliceridemia em 55 por cento, cintura aumentada em 17 por cento e glicemia aumentada e/ou diabetes em 23 por cento dos indivíduos. A cintura aumentada e a hipertrigliceridemia foram mais comuns em portadores de LAHIV. A SM foi identificada em 36 por cento dos pacientes. Na análise multivariada, estiveram associados à SM: IMC > 25 kg/m² (p < 0,001), história familiar de obesidade (p = 0,01), uso de indinavir (p = 0,001) e idade > 40 anos no diagnóstico do HIV (p = 0,002). A LAHIV apresentou...

Lipodystrophy in HIV-infected patients (LDHIV) affects 40-50 percent of HIV-infected patients, but there are no data on its prevalence in Brazil. The aim of this study was to assess the LDHIV prevalence among HIV-infected adult Brazilian individuals, as well as to evaluate LDHIV association with cardiovascular risk factors and the metabolic syndrome (MS). It was included 180 adult HIV-infected outpatients consecutively seen in the Infectology Clinic of Universidade Estadual de Londrina. Anthropometric and clinical data (blood pressure, family and personal comorbidities, duration of HIV infection/AIDS, antiretroviral drugs used, CD4+ cells, viral load, fasting glycemia and plasma lipids) were obtained both from a clinical interview as well as from medical charts. LDHIV was defined as the presence of body changes self-reported by the patients and confirmed by clinical exam. MS was defined using the NCEP-ATPIII criteria, reviewed and modified by AHA/NHLBI. A 55 percent prevalence of LDHIV was found. Individuals with LDHIV presented a longer infected period since HIV infection, longer AIDS duration and longer use of antiretroviral drugs. In multivariate analysis, women (p=0.006) and AIDS duration >8 years (p<0.001) were independently associated with LDHIV. Concerning MS diagnostic criteria, high blood pressure was found in 32 percent, low HDL-cholesterol in 68 percent, hypertriglyceridemia in 55 percent, altered waist circumference in 17 percent and altered glycemia and/or diabetes in 23 percent of individuals. Abnormal waist and hypertriglyceridemia were more common in LDHIV-affected individuals. MS was diagnosed in 36 percent. In multivariate analysis, the factors associated with MS were: BMI >25Kg/m² (p<0.001), family history of obesity (p=0.01), indinavir (p=0.001) and age >40 years on HIV first detection (p=0.002). There was a trend to higher frequency of LDHIV among patients with MS (65 percent versus 50 percent, p=0.051). LDHIV prevalence...