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The Microevolutionary Trajectory of Endemic Multidrug-Resistant Tuberculosis Strains in Portugal Toward Increased Drug Resistance Levels and its Clinical Significance.
Publication . Gomes, Pedro; Paixão, Paulo; Maltez, Fernando; Brum, Laura; Phelan, Jody E; Campino, Susana; Clark, Taane G; Viveiros, Miguel; Portugal, Isabel; Perdigão, João
Portugal has one of the highest incidence rates of tuberculosis (TB) in Western Europe and, historically, multidrug-resistant (MDR) cases have been strongly associated with strains pertaining to the endemic Q1 and Lisboa3 clades. Notwithstanding, the contribution of drug resistance-associated allelic configurations in these clades to differing levels of drug resistance and their relationship with drug efficacy has yet to be uncovered. A representative sample of the drug-resistant population in Portugal, comprised of 40 clinical strains were subjected to whole genome sequencing for characterization of allelic combinations of drug resistance-associated mutations and their minimum inhibitory concentrations for 12 anti-TB drugs was determined. Pharmacokinetic (PK) models were generated to ascertain the maximum concentration to which each drug remains efficacious. Drug resistance levels were determined and compared between different allelic configurations. Double and mutation genotypes contributed with increased isoniazid and ethambutol resistance levels compared with single mutation configurations, respectively. Significant differences in drug resistance levels were observed between phylogenetic groups for rifamycin, streptomycin and ethionamide, largely explained by the presence/absence of unique high-level resistance-associated genotypes. The PK models for isoniazid and moxifloxacin suggest an increase in dosage to be ineffective against strains harboring high-level resistance-conferring double mutations and mutations. Cycloserine and para-aminosalicylic acid are the only drugs predicted to remain efficacious against the majority of tested strains, while the effectiveness of newer drugs like bedaquiline, pretomanid and delamanid have yet to be uncovered. Proper diagnosis of drug resistance-associated mutations provides invaluable insights into the treatment of TB, as different allelic configurations lead to differing drug resistance levels, often rendering drugs ineffective.
Preventing Laboratory-Acquired Infection: Literature Review and Case-Based Post-Exposure Prophylaxis Proposal.
Publication . Póvoas, Diana; Demengeot, Jocelyne; Maltez, Fernando
Occupationally acquired cases of the intracellular parasite have been reported, even though there is uncertainty on which infection prevention measures should be implemented in such event. We report a clinical case of laboratory-acquired toxoplasmosis and propose a protocol for post-exposure prophylaxis, given there are no formal guidelines. In this community case study, we describe the management and prevention protocol following an occupational laboratory exposure by a healthy 30-year-old -seronegative female researcher who suffered an accidental needle puncture with a sample containing a genetically modified hypervirulent strain. Post-exposure prophylaxis (PEP) with trimethoprim-sulfamethoxazole was implemented for 4 weeks, during which seroconversion occurred, without any accompanying symptoms. IgM and IgG positivity was observed 21 and 50 days after exposure, respectively, using a validated commercial electrochemiluminescence immunoassay (ECLIA, Roche). Follow-up was maintained for 1 year, during which the patient remained asymptomatic. This report highlights the importance of special care, surveillance and decision on the need for PEP upon occupational laboratory accidental exposure to . Since there are no guidelines on what the optimal PEP regimen should be, after a literature review, we propose a PEP occupational safety protocol to be implemented in laboratories that handle samples containing , either in clinical or research setting.
Prediction of Response to Cardiac Resynchronization Therapy Using Electrocardiographic Criteria: a Systematic Review.
Publication . Dias Costa, Paulo; Bessa, João Pedro; Canelas Pais, Mariana; Ferreira-Santos, Daniela; Montenegro Sá, Fernando; Monteiro-Soares, Matilde; Hipólito-Reis, António; Martins Oliveira, Mário; Pereira Rodrigues, Pedro
Background: Cardiac resynchronization therapy (CRT) is an established therapeutic option for heart failure, but despite careful selection around 30% of the patients still do not respond to this therapy. The standard electrocardiogram (ECG) is a practical and inexpensive tool to assess potential responders to CRT but with conflicting evidence regarding the value of different ECG parameters. As such, we conducted a systematic review of real-world studies to assess the value of pre-implantation standard ECG parameters in predicting response to CRT.
Methods: We searched on PubMed, Scopus, and Web of Knowledge online databases to identify analytic studies and synthesized results through evidence tables.
Results: Sixty-two eligible articles were included in this review. Traditional predictors of response were QRS duration ≥150 ms and the presence of left bundle branch block morphology. Contemporary ECG parameters, such as the presence of QRS notching or fragmentation, the S wave assessment, the time to intrinsicoid deflection (ID) in lateral leads, and a lead one ratio ≥12 also showed great potential in assessing response to CRT.
Conclusions: This review highlights the promising capability of the standard ECG in predicting response to CRT, particularly when using more contemporary predictors, while emphasizing the necessity for further research to validate the prognostic value of these predictors.
Primaquine-Induced Methemoglobinemia: A Case Report.
Publication . Leite Cruz, Rita; Vieira, César B; Silva, Pedro; Pereira, Rui; Germano, Nuno
Methemoglobinemia is a life-threatening side effect of several drugs, including primaquine. When endogenous counter-oxidative stress mechanisms are overwhelmed, hemoglobin is oxidized to methemoglobin. This "oxygen scavenger" leads to tissue hypoxia, despite adequate alveolar gas exchange. A 47-year-old male under immunosuppression after a reno-pancreatic transplant was admitted to the ICU for respiratory failure following suspected pneumonia (PJP), and empiric treatment was started. After ICU admission, treatment with cotrimoxazole was switched to primaquine due to hematological toxicity. Progressively, the oxygenated hemoglobin fraction declined despite normal PaO levels. Concurrently, methemoglobin levels rose, suggesting primaquine as the culprit. Treatment was switched to pentamidine, and ascorbic acid was administered. Methemoglobin levels subsequently lowered, and oxygen saturation normalized. G6PDH activity levels were within the normal range. Pentamidine was continued for a total of 21 days while the patient slowly recovered. Methemoglobinemia is a rare complication of primaquine treatment with severe consequences. A discrepancy between PaO and the oxygenated hemoglobin fraction should raise awareness of this diagnosis and prompt immediate action.
Proximal Junctional Kyphosis Following Spinal Thoracic Deformity Correction in a Patient with Kabuki Syndrome: A Case Report.
Publication . Nóbrega, João; Almeida, Ricardo; Rasteiro, Pedro; Rosado, João; Botelho, Tiago; Carvalho, Nelson
Introduction: Kabuki syndrome (KS) is a rare congenital disorder characterized by distinctive facial features, intellectual disability, and multiple musculoskeletal anomalies, including scoliosis, kyphosis, and generalized ligamentous laxity. The combination of connective tissue fragility and complex spinal deformity may predispose these patients to post-operative complications, such as proximal junctional kyphosis (PJK), though this association has not previously been reported.
Case report: We report a 15-year-old male with genetically confirmed KS who presented with severe thoracic hyperkyphosis (95°). Posterior spinal fusion and correction were performed, resulting in initial improvement. Within 8 months, the patient developed PJK above the upper instrumented vertebra, requiring multiple revision procedures. Post-operative infection with Staphylococcus aureus and rapid recurrent kyphosis further complicated management. A staged revision strategy, combining halo-gravitational traction followed by extended fusion and careful sagittal realignment, achieved stable correction and functional improvement at 1-year follow-up.
Conclusion: The association between these conditions has, to our knowledge, not yet been reported in literature. This case highlights the multifactorial etiology of PJK in KS, where intrinsic ligamentous laxity, immune dysfunction, and extensive deformity correction converge to increase mechanical vulnerability. Soft-tissue preservation at the upper instrumented level, careful sagittal contouring, and infection control are key preventive strategies. Due to inherent ligamentous laxity and connective tissue abnormalities, patients with KS could be predisposed to proximal junctional failure after spinal deformity correction. Pre-operative recognition of connective tissue and immunologic abnormalities, together with detailed surgical planning, is essential to minimize complications and optimize long-term outcomes.