Ophthalmic Complications of Bariatric Surgery

Obesity is increasing vastly in the world, and the number of bariatric surgeries being performed is also increasing. Patients being submitted to bariatric surgeries, especially malabsorptive procedures, have an increased risk of developing nutrient deficiencies, which can culminate in symptomatic hypovitaminosis, if supplementation is not done correctly. The eye and the optic system need an adequate level of several vitamins and minerals to perform properly, especially vitamin A, and this article wants to cover the main nutrients involved, the possible ophthalmic complications that can arise by their deficiency, and the management of those complications.

Onychomycosis in Patients with Chronic Leg Ulcer and Toenail Abnormalities

Nails have a limited number of reactive patterns to disease. Accordingly, toenail changes of different etiologies may mimic onychomycosis. OBJECTIVE To determine the prevalence of toenail onychomycosis among patients with leg ulcer and toenail abnormalities attending a dermatology clinic. METHODS A cross-sectional study was conducted through the analysis of clinical records and results of mycological examination. RESULTS A total of 81 patients were included, with a median age of 76.0 years. Most ulcers were of venous etiology, followed by those of mixed and arterial pathogenesis. The mycological evaluation confirmed the diagnosis of onychomycosis in 27.2% of the patients. The etiologic agent was a dermatophyte in 59.1% of isolates in nail samples, while Trichophyton interdigitale was the most frequent fungal species (40.9%). CONCLUSIONS Most toenail abnormalities in patients with chronic leg ulcer were not onychomycosis. This study highlights the importance of systematic mycological examination in these patients, in order to avoid overtreatment with systemic antifungals, unnecessary costs and side effects.

Patologia óssea do insuficiente renal crónico: desafio clínico-biológico ; Caracterização da osteodistrofia renal e efeitos da biocompatibilidade de membranas de hemodiálise, na remodelação óssea

Resumo: Os resultados das nossas investigações, apresentadas ao longo desta dissertação,contribuíram para a otimização do diagnóstico invasivo e não invasivo da osteodistrofia renal e permitiram evidenciar a relevância, para a expressão clínica e histológica da ODR, de algumas articularidades específicas da população hemodialisada, nomeadamente: a utilização de membranas de hemodiálise mais biocompatíveis e com elevada permeabilidade, o recurso a técnicas de hemodiafiltração com otimização da capacidade convectiva, as limitações dos marcadores bioquímicos de remodelação óssea ou a insuficiência / deficiência em vitamina D nativa (bem como os resultados da suplementação com esta vitamina). Testámos, pela primeira vez em doentes hemodialisados, novos marcadores da formação e reabsorção óssea, que validámos mediante a comparação com os resultados da histomorfometria óssea. No seu conjunto, e de forma integrada, as nossas investigações permitiram-nos: - Evidenciar a diminuição da expressão do recetor da PTH/PTHrP na cartilagem de crescimento, num modelo animal de IRC, o que explica, pelo menos em parte, o atraso de crescimento observado nesta patologia, bem como a diminuição da resposta à ação da PTH; - Demonstrar as vantagens da determinação da isoforma óssea da fosfatase alcalina, em relação à fosfatase alcalina total, no diagnóstico diferencial entre baixa e elevada remodelação óssea; - Utilizar, pela primeira vez em hemodialisados, a piridinolina e a desoxipiridinolina no diagnóstico da reabsorção óssea. Este foi o primeiro marcador sérico específico da atividade osteoclástica, utilizado com sucesso em doentes anúricos em hemodiálise. Evidenciámos uma excelente correlação destes dois marcadores bioquímicos com a superfície osteoclástica e com o número de osteoclastos/mm2;- Demonstrar as acentuadas limitações de outros marcadores da formação e reabsorção óssea (nomeadamente a osteocalcina, o propeptido carboxiterminal do procolagénio tipo I-PICP, e o Telopeptido do colagénio tipo I – ICTP) com base nas correlações entre os doseamentos séricos ou plasmáticos destes marcadores e a biópsia óssea com avaliação histomorfométrica; -Evidenciar as limitações induzidas pela sobrecarga alumínica na interpretação dos níveis séricos dos marcadores não invasivos da remodelação óssea;-Testar a eficácia e segurança da utilização de “microdoses” de desferroxamina na terapêutica da intoxicação alumínica, em doentes com acentuada exposição a este metal;-Demonstrar que os doentes hemodialisados cronicamente com dialisadores de poliacrilonitrilo (membranas de alta permeabilidade),apresentavam menor ativação osteoblástica e osteoclástica, que os doentes dialisados com membranas de cuprofano(baixa permeabilidade), sendo os níveis de iPTH semelhantes em ambos os grupos estudados. Estes resultados apontam para uma menor ativação da remodelação óssea quando se utilizam membranas de hemodiálise mais biocompatíveis e/ou de maior permeabilidade, o que se poderá relacionar com a ultrafiltração de mediadores da ativação celular ou com a menor ativação dos mecanismos estimuladores da remodelação óssea, por parte destas membranas. Entre os mediadores da remodelação óssea que demonstrámos serem relevantes e estarem aumentados no soro de hemodialisados com membranas de baixo fluxo, contam-se a beta-2-microglobulina (2-M) e algumas citoquinas, com ação estimuladora das linhagens celulares envolvidas na remodelação óssea. Demonstrámos igualmente uma correlação positiva dos níveis séricos de 2-M com os níveis séricos da osteocalcina, da isoenzima óssea da fosfatase alcalina (marcadores da formação óssea) e com os níveis séricos da piridinolina (marcador da reabsorção óssea). Os níveis séricos de 2-M correlacionaram-se ainda, de forma negativa, com o volume osteoide (matriz óssea não calcificada). Nestes doentes hemodialisados, demonstrámos a presença de níveis séricos aumentados da interleucina-1, do antagonista do recetor da interleucina-1, da interleucina-6 e do recetor solúvel da interleucina-6. Salientamos as relações inversas que observámos, por um lado entre os níveis de antagonista do recetor da interleucina-1 e a superfície osteoblástica, e por outro lado entre o rácio do recetor da interleucina-6 / interleucina-6 (IL6-r/IL6) e a superfície osteoclástica. De acordo com estes nossos resultados originais, entendemos que a interferência nos níveis circulantes e na ativação local destes mediadores poderá justificar, em grande parte, o aumento da prevalência de doença óssea adinâmica, descrita por nós e por outros grupos. Evidenciámos uma elevadíssima prevalência de doença adinâmica (>50% dos doentes), numa população de hemodialisados sem exposição prévia ao alumínio, tratados de acordo com os K/DOQI “guidelines” e que ao longo de um ano mantiveram níveis séricos de cálcio e de fósforo controlados. Consequentemente, os doentes tratados de forma otimizada apresentaram uma prevalência surpreendentemente elevada de doença adinâmica. Os nossos resultados (classificados com o grau de evidência máxima pelos peritos KDIGO) contribuíram para dar suporte à grande diferença nos guidelines K/DOQI (2003) e KDIGO (2009) no que respeita aos valores alvo da PTH. Estamos conscientes que de que o facto de termos uma percentagem tão elevada de doença óssea adinâmica nas nossas populações de hemodialisados, bem como a demonstração de que alguns doentes com valores de PTH intacta (2ª geração) de cerca de 600 pg/ml tinham doença óssea adinâmica, condicionaram os novos objetivos KDIGO para a PTH. Os nossos resultados suportam, em nossa opinião, a adequação e vantagem da utilização dos critérios da KDIGO em vez dos KDOQI. Tendo em conta que os primeiros definem objetivos para a PTH entre 2 e 9 vezes o limite superior do normal e não se comprometem com valores alvo absolutos e rígidos (definidos previamente nos KDOQI entre 150 e 300 pg/mL), esta nova abordagem parece-nos mais correta.Na nossa investigação clínica, caracterizámos ainda a população hemodialisada portuguesa no que respeita aos níveis séricos de calcidiol, identificando a população com suficiência, insuficiência ou deficiência em vitamina D3. Documentámos uma acentuada prevalência de insuficiência e mesmo de deficiência nesta vitamina, numa vasta população de hemodialisados, a qual, muito provavelmente, reflete de forma fidedigna, o que se pode observar na restante população de doentes portugueses IRC em estádio 5d (em diálise). Descrevemos, pela primeira vez em doentes hemodialisados, uma associação entre deficiência em calcidiol e a presença de fatores de risco cardiovascular (que têm sido identificados nos doentes urémicos). A nossa investigação conduziu-nos a resultados originais, ao identificar os níveis baixos de 25(OH)vitamina D3 como um provável fator de risco cardiovascular em hemodialisados, visto que a deficiência nesta vitamina se associou, de forma muito significativa, ao aumento da prevalência de calcificações vasculares, a inflamação, a pressão de pulso mais elevada, a hipertrofia ventricular esquerda, a insuficiência cardíaca e a níveis séricos aumentados de “BNP-Brain natriuretic peptide”. Finalmente, numa avaliação prospetiva, de intervenção terapêutica, corrigimos a insuficiência ou deficiência em 25(OH)vitamina D3 e demonstrámos que essa correção se associou a uma redução dos fatores de risco cardiovascular. Esta última intervenção foi totalmente inovadora, visto ser a primeira avaliação prospetiva da evolução dos fatores de risco cardiovasculares, em função da suplementação com vitamina D nativa, em doentes hemodialisados. Em resumo, pensamos que os resultados das nossas investigações, acima sumarizadas e apresentadas ao longo dos diversos capítulos desta dissertação,contribuiram para uma nova perspetiva da osteodistrofia renal e para recolocar o foco da atenção dos nefrologistas no tecido ósseo e no eixo paratormona – vitamina D – remodelação óssea. Este eixo surje claramente envolvido em múltiplos processos fisiopatológicos, que suportam a elevada morbilidade e mortalidade (nomeadamente de causa cardiovascular) observada nos doentes urémicos.---------ABSTRACT: The results of our research, presented throughout this thesis, contributed towards the optimisation of the invasive and non-invasive diagnosis of renal osteodystrophy. They have also highlighted the importance, to the clinical and histological expression of the ODR, of some specific characteristics of the haemodialysis population, including: the use of biocompatible high permeability haemodialysis membranes, the use of haemodiafiltration techniques with convection enhancement, as well as the limitations of biochemical markers of bone turnover or native vitamin D insufficiency/deficiency (along with the supplementation results of this vitamin). New bone formation and resorption markers, which were validated by comparison with the results of bone histomorphometry, have been tested for the first time on haemodialysis patients.As a whole, and in an integrated approach, our research enabled us to: - Show the decrease of the PTH/PTHrP receptor expression in cartilage growth, used on an IRC animal model, which explains, to some extent, not only the delayed growth observed in this pathology, but also the slow response to PTH. - Point out the advantages of the determination of bone isoform of alkaline phosphatase, in relation to the total alkaline phosphatase, in the differential diagnosis between low and high-bone turnover.- Use pyridinoline and deoxypyridinoline in the diagnosis of bone resorption for the first time on haemodialysis patients. This was the first specific serum market of the osteoclastic activity, which was successfully used on anuric patients undergoing haemodialysis treatment. We also observed an excellent correlation of these biochemical markers with the osteoclastic surface and the number of osteoclasts/mm2. - Demonstrate the sharp limitations of other markers of bone formation and resorption (namely osteocalcin, carboxyterminal propeptide of type I-PICP procollagen and telopeptide of type I-ICTP collagen) based on correlations between these markers’ serum or plasma assays and bone biopsy with histomorphometric assessment.-Show the limitations induced by aluminium overload in the interpretation of serum levels of bone remodelling non-invasive markers.-Test the efficacy and the safety of the use of deferoxamine “microdoses” for treatment of aluminium overload among patients with high levels of serum aluminium. - Demonstrate that patients with chronic haemodialysis dialysers of polyacrylonitrile (high permeability membranes) show a lower osteoblastic and osteoclastic activation than those undergoing dialysis with cuprofan membranes (low permeability), being the iPTH levels similar in both groups of patients. These findings point towards a lower activation of bone remodelling when using more biocompatible dialysis membranes and/or of higher permeability, which may relate to the ultrafiltration of cell activation mediators or to the lower activation of the stimulating mechanisms of bone remodelling, regarding the membranes. Beta-2-microglobulin (2-M) and some cytokines that play a role/participate in bone remodelling are among the bone remodelling mediators, which we demonstrated to be relevant and to be increased in the serum of haemodialysis with low flow membranes. We also proved that there is a positive correlation of serum 2-M levels not only with serum osteocalcin levels, of the bone isoenzyme of alkaline phosphatase (bone forming markers), but also with levels of serum pyridinoline (bone resorption marker).Serum 2-M levels correlate negatively with the volume of osteoid (uncalcified bone matrix). We also demonstrated the presence of elevated serum levels of interleukin-1,interleukin-1 receptor antagonist, interleukin-6 and soluble interleukin-6 receptor in haemodialysis patients. We stress the inverse relationship which we observed on one hand between the interleukin-1 receptor antagonist levels and the osteoblastic surface and on the other between the ratio of interleukin-6 receptor / interleukin-6 (IL6-r/IL6) and the osteoblastic surface. According to these unique findings, we believe that the interference in the circulating levels and in the local activation of these mediators may partly explain the rising prevalence of adynamic bone disease. A high prevalence of adynamic disease has also been observed in a haemodialysis population (>50% of patients) with no previous exposure to aluminium. The patients were treated according to K/DOQI guidelines and maintained controlled serum calcium and phosphorus levels over one year. As a result, the patients who received optimised treatment showed a surprisingly high prevalence of adynamic disease. Our results, which were ranked with the highest degree of evidence by KDIGO experts, contributed to the great difference regarding the target values of PTH in the K/DOQI (2003) and KDIGO (2009) guidelines. We are aware that the finding of such a high percentage of adynamic bone disease in our haemodialysis population, as well as the evidence that some patients with intact PTH values (2nd generation) of 600 pg/ml suffered from adynamic bone disease, have hindered, the new KDIGO objectives to PTH.In our opinion, our results support the suitability and the advantage of using KDIGO criteria instead of KDOQI. This seems to be the right approach when taking into consideration that KDIGO sets objectives to PTH between 2 and 9 times the normal upper limit and does not compromise with the rigid and absolute target values (between 150 and 300 pg/mL) previously defined by KDOQI. In our clinical research, the Portuguese haemodialysis population was characterised in terms of serum clacidiol levels and identified as having vitamin D3 sufficiency, insufficiency or deficiency. It was also recorded the prevalence of severe vitamin D3 insufficiency and even deficiency in a large haemodialysis population, which most likely provides a reliable picture of the rest of the population in IRC Portuguese patients with 5d stage (undergoing dialysis). We described for the first time in aemosialysis patients an association between calcidiol deficiency and the presence of ardiovascular risk factors, (which have been identified on uraemic patients).Our research led us to unique findings by having identified the low levels of 25(OH) vitamin D3 as a likely cardiovascular risk factor in patients undergoing haemodialysis treatment, given that deficiency in this vitamin has been significantly associated not only with a rise in the prevalence of vascular calcifications, but also inflammation, left ventricular hypertrophy, high pulse pressure and high serum BNPBrain natriuretic peptide levels. Finally, based on a prospective assessment of therapeutic intervention, 25(OH)vitamin D3 insufficiency or deficiency was corrected and we were able to demonstrate that this same correction was associated with a reduction in cardiovascular risk factors. This was a forward-looking intervention regarding the supplementation of native vitamin D in haemodialysis patients, since it was the first prospective assessment of the evolution of cardiovascular risk factors. In short, the results of our research, summarised above and presented throughout the various chapters of this thesis, contributed towards a new perspective of the renal osteodystrophy and also to draw the nephrologists’ attention to the bone tissue and to the axis PTH – vitamin D – bone remodelling. This axis appears clearly involved in multiple physiopathological processes, which support the high morbidity and mortality rate, (particularly of cardiovascular causes), observed in uraemic patients.

Hepatic Artery Thrombosis in Live Liver Donor Transplantation: How to Solve - a Case Report

The decrease in the number of cadaveric donors has proved a limiting factor in the number of liver transplants, leading to the death of many patients on the waiting list. The living donor liver transplantation is an option that allows, in selected cases, increase the number of donors. One of the most serious complications in liver transplantation is hepatic artery thrombosis, in the past considered potentially fatal without urgent re-transplantation. A white male patient, 48 years old, diagnosed with hepatocellular carcinoma in chronic liver failure caused by hepatitis B virus, underwent living donor liver transplantation (right lobe). Doppler echocardiography performed in the immediate postoperative period did not identify arterial flow in the right branch, having been confirmed thrombosis of the right hepatic artery in CT angiography. Urgent re-laparotomy was performed, which consisted of thrombectomy and re-anastomosis of the hepatic artery with segmental splenic artery allograft interposition. The patient started anticoagulation and antiplatelet therapy with acetylsalicylic acid. Serial evaluation with Doppler echocardiography showed hepatic artery patency. At present, the patient is asymptomatic. One of the most devastating complications in liver transplantation, and particularly in living liver donor, is thrombosis of the hepatic artery; thus, early diagnosis and treatment is vital. The rapid intervention for revascularization of the graft avoids irreversible ischemia of the bile ducts and hepatic parenchyma, thus avoiding the need for re-transplantation.

The Proarrhythmic Effect of Cardiac Resynchronization Therapy: an Issue that Should Be Borne in Mind

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system.

Multiple Mechanical Complications in ST-Segment Elevation Myocardial Infarction with Angiographically Normal Coronary Arteries

This case report discusses an unusual presentation of ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries and severe mechanical complications successfully treated with surgery. An 82-year-old man presented STEMI with angiographically normal coronary arteries and no major echocardiographic alterations at discharge. At the first month follow-up, he complained of fatigue and dyspnea, and contrast echocardiography complemented by cardiac magnetic resonance imaging revealed a large left ventricular apical aneurysm with a thrombus communicating by two jets of a turbulent flow to an aneurysmatic formation of the right ventricular apex. The patient underwent a Dor procedure, which was successful. Ventricular septal defects and ventricular aneurysms are rare but devastating complications of STEMI, with almost all patients presenting multivessel coronary artery disease. Interestingly in this case, the angiographic pattern was normal.

Effect of C282Y Genotype on Self-Reported Musculoskeletal Complications in Hereditary Hemochromatosis

OBJECTIVE: Arthropathy that mimics osteoarthritis (OA) and osteoporosis (OP) is considered a complication of hereditary hemochromatosis (HH). We have limited data comparing OA and OP prevalence among HH patients with different hemochromatosis type 1 (HFE) genotypes. We investigated the prevalence of OA and OP in patients with HH by C282Y homozygosity and compound heterozygosity (C282Y/H63D) genotype. METHODS: A total of 306 patients with HH completed a questionnaire. Clinical and demographic characteristics and presence of OA, OP and related complications were compared by genotype, adjusting for age, sex, body mass index (BMI), current smoking and menopausal status. RESULTS: In total, 266 of the 306 patients (87%) were homozygous for C282Y, and 40 (13%) were compound heterozygous. The 2 groups did not differ by median age [60 (interquartile range [IQR] 53 to 68) vs. 61 (55 to 67) years, P=0.8], sex (female: 48.8% vs. 37.5%, P=0.18) or current smoking habits (12.4% vs. 10%, P=0.3). As compared with compound heterozygous patients, C282Y homozygous patients had higher median serum ferritin concentration at diagnosis [1090 (IQR 610 to 2210) vs. 603 (362 to 950) µg/L, P<0.001], higher median transferrin saturation [80% (IQR 66 to 91%) vs. 63% (55 to 72%), P<0.001]) and lower median BMI [24.8 (22.1 to 26.9) vs. 26.2 (23.5 to 30.3) kg/m2, P<0.003]. The overall prevalence of self-reported OA was significantly higher with C282Y homozygosity than compound heterozygosity (53.4% vs. 32.5%; adjusted odds ratio [aOR] 2.4 [95% confidence interval 1.2-5.0]), as was self-reported OP (25.6% vs. 7.5%; aOR 3.5 [1.1-12.1]). CONCLUSION: Patients with C282Y homozygosity may be at increased risk of musculoskeletal complications of HH.

First Diabetic Retinopathy Prevalence Study in Portugal: RETINODIAB Study-Evaluation of the Screening Programme for Lisbon and Tagus Valley Region

BACKGROUND/AIMS: In Portugal, so far, there is no study or even accurate data on the prevalence of diabetic retinopathy (DR), based on a large representative sample and on a long-term follow-up. The objective of our study was to determine the prevalence of DR based on a national screening community-based programme. METHODS: A 5-year retrospective analysis of the RETINODIAB screening programme results was implemented in Lisbon and Tagus Valley area between July 2009 and October 2014. We estimated the prevalence of retinopathy for all patients with type 2 diabetes and studied the association between known risk factors and retinopathy emergence at their first screening. RESULTS: Throughout this period, from a total of 103 102 DR readable screening examinations, 52 739 corresponded to patients who attended RETINODIAB screening at entry. Globally, DR was detected in 8584 patients (16.3%). Of these, 5484 patients (10.4%) had mild non-proliferative (NP) DR, 1457 patients (2.8%) had moderate NPDR and 672 (1.3%) had severe NPDR. Finally, 971 patients (1.8%) had proliferative DR requiring urgent referral to an ophthalmologist. The presence of any DR, non-referable DR or referable DR was strongly associated with increasing duration of diabetes and earlier age at diagnosis. CONCLUSIONS: The prevalence rate of DR in our study (16.3%) was slightly lower than other published international data. The RETINODIAB network proved to be an effective screening programme as it improved DR screening in Lisbon and Tagus Valley surrounding area

Pulmonar Vascular Changes in the Plain Chest Film of Cardiac Patients

The correct interpretation of chest film on cardiac patients is very important. The most important feature is the radiographic appearance of the pulmonary vascularity. Four different patterns of pulmonary vascularity are considered: normal, decreased, increased and uneven. The different diseases associated with each type are mentioned. From the pulmonary vascular pattern one can deduct hemodynamic data which are important for the diagnosis, grade of severity and follow-up.

The Use of Statins in People at Risk of Developing Diabetes Mellitus: Evidence and Guidance for Clinical Practice

Reducing low-density lipoprotein cholesterol (LDL-C) levels using statins is associated with significant reductions in cardiovascular (CV) events in a wide range of patient populations. Although statins are generally considered to be safe, recent studies suggest they are associated with an increased risk of developing Type 2 diabetes (T2D). This led the US Food and Drug Administration (FDA) to change their labelling requirements for statins to include a warning about the possibility of increased blood sugar and HbA1c levels and the European Medicines Agency (EMA) to issue guidance on a small increased risk of T2D with the statin class. This review examines the evidence leading to these claims and provides practical guidance for primary care physicians on the use of statins in people with or at risk of developing T2D. Overall, evidence suggests that the benefits of statins for the reduction of CV risk far outweigh the risk of developing T2D, especially in individuals with higher CV risk. To reduce the risk of developing T2D, physicians should assess all patients for T2D risk prior to starting statin therapy, educate patients about their risks, and encourage risk-reduction through lifestyle changes. Whether some statins are more diabetogenic than others requires further study. Statin-treated patients at high risk of developing T2D should regularly be monitored for changes in blood glucose or HbA1c levels, and the risk of conversion from pre-diabetes to T2D should be reduced by intensifying lifestyle changes. Should a patient develop T2D during statin treatment, physicians should continue with statin therapy and manage T2D in accordance with relevant national guidelines.