Development of a predictive score to discriminate community acquired pneumonia with underlying lung cancer: A retrospective case - control study.

BACKGROUND: A pneumonic infiltrate might hide an occult lung cancer (LC). This awareness depends on each clinician personal experience, turning definitive LC diagnosis challenging and possibly delayed. In this study we aimed to develop a clinical score to better identify those cases. MATERIALS AND METHODS: We conducted a retrospective case-control study, including previously undiagnosed LC patients admitted in our institution, with a presumptive suspicious of community acquired pneumonia (CAP). Cases were compared with random CAP inpatient controls, using a matched 2:1 ratio. Demographic, clinical, and laboratorial variables were assessed for a possible association with the presence of a CAP with underlying LC (CAP-uLC). RESULTS: Among 535 hospitalized LC patients, 43 cases had a presentation compatible with CAP and were compared with 86 CAP controls. A scoring system was built using 6 independent variables, which positively correlated with CAP-uLC: smoking history (OR: 8.3 [1.9-36.2]; p = 0.005); absence of fever (6.5 [2.0-21.5]; p = 0.002); sputum with blood (5.9 [1.2-29.9]; p = 0.033); platelet count ≥ 232x103/µL (5.8 [1.6-20.6]; p = 0.006); putative alternative diagnosis than CAP (4.6 [1.5-14.7]; p = 0.009); and duration of symptoms ≥ 10 days (3.7 [1.1-13.0]; p = 0.037). Our score presented an AUC of 0.910 (95 % CI, 0.852-0.967; p < 0.001), a sensitivity of 88.1 % and specificity of 84.7 %, in predicting the risk of presenting a CAP-uLC, when set to a cutoff of 18. CONCLUSION: We propose a novel risk score aimed to aid clinicians identifying patients with CAP-uLC in the acute setting, possibly prompting early LC diagnosis.

Unusual Urologic Metastasis From Gastrointestinal Cancers: A Compilation of Case Reports and Literature Review.

Gastrointestinal cancers are highly prevalent around the world. In the metastatic setting, the most usual sites for metastases are the liver, lymph nodes, peritoneum, and lung. Urologic metastases are very rare. We report a case series of three patients with gastrointestinal tumours in different topographies (stomach, colon, and rectum) with urological metastases. In all cases, the patients were initially treated with curative intent. Two of the patients presented with bladder metastases, and the third had penile metastases in addition to pulmonary metastases. Haematuria was the most common symptom at presentation. One of the patients had a good overall survival and is still undergoing palliative intent chemotherapy. In the literature, there are few reported cases of urological metastases from gastrointestinal cancers, and that is the aim of this publication.

Clostridium difficile Severity and Outcome at a North of Portugal Healthcare Facility.

INTRODUCTION: Clostridium difficile infection has been increasingly reported, with a significant healthcare burden and important morbimortality. This study aimed to characterize and describe the severity and outcomes of this event at a Portuguese hospital. MATERIAL AND METHODS: We conducted a retrospective analysis, by clinical record review, of all confirmed cases diagnosed in a hospital in the North of Portugal, between January 2013 and December 2018. We included those who were non-pregnant and at least 18 years old. RESULTS: Fifty-seven cases occurred, mostly in females and aged patients; 33.3% were healthcare facility-outset, while 31.6% were community-associated. Regarding severity, 43.9% had non-severe, while 29.8% severe and 21.0% fulminant presentations, the latter with the need of admission. Exposure to antibiotics occurred in 68.4%, while to proton-pump inhibitors in 57.9%. Risk factors for severe disease were female gender, chronic renal disease, and high neutrophil-lymphocyte ratio. Moreover, renal disease and a higher ratio were associated with fulminant disease. Thirty-day all-cause mortality was found in 15.8% while 90-day in 28.1%. Risk factors for 30-day mortality were renal disease, higher Charlson score, and higher neutrophil-lymphocyte ratio. Risk factors for 90-day mortality were advanced age, previous antibiotic exposure, higher Charlson score, and higher neutrophil-lymphocyte ratio. CONCLUSION: Data concerning Clostridium difficile infection severity and prognosis in Portugal is scarce, and future studies should focus on this important topic.

Introdução: A infeção por Clostridium difficile tem aumentado, com importante morbimortalidade e impacto nos sistemas de saúde. Este estudo procurou caracterizar e descrever a severidade e prognóstico desta infeção, na nossa instituição. Material e Métodos: Realizou-se uma análise retrospetiva dos casos confirmados ocorridos entre janeiro de 2013 e dezembro de 2018, num hospital do Norte de Portugal. Recorreu-se à análise de processo clínico e foram incluídos doentes sem gravidez em curso e com pelo menos 18 anos. Resultados: Verificaram-se 57 casos, a maioria em mulheres e idosos, sendo que 33,3% tiveram origem em instituições de saúde e 31,6% na comunidade. Nesta amostra, 43,9% tiveram doença não severa, 29,8% severa e 21,0% fulminante, estes com necessidade de internamento. A toma prévia de antibióticos ocorreu em 68,4%, e de inibidores da bomba de protões em 57,9%. O sexo feminino relacionou-se com doença severa, enquanto que a doença renal crónica e um elevado rácio neutrófilos-linfócitos se relacionaram com doença severa e fulminante. A mortalidade aos 30 dias verificou-se em 15,8% e associou-se a doença renal e elevação do score de Charlson e do rácio neutrófilos-linfócitos. A mortalidade aos 90 dias ocorreu em 28,1%, associada a idade avançada, toma de antibióticos e elevação do score e do rácio. Conclusão: Em Portugal, são escassos os dados sobre a severidade e prognóstico desta infeção, pelo que são necessários mais estudos nacionais.

High resolution melting analysis of KRAS, BRAF and PIK3CA in KRAS exon 2 wild-type metastatic colorectal cancer.

BACKGROUND: KRAS is an EGFR effector in the RAS/RAF/ERK cascade that is mutated in about 40% of metastatic colorectal cancer (mCRC). Activating mutations in codons 12 and 13 of the KRAS gene are the only established negative predictors of response to anti-EGFR therapy and patients whose tumors harbor such mutations are not candidates for therapy. However, 40 to 60% of wild-type cases do not respond to anti-EGFR therapy, suggesting the involvement of other genes that act downstream of EGFR in the RAS-RAF-MAPK and PI3K-AKT pathways or activating KRAS mutations at other locations of the gene. METHODS: DNA was obtained from a consecutive series of 201 mCRC cases (FFPE tissue), wild-type for KRAS exon 2 (codons 12 and 13). Mutational analysis of KRAS (exons 3 and 4), BRAF (exons 11 and 15), and PIK3CA (exons 9 and 20) was performed by high resolution melting (HRM) and positive cases were then sequenced. RESULTS: One mutation was present in 23.4% (47/201) of the cases and 3.0% additional cases (6/201) had two concomitant mutations. A total of 53 cases showed 59 mutations, with the following distribution: 44.1% (26/59) in KRAS (13 in exon 3 and 13 in exon 4), 18.6% (11/59) in BRAF (two in exon 11 and nine in exon 15) and 37.3% (22/59) in PIK3CA (16 in exon 9 and six in exon 20). In total, 26.4% (53/201) of the cases had at least one mutation and the remaining 73.6% (148/201) were wild-type for all regions studied. Five of the mutations we report, four in KRAS and one in BRAF, have not previously been described in CRC. BRAF and PIK3CA mutations were more frequent in the colon than in the sigmoid or rectum: 20.8% vs. 1.6% vs. 0.0% (P=0.000) for BRAF and 23.4% vs. 12.1% vs. 5.4% (P=0.011) for PIK3CA mutations. CONCLUSIONS: About one fourth of mCRC cases wild-type for KRAS codons 12 and 13 present other mutations either in KRAS, BRAF, or PIK3CA, many of which may explain the lack of response to anti-EGFR therapy observed in a significant proportion of these patients.

Comparison of methodologies for KRAS mutation detection in metastatic colorectal cancer.

Cetuximab and panitumumab are two monoclonal antibodies targeting the epidermal growth factor receptor that have been approved for treatment of metastatic colorectal cancer. Recent clinical trials found an association between KRAS mutation status and resistance to anti-epidermal growth factor receptor therapy, leading to the recommendation to perform KRAS mutation analysis before cetuximab or panitumumab treatment. This study was designed to compare and evaluate the efficacy of four different methodologies--high resolution melting, Sanger sequencing, DxS kit, and SNaPshot--for KRAS mutation detection in a clinical setting. In total, 372 samples from patients with metastatic colorectal cancer were analyzed by high resolution melting and SNaPshot, with 184 of those being further analyzed by Sanger sequencing and 188 with the DxS kit. Sensitivities were compared after consensus findings were determined by the presence of the same result in two of the three methodologies used in each case. The frequency of KRAS codon 12 and 13 mutations in our population was 43.5%, and a discordant finding was observed in 22 samples. Comparing to Sanger sequencing, significantly more consensus mutations were detected by the DxS kit (P=0.0139), high resolution melting (P=0.0004), and SNaPshot (P=0.00001), but no statistically significant differences were found among the three methodologies with higher sensitivity.

Análise microbiológica de carne de frango crua, após o processo de moagem / Microbiological analysis of raw chicken meat after the milling process

As exigências pela qualidade da carne estão cada vez maiores, tanto no mercado internacional quanto no nacional. O consumidor está mais ciente dos atributos de qualidade microbiológica da carne de frango após o processo de moagem, em um estabelecimento com comercialização no varejo (supermercado) da cidade de Cascavel, Paraná. Foram coletadas quatro amostras, sendo elas: amostra 1 – carne de frango moída no momento da coleta; amostra 2 – carne de frango moída e acondicionada em bandeja de isopor; amostra 3 – carne de frango moída e acondicionada em embalagem filme e amostra 4 – carne de frango moída e acondicionada em saco plástico. Determinou-se a quantidade de mesófilos, Salmonella spp, coliformes totais e fecais de acordo com metodologias específicas para cada micro-organismo. Obteve-se contaminação das amostras analisadas: 100% mesófilos, sendo que em duas amostras (50%) o resultado obtido foi superior a 10-6 como referido por Bourgeois; 50% Salmonella spp; 100% coliformes totais e 100% de coliformes fecais em diferentes níveis. Na maioria das amostras foi constatado a presença significativa de micro-organismos patogênicos ou indicadores de manipulação inadequada nas carnes, estes sendo possíveis devido à manipulação excessiva, aumento da superfície de contato e falta de higiene do local e dos manipuladores. Com isso sugere-se a realização freqüente de treinamentos para implementar as Boas Práticas de Fabricação (BPF) com o intuito de controlar as doenças vinculadas por alimentos.

Hereditary gastrointestinal stromal tumors sharing the KIT Exon 17 germline mutation p.Asp820Tyr develop through different cytogenetic progression pathways.

Hereditary gastrointestinal stromal tumor (GIST) syndrome is a rare autosomal dominant genetic disorder originated by germline mutations in the KIT or PDGFRA genes. We report the third family with hereditary predisposition to GIST due to the KIT Exon 17 germline mutation p.Asp820Tyr and characterize the cytogenetic progression pathways followed by different GIST sharing the same primary genetic event, using a combination of chromosome banding, comparative genomic hybridization (CGH), and fluorescence in situ hybridization (FISH) analyses. The missense mutation p.Asp820Tyr was detected in the proband's rectal and gastric GIST, as well as in his aunt's GIST epiplon metastasis. The mutation p.Asp820Tyr was subsequently also found in the proband's peripheral blood DNA, as well as in that of 4 of 10 relatives thus far analyzed. CGH analysis revealed loss of 14q and 15q in the proband's gastric lesion, whereas FISH analysis of the proband's rectal GIST did not detect loss of 14q and 15q, but instead loss of 4q and 22q and gain of 20q, indicating that the two tumors were independent GIST. Chromosome banding and CGH analyses of the aunt's GIST epiplon metastasis revealed multiple cytogenetic alterations, including 1p loss, but none in common with the two proband's GIST. We conclude that, although the patients share the same KIT Exon 17 germline mutation, the multiple GIST analyzed followed different pathogenetic progression pathways, each of which did not significantly differ from what has been described in sporadic GIST.