Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer.

Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73-0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (rs = 0.46, p < 0.01) compared to the conventional method (rs = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.

Validity of a Minimally Invasive Autopsy for Cause of Death Determination in Adults in Mozambique: An Observational Study.

BACKGROUND: There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique. METHODS AND FINDINGS: In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation. CONCLUSIONS: A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality.

Validity of a Minimally Invasive Autopsy for Cause of Death Determination in Adults in Mozambique: An Observational Study

There is an urgent need to identify tools able to provide reliable information on the cause of death in low-income regions, since current methods (verbal autopsy, clinical records, and complete autopsies) are either inaccurate, not feasible, or poorly accepted. We aimed to compare the performance of a standardized minimally invasive autopsy (MIA) approach with that of the gold standard, the complete diagnostic autopsy (CDA), in a series of adults who died at Maputo Central Hospital in Mozambique. Methods and findings: In this observational study, coupled MIAs and CDAs were performed in 112 deceased patients. The MIA analyses were done blindly, without knowledge of the clinical data or the results of the CDA. We compared the MIA diagnosis with the CDA diagnosis of cause of death. CDA diagnoses comprised infectious diseases (80; 71.4%), malignant tumors (16; 14.3%), and other diseases, including non-infectious cardiovascular, gastrointestinal, kidney, and lung diseases (16; 14.3%). A MIA diagnosis was obtained in 100/112 (89.2%) cases. The overall concordance between the MIA diagnosis and CDA diagnosis was 75.9% (85/112). The concordance was higher for infectious diseases and malignant tumors (63/80 [78.8%] and 13/16 [81.3%], respectively) than for other diseases (9/16; 56.2%). The specific microorganisms causing death were identified in the MIA in 62/74 (83.8%) of the infectious disease deaths with a recognized cause. The main limitation of the analysis is that both the MIA and the CDA include some degree of expert subjective interpretation. Conclusions: A simple MIA procedure can identify the cause of death in many adult deaths in Mozambique. This tool could have a major role in improving the understanding and surveillance of causes of death in areas where infectious diseases are a common cause of mortality

Spinous Process Osteochondroma as a Rare Cause of Lumbar Pain.

We present a case of a 5th Lumbar Vertebra (L5) spinous process osteochondroma as a rare cause of lumbar pain in an old patient. A 70-year-old male presented with progressive and disabling lower lumbar pain. Tenderness over the central and left paraspinal area of the lower lumbar region and a palpable mass were evident. CT scan showed a mass arising from the spinous process of L5. Marginal resection of the tumor was performed through a posterior approach. The histological study revealed an osteochondroma. After surgery, pain was completely relieved. After one year there was no evidence of local recurrence or symptoms. Osteochondromas rarely involve the spine, but when they do symptoms like pain, radiculopathy/myelopathy, or cosmetic deformity may occur. The imagiologic exam of election for diagnosis is CT scan. When symptomatic the treatment of choice is surgical resection. The most concerning complication of osteochondromas is malignant transformation, a rare event.

Carriage prevalence of Salmonella enterica serotype Typhi in gallbladders of adult autopsy cases from Mozambique.

INTRODUCTION: Typhoid fever is an important public health problem in many low-income countries where asymptomatic carriers play an important role in its dissemination. The bacterium causing typhoid fever can live in the gallstones of asymptomatic persons after the infection. These carriers are reservoirs of S. Typhi, are highly contagious, and spread the disease through the secretion of bacteria in feces and urine. The aim of this study was to determine the carrier rate in an area of Mozambique. METHODOLOGY: The presence of S. Typhi was analyzed in gallbladder samples obtained from 99 adult corpses (in-hospital deaths) from Mozambique by gold-standard culture and polymerase chain reaction (PCR). RESULTS: Only one sample was positive with the culture. However, nine additional samples were positive by PCR and confirmed by DNA sequencing. Thus, the prevalence of S. Typhi was 10.1% (10/99). CONCLUSIONS: We report a high prevalence of S. Typhi in gallbladders among adult autopsy cases from Mozambique.

The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues.

The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3-99.7) and a specificity of 95.7% (95% CI: 78.1-99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis.

Infectious cause of death determination using minimally invasive autopsies in developing countries.

In developing countries, the knowledge of the microorganisms causing fatal infections is critical and could help designing and implementing more effective preventive interventions and treatment guidelines. We aimed to develop and validate protocols for microbiological analysis in post-mortem samples obtained during minimally invasive autopsy (MIA) procedures and to assess their performance. Thirty MIAs performed in adults at Maputo Central Hospital in Southern Mozambique were included in the analysis. Microbiological tests included a universal screening for HIV, hepatitis B and C viruses, Plasmodium falciparum, and bacterial/fungal culture. In addition, a variety of molecular microbiology assays guided by the histological results were performed in blood, cerebrospinal fluid and a variety of tissue samples including liver, lung and central nervous system. The combination of culture-based methods together with molecular microbiological assays led to the identification of 17 out of 19 (89.5%) of the infectious deaths. Microorganisms identified included Mycobacterium tuberculosis, Toxoplasma gondii, Pneumocystis jiroveci, Cryptococcus neoformans, hepatitis B virus, human herpesvirus 8, cytomegalovirus, Streptococcus pneumoniae, Streptococcus dysgalactiae, Ryzopus oryzae, and Acinetobacter baumannii. The combination of classical cultures, serological tests and molecular assays performed in samples obtained through MIA allows the identification of most infectious agents causing death.

Pathological Methods Applied to the Investigation of Causes of Death in Developing Countries: Minimally Invasive Autopsy Approach.

BACKGROUND AND AIMS: Complete diagnostic autopsies (CDA) remain the gold standard in the determination of cause of death (CoD). However, performing CDAs in developing countries is challenging due to limited facilities and human resources, and poor acceptability. We aimed to develop and test a simplified minimally invasive autopsy (MIA) procedure involving organ-directed sampling with microbiology and pathology analyses implementable by trained technicians in low- income settings. METHODS: A standardized scheme for the MIA has been developed and tested in a series of 30 autopsies performed at the Maputo Central Hospital, Mozambique. The procedure involves the collection of 20 mL of blood and cerebrospinal fluid (CSF) and puncture of liver, lungs, heart, spleen, kidneys, bone marrow and brain in all cases plus uterus in women of childbearing age, using biopsy needles. RESULTS: The sampling success ranged from 67% for the kidney to 100% for blood, CSF, lung, liver and brain. The amount of tissue obtained in the procedure varied from less than 10 mm2 for the lung, spleen and kidney, to over 35 mm2 for the liver and brain. A CoD was identified in the histological and/or the microbiological analysis in 83% of the MIAs. CONCLUSIONS: A simplified MIA technique allows obtaining adequate material from body fluids and major organs leading to accurate diagnoses. This procedure could improve the determination of CoD in developing countries.