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The Prognostic Value of Histopathological Classifications in ANCA-Associated Vasculitis
No full textRenal involvement is a common and severe feature of ANCA-associated vasculitis, leading to end-stage kidney disease and death in a considerable number of patients. One of the challenges of ANCA-associated glomerulonephritis is to establish histological features of prognostic value, in order to identify patients who will benefit of immunosuppression.
Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. In 2010, Berden et al (J Am Soc Nephrol. 2010; 21: 1628-36) proposed a histopathologic classification based only on glomerular morphology, which is of prognostic value for short-term and long-term renal outcomes. However, over the last years, the results of several studies using multivariable approaches have suggested that the proposed histopathologic classes alone might not be sufficient to predict renal outcome. In order to refine the prognosis of patients with ANCA-associated vasculitis, in 2018, Brix et al (Kidney Int. 2018;94:1177-88) proposed the Renal Risk Score, based on clinical and pathological parameters.
In this review, we discuss the prognostic value of the Histopathologic Classification and the Renal Risk Score and their role in routine clinical practice.info:eu-repo/semantics/publishedVersio
Massa Occipital Volumosa: Foliculite Queloidial da Nuca
No full textinfo:eu-repo/semantics/publishedVersio
Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice
No full textObjectives: To identify the preoperative risk factors for prediction of non-transplantable recurrence (NTR) after tumor resection for early-stage hepatocellular carcinoma (HCC) to assist in patient selection relative to upfront liver resection (LR) versus liver transplantation (LT).
Methods: Patients who underwent curative resection for transplantable HCC and chronic liver disease were identified from an international multi-institutional database. NTR was defined as recurrence beyond the Milan or UCSF criteria, and the preoperative risk factors of NTR were investigated.
Results: Among 293 patients with transplantable HCC within Milan criteria and 320 within UCSF criteria, 113 (38.6%) and 131 (40.9%) patients developed tumor recurrence, respectively. Among patients who recurred, NTR was present in 32 (28.3%) patients within Milan and 35 (26.7%) within UCSF criteria. When either Milan or UCSF criteria was adopted, three preoperative risk factors including liver cirrhosis, tumor size > 3 cm, and multiple lesions were consistently identified as risk factors associated with NTR after curative resection. By summing up the three factors, a scoring model was established and the incidence of NTR among patients with 0, 1 or ≥ 2 risk factors incrementally increased from 4.5%, 13.3% to 20.5% when Milan criteria was used, and from 4.5%, 12.4% to 33.9% when UCSF criteria was adopted. The model demonstrated very good discriminatory power on internal validation (n = 5,000) (c-index 0.689 for Milan criteria, and 0.715 for UCSF criteria).
Conclusions: Whereas surgical resection may be optimal first-line treatment for patients with no or one risk factor, patients with ≥ 2 risk factors should be considered for upfront liver transplantationinfo:eu-repo/semantics/publishedVersio
Imipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies)
No full textImipenem-relebactam is a novel β-lactam-β-lactamase inhibitor combination. We evaluated the in vitro activity of imipenem-relebactam and comparators against Enterobacterales clinical isolates recovered in 8 Spanish and 11 Portuguese intensive care units (ICUs) (SUPERIOR, 2016-2017; STEP, 2017-2018). Overall, 747 Enterobacterales isolates (378 Escherichia coli, 252 Klebsiella spp., 64 Enterobacter spp., and 53 other species) were prospectively collected from ICU patients with complicated intraabdominal (cIAI), complicated urinary tract (cUTI), and lower respiratory tract (LRTI) infections. MICs were determined (ISO-broth microdilution), and whole-genome sequencing (WGS) was performed in a subset of isolates displaying susceptible and resistant imipenem-relebactam MICs. Imipenem-relebactam (98.7% susceptible) showed similar activity to ceftazidime-avibactam (99.5% susceptible) and higher than ceftolozane-tazobactam (86.9% susceptible). Imipenem-relebactam was inactive against 1.3% (10/747) isolates, all of them due to carbapenemase production (9 K. pneumoniae and 1 E. cloacae). Imipenem-relebactam was active against 100% of extended-spectrum β-lactamase (ESBL)-E. coli and ESBL-Klebsiella spp. isolates and 80.4% of carbapenemase-Klebsiella spp. producers. Carbapenemase genes were confirmed by WGS in 41 Klebsiella spp.: OXA-48 (20/41), KPC-3 (14/41), OXA-181 (4/41), NDM-1 (1/41), OXA-48 + VIM-2 (1/41), and KPC-3 + VIM-2 (1/41). In Klebsiella spp. isolates, relebactam restored imipenem susceptibility in all KPC-3 producers, and resistant isolates (7/41) were mostly OXA-48 + CTX-M-15-K. pneumoniae high-risk clones (7/9). Intercountry differences were detected as follows: OXA-48 (17/21) was dominant in Spain, unlike KPC-3 (14/15) in Portugal. Imipenem-relebactam was 100% active against CTX-M-15-ST131-H30Rx-E. coli high-risk clone, predominant in both countries. Our results depict the potential role of imipenem-relebactam in ICU patients with cIAIs, cUTIs, and LRTIs due to wild-type ESBL- and carbapenemase-producing Enterobacterales, particularly KPC producers. IMPORTANCE We comparatively evaluate the in vitro activity of a drug combination consisting of a carbapenem (imipenem) and a novel inhibitor of beta-lactamases (relebactam), a mechanism that destroys beta-lactam antibiotics. We assess the activity against a collection of Enterobacterales clinical isolates recovered from difficult-to-treat infections in patients admitted to different intensive care units in Portugal and Spain. Imipenem-relebactam shows excellent activity in avoiding common resistance mechanisms in this setting, such as extended-spectrum beta-lactamases and carbapenemases widely distributed, including KPCs. We show few resistant isolates (<2%). Molecular characterization by whole-genome sequencing shows that most of the resistant isolates produced specific carbapenemase, such as OXA-48 or metalo-betalactamases. Our study updates the activity of imipenem-relebactam in light of current epidemiology in a hospital setting in which the use of this combination is needed due to the presence of infections due to multidrug-resistant isolates.info:eu-repo/semantics/publishedVersio
The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: an Update
No full textPheochromocytoma and paragangliomas (PPGL) are rare neuroendocrine tumors. In some patients they exhibit malignant behavior characterized by the presence of metastases, limiting treatment options and survival rates. Therapeutic options are limited to surgery, localized radiotherapy, and a few systemic therapies. However, in several recent studies, non-coding RNA molecules are gaining increasing attention as markers of malignancy for PPGL. The understanding of PPGL development molecular mechanisms has improved in the last years, with some of the epigenetic regulatory mechanisms such as DNA and histones methylation, being better understood than RNA-based mechanisms. Metabolome deregulation in PPGL, with increased synthesis of molecules that facilitated tumor growth, results from the activation of hypoxia signaling pathways, affecting tumorigenesis. In addition, the assessment of these metabolites can be useful for the management of these tumors. This review summarizes recent discoveries linking metabolome and non-coding RNA to PPGL and their relevance for diagnosis and therapeutics.info:eu-repo/semantics/publishedVersio
In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU)
No full textPhenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic TechnologyTM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (-46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.info:eu-repo/semantics/publishedVersio
A Systemic Review of Endocardial Left Ventricular Pacing
No full textBackground: Endocardial left ventricular pacing is an alternative technique used in cardiac resynchronization therapy (CRT), when placement of a left ventricular lead is not possible via the coronary sinus or in non-responders to conventional CRT.
Objectives: To review the evidence regarding the efficacy and safety of endocardial left ventricular pacing.
Methods: Systematic research on Medline (PubMed), ClinicalTrials.gov and Embase with the terms "endocardial left ventricular pacing", "biventricular pacing" or "endocardial left pacing" was performed with the identification of 1038 results. Eleven studies with endocardial left ventricular pacing patients were included, independent of the technique being applied to naïve CRT patients or con non-responders to conventional CRT. The end-point of this analysis was the impact of endocardial left ventricular pacing techniques regarding New York Heart Association (NYHA) functional classification, left ventricular ejection fraction (LVEF) and QRS width, and the occurrence of complications Mean differences (MD) and confidence interval (CI) was used as a measurement of treatment.
Results: A total of 560 patients were included, with different techniques used (trans-atrial septal technique, trans-ventricular septal technique and transapical technique). Significant improvement was registered in NYHA class (MD 0.73, CI 0.48-0.98, p<0.00001, I2 = 87%), LVEF (MD -7.63, CI -9.93 - -5.33, p<0.00001, I2 = 69%) and QRS width (MD 29.25, CI 9.99-48.50, p<0.00001, I2 = 91%). Several complications were reported after the procedure, 11 pocket infections, 22 transient ischemic attacks, 18 ischemic strokes, 41 thromboembolic events, among other complications. The mortality rate during the follow-up was 20.54%.
Conclusion: Left ventricular endocardial pacing is a feasible alternative to conventional CRT, with clinical, electrocardiographic and echocardiogrphic improvement. However, first data regarding this procedure was associated with significant complications rates.info:eu-repo/semantics/publishedVersio
Allergen Immunotherapy in MASK‐Air Users in Real‐Life: Results of a Bayesian Mixed‐Effects Model
No full textBackground: Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real-life studies.
Objective: To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK-air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT.
Methods: We assessed the MASK-air® data of European users with self-reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales-VASs), and a combined symptom-medication score (CSMS). We applied Bayesian mixed-effects models, with clustering by patient, country and pollen season.
Results: We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT-tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = -12.1;-2.8), lower VAS Work (average difference = 5.0; 95%CrI = -8.5;-1.5), and a lower CSMS (average difference = 3.7; 95%CrI = -9.3;2.2). When compared to SCIT, SLIT-tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = -17.2;-2.8), lower VAS Work (average difference = 7.8; 95%CrI = -15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = -18.5;0.2).
Conclusion: In patients with grass pollen allergy, SLIT-tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally-harmonised standards for performing and reporting real-world data in AIT are needed to better understand its 'real-world' effectiveness.info:eu-repo/semantics/publishedVersio
Custos Diretos de Internamento por COVID-19 num Centro Hospitalar Universitário Português
No full textBackground: The COVID-19 pandemic has posed greater financial pressure on health systems and institutions that had to respond to the specific needs of COVID-19 patients while ensuring the safety of the diagnosis and treatment of all patients and healthcare professionals. To assess the financial impact of COVID-19 patients admitted to hospitals, we have characterized the cost of COVID-19 admissions, using inpatient data from a Portuguese Tertiary Care University Centre.
Methods: We analysed inpatient data from adult patients di agnosed with COVID-19 who were admitted between March 1, 2020 and May 31, 2020. Admissions were eligible if the ICD-10-CM principal diagnosis was coded U07.1. We excluded admissions from patients under 18 years old, admissions with incomplete records, admissions from patients who had been transferred to or from other hospitals or those whose
inpatient stay was under 24 h. Pregnancy, childbirth, and puerperium admissions were also excluded, as well as adsions from patients who had undergone surgery. Results: We identified 223 admissions of patients diagnosed with COVID-19. Most were men (64.1%) and aged 45–64 years (30.5%). Around 13.0% of patients were admitted to intensive care units and 9.9% died in hospital. The average length of hospital stay was 12.7 days (SD = 10.2) and the average estimated cost per admission was EUR 8,177 (SD = 11,534), which represents more than triple the inpatient base price (EUR 2,386). Human resources accounted for the highest proportion of the total costs per admission (50.8%). About 92.4% of the admissions were assigned to Diagnosis Related Group (DRG) 723, whose inpatient price is lower than COVID-19 inpatient costs for all degrees of severity. Conclusion: COVID-19 admissions represent a substantial financial bur den for the Portuguese NHS. For each COVID-19 hospitalized patient it would have been possible to treat three other hos pitalized patients. Also, the price set for DRG 723 is not adjusted to the cost of COVID-19 patients. These findings highlight the need for additional financial resources for the health system and, in particular, for hospitals that have treated high volumes of hospitalized patients diagnosed with COVID-19.info:eu-repo/semantics/publishedVersio
Protocol-Based Cardiotoxicity Monitoring in Hydroxychloroquine Medicated COVID-19 Pediatric Patients
No full textIntroduction/objectives: By May 2020, SARS-CoV-2 had caused more than 400 000 deaths worldwide. Initially, hydroxychloroquine was a treatment option for COVID-19. More recent studies have questioned its safety and efficacy and, until stronger evidence is available, it was suspended from therapy protocols. We describe our experience treating COVID-19 Portuguese pediatric patients with hydroxychloroquine, having applied a protocol for monitoring cardiac toxicity.
Methods: An observational retrospective study of COVID-19 pediatric patients, admitted from March to April 2020 and treated with hydroxychloroquine. Cardiotoxicity was assessed using ECG recordings and corrected QT-time (QTc). Patients were classified into risk-groups depending on QTc value: normal, slightly elevated or severely elevated (>500 ms).
Results: Total of 14 patients, with a median age of 10 years [four months; 17 years], treated with hydroxychloroquine for a median of five days. Hydroxychloroquine was used in monotherapy in six patients (mainly mild disease with comorbidities), and in association with lopinavir/ritonavir (3) and azithromycin (5) in moderate to severe disease. Other QT-prolonging therapies were used in five patients: oseltamivir (3), omeprazole (1), morphine (1) and ketamine (1). At 48 hours of treatment, two patients temporarily suspended hydroxychloroquine due to QTc prolongation (>500 ms). All patients completed the whole treatment. No other side effects or deaths occurred.
Conclusion: Clinical trials are evolving to define hydroxychloroquine effectivity and safety. Our considerable pediatric population supports the need for cardiotoxicity monitoring during therapy but suggest its use seems to be safe in COVID-19 pediatric patients, even in association with other QT-prolonging therapies.info:eu-repo/semantics/publishedVersio