Centro Hospitalar de São João

Introduction: Cerebral venous thrombosis (CVT) is a rare but potentially fatal disease in pediatric age with an important morbimortality. In adults several factors have been associated with worse outcomes, however there are still few studies in children. This study aims to identify risk factors associated with clinical manifestations and long-term sequelae in pediatric CVT. Methodsː Retrospective analysis of pediatric inpatients admitted to a tertiary-care hospital due to CVT between 2008 and 2020. Resultsː 54 children were included, 56% male, median age of 6.5 years-old (9 months - 17.3 years-old). Permanent risk factors were identified in 13 patients (malignancy – 8; hematologic condition – 5) and transient risk factors in 47, including head and neck infections (57%) and head trauma (15%). Multiple venous sinuses involvement was present in 65% and the deep venous system was affected in four patients. 17% had intracranial hemorrhage and 9% cerebral infarction. 64% of patients with multiple venous sinuses involvement presented with severe clinical manifestations: impaired consciousness; intracranial hypertension; acute symptomatic seizures or focal deficits. Regarding long-term prognosis, 6 patients had major sequelae: epilepsy (n=3); sensor-motor deficits (n=2) and cognitive impairment (n=3). Permanent risk factors were associated with severe clinical manifestations (p=0.043). Cerebral infarction and intracranial hemorrhage were associated with major sequelae (p=0.006 and p=0.03, respectively, adjusted for age and sex).

Hyperglycemia is associated with abnormalities of lipoproteins. The aim of this study was to analyze, in patients with Type 1 Diabetes (T1D), the association of glycemic control with lipid profile, focusing on glycemic variability and time in range obtained from Continuous Glucose Monitoring (CGM). We performed a retrospective cohort in patients with T1D. We analyzed clinical parameters, HbA1c, CGM and lipid profile in two moments 6 to 18 months apart. We evaluated the association of HbA1c and CGM metrics with lipid profile in cross-sectional (n = 242) and longitudinal (n = 90) analyses. The mean age of the study population was 36.6 ± 12.6 years, 51.7% were male, and the mean diabetes duration was 16.8 ± 10.3 years. In the cross-sectional analysis, higher HbA1c, higher glucose management indicator (GMI), higher time above range and lower time in range were associated with higher triglyceride levels. In the longitudinal analysis, an increase in time below range was associated with a decrease of HDL cholesterol. In both analyses, an increase in the coefficient of variability (CV) was associated with a significant decrease of HDL cholesterol. HbA1c and CGM were not associated with total cholesterol or LDL cholesterol. We observed a negative association between CV and HDL cholesterol levels and a positive association between hyperglycemia metrics and triglyceride levels. These findings suggest that CGM parameters may be a helpful tool to guide the improvement of both glycemic control and lipid profile in T1D.

Background Frailty and sarcopenia have been extensively studied in heart failure (HF) patients, but their coexistence is unknown. The aim of this work is to describe the coexistence of these conditions in a sample of HF outpatients and its association with the use of medication and left-ventricular ejection fraction. Methods Participants in this cross-sectional study were recruited from a HF outpatients’ clinic in northern Portugal. Frailty phenotype was assessed according to Fried et al. Sarcopenia was evaluated according to the revised consensus of the European Working Group on Sarcopenia in Older People. Results A total of 136 HF outpatients (33.8% women, median age 59 years) integrated this study. Frailty and sarcopenia accounted for 15.4% and 18.4% of the sample, respectively. Coexistence of frailty and sarcopenia was found in 8.1% of the participants, while 17.6% had only one of the conditions. In multivariable analysis (n = 132), increasing age (OR = 1.13;95%CI = 1.06,1.20), being a woman (OR = 65.65;95%CI = 13.50, 319.15), having heart failure with preserved ejection fraction (HFpEF) (OR = 5.61; 95%CI = 1.22, 25.76), and using antidepressants (OR = 11.05; 95%CI = 2.50, 48.82), anticoagulants (OR = 6.11; 95%CI = 1.69, 22.07), furosemide (OR = 3.95; 95%CI = 1.07, 14.55), and acetylsalicylic acid (OR = 5.01; 95%CI = 1.10, 22.90) were associated with increased likelihood of having coexistence of frailty and sarcopenia, while using statins showed the inverse effect (OR = 0.06; 95%CI = 0.01, 0.30). Conclusions The relatively low frequency of coexistence of frailty and sarcopenia signifies that each of these two conditions still deserve individual attention from health professionals in their clinical practice and should be screened separately. Being a woman, older age, having HFpEF, using anticoagulants, antidepressants, loop diuretics and acetylsalicylic acid, and not using statins, were associated with having concomitant frailty and sarcopenia. These patients can potentially benefit from interventions that impact their quality of life such as nutritional and mental health interventions and exercise training.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) infection and subsequent coronavirus (20)19 disease (COVID‐19)‐related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID‐19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS‐CoV‐2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow‐up was 52 days for the entire cohort and 83 days for survivors. Three‐hundred and three patients died (24%) and COVID‐19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 10 ⁹ /L was found to be protective. This data suggests that MM patients remain at risk of SARS‐CoV‐2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

Introduction. Pheochromocytoma is a rare neoplasia arising from the adrenal medulla that secretes catecholamines. Those afflicted by this condition can present a wide range of symptoms. One of the most common is paroxysmic hypertension. Interestingly, although rare, some patients present with shock. We describe two cases of pheochromocytoma in which the initial presentation was shock. Case 1. 49 year-old woman, with a history of resistant hypertension, presented to the emergency department with thoracic pain and fever. EKG, echocardiogram (ECC), and myocardial necrosis markers were compatible with Takotsubo syndrome (TS). CT demonstrated a staghorn calculus, hydronephrosis, and signs compatible with xanthogranulomatous pyelonephritis in the right kidney. Additionally, and incidentally, it revealed a 60 mm nodule on the right adrenal gland. Piperacillin/tazobactam was started immediately, and the patient was submitted to urgent upper urinary tract drainage. This procedure was complicated by a cardiorespiratory arrest that was treated with adrenaline administration. The patient was admitted to the ICU due to multifactorial shock and started alpha and, posteriorly, beta blockage. Biochemical adrenal incidentaloma endocrinologic study was negative (under hemodialysis). Multiorgan failure progressively improved. After 2 weeks, the patient was submitted to a laparoscopic transperitoneal right adrenalectomy. No complications were reported. Histological analysis revealed a pheochromocytoma. Case 2. 28-year-old woman presented to the emergency department with headaches and nausea. Vitals were compatible with shock. CT revealed an incidental 72 mm mass on the right adrenal. EKG, ECC, and myocardial necrosis markers were compatible with TS. The patient was started on alpha and, posteriorly, beta blockage. Adrenal incidentaloma endocrinological study demonstrated high urinary catecholamines. Right transperitoneal adrenalectomy was performed. No complications were noted. Histological analysis revealed a pheochromocytoma. Conclusion. Pheochromocytoma can present with complex, enigmatic, and rare clinical pictures. Clinicians should be wary of the possibility of this diagnosis when managing adrenal masses.

Objectives. Hereditary transthyretin amyloidosis caused by the (ATTRv) p. Val142Ile variant is a common cause of cardiac amyloidosis among Western African countries and Afro-Americans populations. However, in recent years, Caucasian patients have been identified in greater numbers, raising the question of whether this variant has been undeappreciated in this population. We now have new cases of cardiac amyloidosis caused by the p.Val142Ile from a center in northern Portugal. In addition, we reviewed and discussed the published data concerning p.Val142Ile in Caucasians. Design. Patients diagnosed with cardiac amyloidosis underwent genetic testing using TTR gene sequencing and their relatives were recommended for genetic counsellingand testing if a pathogenic TTR variant was found. In our center, we reviewed the clinical data of patients who had the p.Val142Ile variant. A review of published cases of p.Val142Ile in Caucasians was also performed, to which our data was compared. Results. We found three ATTRv patients with the p.Val142Ile variant (one homozygotic), all Caucasian males with a median age at diagnosis of 69 years old. All of them had heart failure and arrhythmias. During the follow-up period, two patients died. There were 47 unrelated unrelated Caucasian cases of ATTRv p.Val142Ile variant reported worldwide until May 2022. Conclusions. Our findings add to the mounting evidence that the global prevalence of p.Val142Ile is likely understated. This highlights the importance of the systematic screening of the TTR gene in amyloidosis and phenocopies, as well as larger epidemiologic studies to determine the true ATTRv p.Val142Ile prevalence in non-African communities.

Background STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat‐to‐target (T2T) versus standard of care (SoC). Aim To assess the efficacy of ustekinumab extended treatment in a long‐term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes. Methods Adults with moderately‐to‐severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70‐point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol‐defined ustekinumab dose frequency escalation/de‐escalation was applied based on achieving endoscopic remission and corticosteroid‐free clinical remission. Achieving corticosteroid‐free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non‐responder imputation. Results Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de‐escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals. Conclusion STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit–risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm‐driven dose adjustment including de‐escalation.

Skene’s gland duct cysts are benign, asymptomatic bulging interlabial masses that are rarely identified in female newborns. The aetiology is unknown, but it is commonly associated with in utero maternal oestrogen exposure or obstruction or stenosis of the gland duct. We report three unrelated cases of neonatal Skene’s gland duct cysts that resolved spontaneously without the need for surgical intervention.

Purpose Persistent diabetic macular edema (DME) remains a problem in clinical practice, with many patients having a suboptimal response to the standard of care (SOC). Evidence supports the long-term efficacy of intravitreal fluocinolone acetonide (FAc) implant (ILUVIEN ® ) in patients that have responded sub-optimally, although there is still scarce data from real-world Portuguese practices. We aimed to monitor the current SOC in selected Portuguese practices prior to FAc implantation and then assess the long-term effectiveness and safety of the FAc implant. Settings The study included patient data from five Portuguese public hospitals. Design This was a non-interventional, multicenter audit of data collected from Retina.pt registry from patients with persistent or recurrent DME despite treatment. Methods Outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP). Results were compared at regular times over 36 months. Results This study included 222 eyes from 152 patients. A significant decrease in BCVA (P < 0.001) and a significant increase in CMT (P = 0.013) were observed prior to FAc. A significant increase in BCVA was registered at 6 months after FAc implant administration (P < 0.001), which was maintained during follow-up. No relevant changes in IOP were observed. Treatment burden was reduced as a result of treatment with FAc (P < 0.001 for anti-VEGF, corticosteroids, or both treatments) in the full population. Conclusions In Portuguese practice, data showed that pre-FAc implantation, some patients did not respond to SOC treatment and/or they were undertreated. Following FAc implant administration, there were rapid, sustained, long-term visual and anatomical improvements, and a marked reduction in treatment burden.

Introduction: Kidney transplantation is the preferred treatment for end-stage renal disease, but organ scarcity can result in long waiting times. Living-donor kidney transplantation offers an alternative to deceased donation, but HLA or AB0 incompatibility can pose a significant obstacle. This study aimed to show the results achieved by a portuguese hospital since its integration into an international cross-over program, the South Alliance for Transplants (SAT). Methods: The SAT program was founded in 2017 and is composed of ten Spanish hospitals, three Italian hospitals and one Portuguese hospital. The program runs every 4 months and enrolled only pairs that were incompatible. Organ transportation is carried out in partnership with the Portuguese Air Force. Results: Three distinct cross-over kidney transplants were performed in partnership with three Spanish hospitals, culminating in the transplantation of three Portuguese patients out of a total of seven patients. The first swap was performed in March 2020, at the beginning of the COVID-19 pandemic, in partnership with two Portuguese and one Spanish hospital. It involved one donor/recipient pair from each country, with AB0 incompatibility between the Portuguese donor and recipient, and no complications were reported. The second swap occurred in December 2021, with three donor/recipient pairs (one Portuguese, where the recipient presented anti-donor antibodies and positive crossmatch with the potential donor, and two from two Spanish hospitals). It was complicated by type-IB cellular rejection in the Portuguese recipient, one week after transplantation, which was treated with corticosteroid therapy. The third swap, also in December 2021, involved two donor/recipient pairs (one Portuguese and one Spanish). It was complicated by delayed renal function due to acute tubular necrosis (histological diagnosis) in the Portuguese recipient. At follow-up, the patients‘ serum creatinine levels were within normal limits, and no other unexpected outcomes were recorded. Conclusion: SAT program has allowed some successful cross-over kidney transplants, probably improving the outcomes of kidney transplantation in Portugal. The expansion of such programs may contribute to a more efficient use of the available resources, increasing the number of transplants performed and reducing waiting times

Introdução: O transplante renal é o tratamento preferencial da doença renal crônica terminal, porém, a escassez de órgãos pode resultar em longos tempos de espera. O transplante renal de doador vivo oferece uma alternativa ao doador cadáver, mas a incompatibilidade HLA ou AB0 pode representar um obstáculo significativo. Este estudo teve como objetivo mostrar os resultados alcançados por um hospital português desde sua integração num programa internacional de doação cruzada, o South Alliance for Transplants (SAT). Métodos: O programa SAT foi fundado em 2017 e é composto por dez hospitais espanhóis, três hospitais italianos e um hospital português. O programa ocorre a cada 4 meses e inscreve apenas pares que são incompatíveis. O transporte de órgãos é realizado em parceria com a Força Aérea Portuguesa. Resultados: Foram realizados três cruzamentos distintos em parceria com três hospitais espanhóis, culminando no transplante de três doentes portugueses de um total de sete doentes. O primeiro cruzamento foi realizado em março de 2020, no início da pandemia de COVID-19, com a parceria de dois hospitais portugueses e um hospital espanhol, envolvendo 1 par doador/recetor de cada país, em que o português apresentava incompatibilidade AB0 e onde não se registraram complicações. O segundo ocorreu em dezembro de 2021 com 3 pares doador/receptor (1 português em que o recetor apresentava anticorpos anti-dador e crossmatch positivo com o potencial doador; e 2 de dois hospitais espanhóis), complicado com rejeição celular tipo-IB uma semana após o transplante no receptor português, tratada com corticoterapia. O terceiro cruzamento ocorreu também em dezembro de 2021 com 2 pares doador/recetor (1 português e 1 espanhol), complicado com atraso na função renal por necrose tubular aguda (diagnóstico histológico) na receptora portuguesa. Durante o follow-up, os níveis de creatinina sérica dos doentes mantiveram-se dentro dos limites normais, e não foram registradas outras intercorrências. Conclusão: O programa SAT permitiu a realização de alguns transplantes renais cruzados bem-sucedidos, provavelmente melhorando os resultados do transplante renal em Portugal. A expansão de programas semelhantes pode contribuir para um uso mais eficiente dos recursos disponíveis, aumentando o número de transplantes realizados e reduzindo os tempos de espera.

Background Nocardiosis is a rare opportunistic infection with increasing incidence. Given its rarity, data on the prognosis and distribution are scarce and essential. Methods Retrospective study reviewing all nocardiosis cases diagnosed at our tertiary care hospital from January 2019 to January 2023. Results A positive Nocardia spp. culture was identified in 20 patients. Nocardia isolation was considered colonization in 2 patients, but the other 18 cases were considered as disease, 6 (33.3%) of which were classified as disseminated nocardiosis (DN). The mean age was 64.0±14.05 years-old and 75% were males. One or more immunosuppressive conditions were identified in 70% of patients, including diabetes mellitus (n=9), active solid tumors (n=3), autoimmune diseases (n=3) and HIV infection with CD4+ < 200 cel/uL (n=2). Among the immunocompromised patients, 28,6% were being treated with high-dose corticosteroid therapy. The lung was the most common site of infection (85%) and most cultures were initially retrieved for lower respiratory tract samples (85%) evaluated for mycobacteria in modified Middlebrook 7H9 Broth. Lymphopenia was observed in 38.9% of patients.The most frequently isolated species were N.nova/africana (n=7), N.cyriacigeorgica (n=4) and N.pseudobrasiliensis (n=3). N.cyriacigeorgica was identified in the two cases considered colonization. Most patients (94.4%) were treated with antimicrobials, 50.0% in monotherapy and 44.4% in combination therapy. The most frequently prescribed antibiotics were co-trimoxazole (94.4%), imipenem (22.2%) and linezolid (16.7%). Selected antimicrobial agents were generally effective, with linezolid and co-trimoxazole having the highest susceptibility rates (100% susceptibility). The median [IQR] duration of treatment was 238 [45–720] and 170 [5–360] days for localized and DN, respectively. The overall one- year case fatality was 25% and was higher in patients with DN (80%). Conclusion Nocardiosis is an uncommon but emerging disease which can occur both in immunocompetent and immunocompromised patients. The present study reports a case series on Nocardiosis from Portugal and provides important information of this disease. As the outcomes are poor, early recognition and prompt treatment are essential to improve the outcome. Disclosures All Authors: No reported disclosures

Background/ objective To evaluate the association of CGM parameters and HbA1c with diabetes complications in patients with Type 1 Diabetes (T1D). Methods Patients with T1D using the CGM system Freestyle Libre were included in this analysis. The association of CGM-metrics and HbA1c with diabetes complications (any complication, microvascular complications, or macrovascular complications) was assessed using logistic regression unadjusted and adjusted for age, sex, and diabetes duration (model 1), and further adjusted for hypertension and dyslipidemia (model 2). Results One hundred and sixty-one patients with T1D were included. The mean (± SD) age was 37.4 ± 13.4 years old and the median T1D duration was 17.7 ± 10.6 years. Time in range (TIR) was associated with any complication and microvascular complications in the unadjusted model and in the adjusted models. TIR was associated with retinopathy in the unadjusted model as well as in model 1, and was associated with macrovascular complications only in the unadjusted model. HbA1c was associated with any complications, microvascular complications, and retinopathy in the unadjusted model but not in the adjusted models. HbA1c was associated with macrovascular complications in the unadjusted model and in the adjusted model 1. Conclusions In this cross-sectional analysis of patients with T1D using intermittent scanned CGM, TIR, and HbA1c were associated with complications of diabetes. TIR may be a better predictor than HbA1c of any complication and microvascular complications, while HbA1c may be a better predictor of macrovascular complications.

Background Mpox virus was declared a public health emergency of international concern by the World Health Organization in July 2022. The full range of clinical manifestations of this emerging infectious disease continues to be elucidated. Methods We present a case series and literature review of patients with mpox myocarditis and pericarditis, including demographics, clinical symptoms, diagnostic and management strategies, and outcomes. Results We identified 13 patients aged 21-51 (median 32) years with polymerase chain reaction-confirmed mpox and myopericarditis (n=3), pericarditis (n=1), or myocarditis (n=9), from 6 countries on 3 continents. All but one were men. One was HIV-positive (viral load undetectable) and 4 were on HIV pre-exposure prophylaxis. None had prior cardiac disease and 3 used tobacco. Most acquired mpox via sexual contact; one heterosexual patient reported non-sexual close contact. Cutaneous/mucosal lesions occurred in 11/13 patients, and fever in 11/13. Where reported, cardiac symptom onset was 2-8 (median 5.5) days after mpox illness onset. C-reactive protein ranged from 9.3-154.5 (median 52.6) mg/L. Diagnosis of myocarditis/myopericarditis was based on symptoms (chest discomfort 11/12, dyspnea 3/4), elevated troponin (range 165-21200 ng/L, peaking 1-2 days after cardiac symptom onset), supportive electrocardiogram (ECG) findings (diffuse or territorial ST elevation, T-wave inversions, and/or non-specific ECG changes 9/12), and/or cardiac imaging findings (pericardial effusion 1/12, left ventricle [LV] abnormalities on echocardiogram 4/12, abnormal cardiac MRI in 7/7 done acutely). In the pericarditis case, ECG showed widespread ST elevation and echocardiogram showed hyperdynamic LV. Treatments included ASA or non-steroidal anti-inflammatory drugs (n=7), tecovirimat (n=5), colchicine (n=4), ACE-inhibitors (n=3) and bisoprolol (n=3). All were hospitalized, with lengths of stay of 4-10 days, and at least 3 patients required intensive care. Cardiac symptom recovery occurred within 1-3 days of admission; in at least 1 patient symptoms continued beyond 1 month. Conclusion Mpox is rarely associated with myocarditis and/or pericarditis, with cardiac symptoms beginning on day 2-8 after illness onset. Long-term outcomes require further study. Disclosures Cécile Tremblay, MD, Association canadienne de protection médicale: Expert Testimony|Astra-Zeneca: Advisor/Consultant|Astra-Zeneca: Honoraria|Canadian Institutes of Health Research: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Honoraria|Medicago: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|National Institute of Health: Grant/Research Support|Sanofi: Advisor/Consultant Darrell H. S. Tan, MD PhD, Abbvie: Grant/Research Support|Gilead: Grant/Research Support|Glaxo Smith Kline: Grant/Research Support