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Immunotherapy with BCG is an effective and widely used treatment for non-muscle-invasive bladder cancer. BCG sepsis is a rare but life-threatening and frequently not a straightforward complication of this treatment; in cases with a high index of suspicion, anti-bacillary treatment should not wait for laboratory confirmation and be instituted immediately. We report a severe case of BCG sepsis, in which timely diagnosis and initiation of antituberculosis agents enabled a full recovery.

A 64-year-old woman presented with diffuse abdominal pain, postprandial bloating and 5 kg of unintentional weight loss in the last 3 months. She had a previous medical history of nephrectomy due to recurrent pyelonephritis and hypothyroidism. Physical examination revealed only mild tenderness in

Background: In COVID-19, there are no available tools or guidelines for the difficult task of recognizing which patients do not benefit from keeping advanced respiratory support, such as noninvasive ventilation (NIV). Identifying failure is crucial to deliver the best possible care and optimize resources in overloaded healthcare systems. Therefore, this study aimed to build a model that predicts NIV failure and consequent death in COVID-19 patients.Methods: This is a retrospective observational study with critical COVID-19 patients who needed NIV but were not candidates or did not need invasive mechanical ventilation, admitted between 1st October 2020 and 31st March 2021, in a tertiary Portuguese hospital. The measure of interest was NIV failure, defined as COVID-19 related in-hospital death. A binary logistic regression was performed, where the outcome (dead vs alive) was set as the dependent variable. Using the independent variables of the logistic regression a decision tree classification model was implemented. Results: The 103 patients included had a mean age of 66.3 years old (SD=14.9), 38.8% were female and 82.5% autonomous. The developed prediction model was statistically significant (X2= 119.865; p< .001) with an area under the curve (AUC) of 0.994. Higher age, higher number of days with increases on FiO2, higher number of days of maximum expiratory positive airway pressure, lower number of days on NIV, and lower number of days from disease onset to hospital admission were, with statistical significance, associated with increased odds of death. A decision-tree classification model was obtained to achieve the best combination of variables to predict the outcome of interest. Conclusions: This study presents a model to predict death in COVID-19 patients treated with NIV (AUC of 0.994), including easily applicable variables that mainly reflect patients’ evolution during hospitalization. Along with the decision-tree classification model, these original findings have the potential to help clinicians define the best therapeutical approach to each patient and optimize medical resources. However, further research is needed on this subject of treatment failure, not only to understand if these results are reproducible but also, in a broader sense, to help fill this gap in modern medicine guidelines.

A 68-year-old woman presented to the emergency department complaining of both lumbar and left shoulder inflammatory pain, during the past 2 weeks. She had a previous history of chronic kidney disease on regular haemodialysis as well as a superior vena cava syndrome and peripheral vasculopathy

Hereditary myopathy with early respiratory failure is a neuromuscular disease with an autosomal dominant inheritance pattern. Clinical presentation is characterised by proximal and distal muscle weakness, exertional dyspnoea and generalised fatigue. There is no disease-modifying therapy and the prognosis is unknown. Herein we present a case of a 40-year-old woman with long-standing asthenia and apathy and, more recently, daytime sleepiness, dyspnoea and difficulty in walking. A hypercapnic respiratory failure with severe acidemia was identified. The muscle biopsy showed the presence of cytoplasmatic bodies and rimmed vacuoles, suggestive of a hereditary myopathy with early respiratory failure disease. The genetic study confirmed this diagnosis identifying a heterozygous mutation on c.95134T>C (p.Cys31712Arg) in exon 343 in the titin gene. The patient was discharged home under supportive treatment with non-invasive ventilation.

A 63-year-old man, without any history of cutaneous reactions, noticed the spontaneous appearance of a painful, non-pruritic maculopapular hyperpigmented rash on his arms and legs ([figures 1 and 2][1]). Four days after the emergence of the lesions he looked for medical aid since the rash was

Multiple myeloma (MM) can present courses with lytic bone destruction caused by increased osteoclastic activity. These images are of a 64-year-old woman who presented to health services with neck and shoulder pain, anorexia, asthenia and weight loss, with months of evolution and multiple recurrences

The artery of Percheron is a rare anatomical variation that supplies thalamus and the midbrain. A stroke in this area is a rare event. The presentation varies widely, with some bizarre disturbances, like transient episodic loss of consciousness similar to coma, somnolence, cognition and memory impairment and psychosis. We report a case of a patient who presented at the emergency department with a sudden change of consciousness. During the observation, she oscillated reactive state of consciousness with obnubilation similar to coma. The first exams were normal, which include a cranial CT of the brain, and so the patient was kept under observation. The final diagnosis was only possible 24 hours later with cranial CT where an ischaemic lesion on the Percheron territory was identified. This case highlights an unusual clinic and a difficult neuroimaging stroke diagnosis of a rare condition, that is unknown to most of the physicians.

Persistent infection by high-risk human papillomavirus is a necessary cause for cervical cancer. DNA-based human papillomavirus (HPV) assays show high sensitivity but poor specificity in detecting high-grade cervical lesions. Assays detecting mRNA of the oncoproteins E6 and E7 show higher specificity but lack either detection of all high-risk genotypes or the ability to specify the detected genotypes. The aim of this study was to evaluate the clinical performance of the NucliSENS EasyQ HPV assay in comparison with the Hybrid Capture 2 test (HC2) and the CLART Human Papillomavirus 2 assay (CLART), using a clinical cut-off of cervical intraepithelial neoplasia grade 2 or worse. In the 554 studied women, the lowest HPV positivity rate was detected for NucliSENS EasyQ HPV assay (55.1%), while HC2 and CLART showed similar results (HC2: 77.4%; CLART: 78.0%). In comparison with the other tests, the NucliSENS EasyQ HPV assay showed a lower clinical sensitivity (79.3% vs. 96.4% for HC2 and 95.9% for CLART) but a higher clinical specificity (72.6% vs. 42.8% for HC2 and 42.5% for CLART). Detection of E6/E7 mRNA transcripts may provide a higher specificity for cervical intraepithelial neoplasia grade 2 lesions or worse, since the oncogenic potential of HPV infection depends on the over-expression of these two oncoproteins.

Persistent infection with high-risk (HR) human papillomavirus (HPV) types is necessary for cervical cancer development. However, little is known about the influence of multiple HPV infections on cervical lesion risk. The aim of this study was to evaluate the frequency of single and multiple HPV infections in Portuguese women, and to assess the frequency of multiple infections in cervical intraepithelial neoplasia (CIN). HPV prevalence, type-specific prevalence and extent of multiple infections were assessed in 1057 cervical samples. The Clinical Array HPV assay was used to detect 35 HPV types. According to histological diagnosis, 425 samples were normal, 375 were CIN1, and 257 were CIN2+. HPV status was studied in relation to age and lesion severity. The prevalence of HPV infection was 52.7%; 25.4%, 67.2% and 76.7% were positive for any HPV type in the normal, CIN1 and CIN2+ cases, respectively. Among HPV-positive cases, 32.0% were associated with multiple infections. Among multiple infections, 96.1% harboured HR HPV types and 38.2% HR-low risk (LR) HPV types. Overall, 33 different HPV types (18 HR and 15 LR) were detected. HR HPV types (44.1%) were significantly more prevalent than LR HPV types (8.6%). The most frequent genotype was HPV 16 (25.5%), followed by HPV 31, 53, 66, 58, and 51. Multiple infections showed a significant increase (p 0.005) according to severity of neoplasia, particularly for HR-HR HPV infections (p 0.003). No association between age and multiple HPV infections was observed (p 0.812). However, multiple HR HPV infections were more frequent in women under 30 years of age (35.3%). Fundação Calouste Gulbenkian (Ref. 96507) e Comissão de Fomento de Investigação em Cuidados de Saúde (Ref. 13374)

[PT] Introdução/Objetivos: A infeção persistente pelo Vírus do Papiloma Humano de alto risco (HPVar) é considerada como a causa necessária, embora não suficiente, para o desenvolvimento do cancro do colo do útero, sugerindo que outros fatores estarão envolvidos no processo de carcinogénese. Este estudo pretendeu avaliar indicadores de prognóstico da persistência da infeção por HPV, nomeadamente o estado físico e a carga viral dos HPV 16 e 18 e a superexpressão dos transcritos do RNAm dos HPV 16, 18, 31, 33 e 45, num grupo de mulheres com ou sem sintomatologia clínica e citopatológica. Material e Métodos: Foram estudadas 378 alíquotas de células epiteliais congeladas pertencentes a utentes dos centros de saúde do Serviço Nacional de Saúde e de clínicas privadas, referenciadas para teste HPV, entre Janeiro de 2007 e Dezembro de 2010. De acordo com o diagnóstico citopatológico, foram definidos cinco grupos: normal, ASCUS, LSIL, HSIL e carcinoma invasivo do colo do útero. Para a determinação do estado físico do DNA e da carga viral dos HPV 16 e 18 foi utilizada metodologia de PCR em tempo real, e para a superexpressão dos transcritos dos oncogenes E6 e E7 o sistema comercial NucliSENS EasyQ HPV. Os indicadores foram analisados em associação com os tipos de lesão do colo do útero. Para a análise estatística foi utilizado o o programa informático SPSS versão 16.0 e o teste de Chi-Quadrado. Resultados: Os resultados mostraram ausência de associação estatisticamente significativa entre a gravidade da lesão e o estado físico do DNA dos HPV 16 e 18. A superexpressão dos transcritos do RNAm E6/E7 e a carga viral dos HPV 16 e 18 aumentaram significativamente em função do grau da lesão. Conclusões: Os resultados obtidos sugerem que a determinação do estado físico do DNA dos HPV 16 e 18, isoladamente, não constitui um indicador de prognóstico para o desenvolvimento e progressão das lesões. A superexpressão dos transcritos dos oncogenes E6 e E7 está associada à progressão das lesões do colo do útero e apresenta maior especificidade no diagnóstico precoce das lesões pré-malignas. A quantificação do DNA dos HPVar pode ser um indicador promissor de prognóstico das lesões pré-neoplásicas do colo do útero. [ENG] INTRODUCTION/OBJECTIVE: Persistent infection with high-risk human papillomavirus (HPV) types is a necessary cause for cervical cancer development. The aim of this study was to evaluate the significance of different molecular markers for cervical carcinogenesis, and to assess their association with cervical intraepithelial neoplasia. MATERIALS AND METHODS: 378 cervical samples from women attending to primary Health Clinics of the National Health Service and Gynaecological Outpatient Clinics and referred for HPV testing were analyzed between between January 2007 and December 2010. According to cytological diagnosis, five groups were defined: normal, ASCUS, LSIL, HSIL, and ICC. For the determination of viral DNA physical status was performed by using a real-time PCR methodology, over expression of E6/E7 mRNA NASBA amplification was performed with the NucliSENS EasyQ HPV assay and viral load was determined by a real-time PCR. HPV status was studied in relation to lesion severity. Statistical analysis was performed with SPSS software 16.0 and Chi-Square test. RESULTS: No significant statistical differences were found between the physical status of HPV 16 or 18 and lesion severity. Overexpression of E6/E7 mRNA increased with lesion severity. Viral load was significantly associated with the development of cervical intraepithelial lesion. CONCLUSIONS: Data suggests that viral integration for HPV 16 seems to be an early event on cervical carcinogenesis, not being suitable as a molecular marker. E6/E7 mRNA and viral load can be more valuable approaches to use as biomarkers in the prevention of cervical cancer development. Fundação Calouste Gulbenkian (Ref. 96507) e da Comissão de Fomento de Investigação em Cuidados de Saúde (Ref. 13374).

Persistent infection by high-risk human papillomavirus (HR-HPV) is a cause of cervical cancer. The use of HPV detection in cervical screening programs may improve the ability to identify women at risk of cervical cancer. Therefore, the development of appropriate methods for the detection of HR-HPV is essential. The aim of this study was to evaluate the clinical performance of the CLART Human Papillomavirus 2 assay (CLART) in comparison with the Hybrid Capture 2 test (HC2), using a clinical cut-off of cervical intraepithelial neoplasia grade 2 or worse. Discrepant results were analyzed further by the PapilloCheck HPV genotyping system. In the 425 studied women, HR-HPV positivity rates were similar by both tests (CLART-13 HR-HPV: 63.1%; CLART-17 HR-HPV: 64.7%; HC2: 64.5%). Agreement between CLART-13 HR-HPV (k¼ 0.969; concordance level 98.6%), CLART-17 HR-HPV (k¼ 0.974; concordance level 98.8%), and HC2 were very good. When 13 HR-HPV types were considered, the two tests showed a clinical sensitivity of 96% (95% CI: 92.6–97.9). The clinical specificity of CLART-13 HR-HPV was 73.6% (95% CI: 66.7–79.5) for cervical intraepithelial neoplasia grade 2 or worse, which was comparable to HC2 (71.4%; 95% CI: 64.3–77.5). When all 17 HR-HPV types were considered, CLART showed a clinical sensitivity of 96.9% (95% CI: 93.8–98.5) and a clinical specificity of 71.9% (95% CI: 64.9–78.0). In conclusion, the CLART assay is efficient, sensitive, reproducible, and has a similar performance to HC2 for cervical intraepithelial neoplasia grade 2 or worse. Furthermore, this assay has the advantage of detecting and genotyping 35 HPV types by a single test, which can provide additional information on the predictive value of infection with HR-HPV Grant sponsor: Fundação Calouste Gulbenkian; Grant number: 96507; Grant sponsor: Comissão de Fomento de Investigação em Cuidados de Saúde; Grant number: 13374.

Persistent high-risk human papillomavirus (HPV) infection is considered as the central cause of invasive cervical cancer. Specific HPV 16 and 18 sequence variations were associated with an increased risk for progression. The purpose of this study was to analyze intratypic variations of HPV 16 and 18 within the E6 gene, MY09/11 and LCR regions, and to evaluate the risk of these variants for cervical neoplasia among Portuguese women. Cervical samples from 187 HPV 16-positive and 41 HPV 18-positive women with normal epithelium, cervical intraepithelial neoplasia, or invasive cervical cancer were amplified by type-specific PCR, followed by sequence and phylogenetic analysis. Sixteen new HPV 16 and 18 patterns are described in this paper. European HPV 16 variants were the most frequent (74.3%), particularly Ep-T350 (44.4%), followed by African (16.1%), and Asian-American (9.6%). Non- European HPV 16 variants were more frequent in pre-invasive lesions than in normal tissue and low-grade lesions. However, when analyzed separately, only African variants were associated significantly with an increased risk for cervical cancer. For HPV 18, the AsAi variant showed a trend, which was not statistically significant to an enhanced oncogenicity. European variants seemed to be significantly associated with a lower risk for cervical cancer development. The distribution of HPV 16 and 18 variants was not related to age or race among women living in the same geographical region. Knowledge of variants will be important for risk determination as well as for designing primers or probes for HPV detection methods, and for appropriate cervical cancer prevention strategies. Instituto Nacional de Saúde Doutor Ricardo Jorge, Fundação Calouste Gulbenkian (Ref. 68762)

Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis worldwide. In Portugal, due to improvements in sanitation epidemic outbreaks of HAV infection have become less frequent. This report is the first, to our knowledge that characterized HAV in Portugal. For the detection and molecular characterization of HAV cases in a group of Portuguese individuals in the Lisbon area, 31 serum samples were tested: 8 from symptomatic children from an acute hepatitis A outbreak in a Roma (Gipsies) community (2004–2005), and 22 from patients with acute HAV from sporadic cases (2005–2006). A sample of CSF involved in a case of meningitis was also included. IgM anti-HAV detection and nested reverse transcription (RT-PCR), with primers located at the VP1-P2a region, was undertaken to detect HAV genome. In positive samples, molecular characterization was followed by phylogenetic analysis. All samples (n = 31) were positive for IgM anti-HAV. HAV RNA was found in 96.7% of cases. All isolates were classified as genotype I: 22 belonged to sub-genotype IA (73.3%), and 8 to sub-genotype IB (26.7%). All strains obtained from an acute HAV outbreak had sub-genotype IA, in which seven isolates (87.5%) had identical sequences. In HAV sporadic cases sub-genotypes IA and IB were identified, and this may reflect the co-circulation of these two sub-genotypes in Portugal. Molecular epidemiology of HAV infection in this group of Portuguese appears to be similar to other European countries. HAV phylogenetic studies can provide important information for the design of appropriate public health measures. J. Med. Virol. 79:483–487, 2007. © 2007 Wiley-Liss, Inc.