Postmortem Findings Associated With SARS-CoV-2: Systematic Review and Meta-analysis.

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome-associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.

HMGA2, but not HMGA1, is overexpressed in human larynx carcinomas.

AIMS: Malignant tumours from the upper aerodigestive tract are grouped collectively in the class of head and neck squamous cell carcinoma (HNSCC). The head and neck tumours were responsible for more than 500 000 cancer cases in 2012, accounting for the sixth highest incidence rate and mortality worldwide among all tumour types. Laryngeal squamous cell carcinoma (LSCC) possesses the second highest incidence rate among all HNSCC. Despite significant advances in surgery and radiotherapy during the last few decades, no treatment has been shown to achieve a satisfactory therapeutic outcome and the mortality rate of LSCC is still high, with a 5-year survival rate of 64%. Therefore, further investigations are required to identify the pathogenesis of LSCC. METHODS AND RESULTS: In order to search for new LSCC biomarkers, we have analysed the expression of the HMGA family members, HMGA1 and HMGA2, by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. HMGA proteins are usually absent in the healthy adult tissues. In contrast, their constitutive expression is a feature of several neoplasias, being associated with a highly malignant phenotype and reduced survival. Here, we report HMGA2 overexpression in larynx carcinomas. Conversely, HMGA1 does not show any differences in its expression between normal and carcinoma tissues. Interestingly, HMGA2 overexpression appears associated with that of two HMGA1-pseudogenes, HMGA1P6 and HMGA1P7, acting as a sponge for HMGA1- and HMGA2-targeting microRNAs and involved in several human cancers. CONCLUSIONS: Therefore, HMGA2 overexpression appears to be a strong feature of larynx carcinoma, supporting its detection as a valid tool for the diagnosis of these malignancies.

Anterior prostate biopsy at initial and repeat evaluation: is it useful to detect significant prostate cancer?

PURPOSE: Detection rate for anterior prostate cancer (PCa) in men who underwent initial and repeat biopsy has been prospectively evaluated. MATERIALS AND METHODS: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years) underwent initial (285 cases) and repeat (115 cases) prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤ 25% and ≤ 20%, respectively. A median of 22 (initial biopsy) and 31 cores (repeat biopsy) were transperineally performed including 4 cores of the anterior zone (AZ) and 4 cores of the AZ plus 2 cores of the transition zone (TZ), respectively. RESULTS: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45%) patients: in 135 (47.4%) and 45 (36%) of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy) vs 13.3% (repeat biopsy) of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5%) and 5 (71.5%) men who underwent initial and repeat biopsy, respectively. CONCLUSIONS: However AZ biopsies increased detection rate for PCa (10% of the cases), the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases).

Anterior prostate biopsy at initial and repeat evaluation: is it useful to detect significant prostate cancer?

ABSTRACT Purpose: Detection rate for anterior prostate cancer (PCa) in men who underwent initial and repeat biopsy has been prospectively evaluated. Materials and Methods: From January 2013 to March 2014, 400 patients all of Caucasian origin (median age 63.5 years) underwent initial (285 cases) and repeat (115 cases) prostate biopsy; all the men had negative digital rectal examination and the indications to biopsy were: PSA values > 10 ng/mL, PSA between 4.1-10 or 2.6-4 ng/mL with free/total PSA≤25% and ≤20%, respectively. A median of 22 (initial biopsy) and 31 cores (repeat biopsy) were transperineally performed including 4 cores of the anterior zone (AZ) and 4 cores of the AZ plus 2 cores of the transition zone (TZ), respectively. Results: Median PSA was 7.9 ng/mL; overall, a PCa was found in 180 (45%) patients: in 135 (47.4%) and 45 (36%) of the men who underwent initial and repeat biopsy, respectively. An exclusive PCa of the anterior zone was found in the 8.9 (initial biopsy) vs 13.3% (repeat biopsy) of the men: a single microfocus of cancer was found in the 61.2% of the cases; moreover, in 7 out 18 AZ PCa the biopsy histology was predictive of significant cancer in 2 (28.5%) and 5 (71.5%) men who underwent initial and repeat biopsy, respectively. Conclusions: However AZ biopsies increased detection rate for PCa (10% of the cases), the majority of AZ PCa with histological findings predictive of clinically significant cancer were found at repeat biopsy (about 70% of the cases).

PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIAL AND METHODS: From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20 %, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1 %): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50 %, 90.6 vs 71.9 %, 27.9 vs 41.8 %, 31.9 vs 31.5 % and 88.9 vs 80 %, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1 % of biopsies while missing 9.4 % and 28 % diagnosis of PCa.

PCA3 score and prostate cancer diagnosis at repeated saturation biopsy. Which cut-off: 20 or 35?

PURPOSE: To compare PCA3 score cut-off of 35 vs 20 in PCa diagnosis in patients undergoing repeated saturation prostate biopsy (SPBx). MATERIALS AND METHODS: From January 2010 to May 2011, 118 patients (median 62.5 years) with primary negative extended biopsy underwent a transperineal SPBx (median 30 cores) for persistent suspicion of PCa. The indications for repeated biopsy were: persistently high or increasing PSA values; PSA > 10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA ≤ 25% and ≤ 20%, respectively; moreover, before performing SPBx urinary PCA3 score was evaluated. RESULTS: All patients had negative DRE and median PSA was 8.5 ng/mL (range: 3.7-24 ng/mL). A T1c PCa was found in 32 patients (27.1%): PCA3 score was 59 (median; range: 7-201) in the presence of PCa and 35 (median; range: 3-253) in the absence of cancer (p < 0.05). In the presence of ASAP and HGPIN median PCA3 score was 109 (range: 42-253) and 40 (range: 30-140), respectively. Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs 35 in PCa diagnosis were 44.9 vs 50%, 90.6 vs 71.9%, 27.9 vs 41.8%, 31.9 vs 31.5% and 88.9 vs 80%, respectively. ROC analysis demonstrated an AUC for PCA3 ≥ 20 vs ≥ 35 of 0.678 and 0.634, respectively. CONCLUSIONS: Our data suggest that PCA3 is more useful as an exclusion tool; moreover, setting a PCA3 cut-off at 20 vs 35, would have avoided 22.9 vs 38.1% of biopsies while missing 9.4% and 28% diagnosis of PCa.