A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.

Recent Changes in the Human Metapneumovirus Outbreak at a University Hospital in Korea.

BACKGROUND: Although the detection of respiratory viruses other than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was significantly reduced because of quarantine due to the coronavirus disease (COVID-19) pandemic, an epidemic of several viruses was reported unexpectedly. We also detected a change in the pattern of human metapneumovirus (HMPV) outbreak compared to that before the COVID-19 pandemic. Therefore, the authors intended to identify the incidence and altered distribution pattern of the HMPV outbreak and provide useful information for clinical practice. METHODS: This retrospective study investigated the incidence and distribution of HMPV from March 2020 to December 2022 during the COVID-19 pandemic. Detection of respiratory microorganisms was performed by multiplex polymerase chain reaction using a commercial kit and FilmArray assay. RESULTS: The overall incidence of at least one respiratory microorganism was 50.3% (1,152/2,290). HMPV was not detected between March 2020 and June 2022. However, it was suddenly detected in July 2022 and continued for approximately five months until November 2022. In particular, the detection rate of HMPV was high in September and October 2022, accounting for approximately 76.1% (51/67) of the total HMPV-positive cases. Seasonally, 92.5% (62/67) of HMPV cases were detected in autumn, while the rest of the cases were detected in summer. The HMPV detection rate, according to the age group, was highest in group 4 (3 - 6 years) at 7.4% (27/367), followed by group 3 (4 months to 2 years) at 3.6% (31/861). In HMPV-positive cases, the rate of more than two respiratory pathogens was 46.3% (31/67). An analysis of co-infecting pathogens showed that HMPV with rhinovirus A/B/C/ enteroviruses accounted for the highest percentage (51.6%), followed by HMPV with respiratory syncytial virus (48.4%). CONCLUSIONS: The COVID-19 pandemic has caused several changes in our lives. This study confirmed that the seasonal distribution of HMPV was different from that before the COVID-19 pandemic. Therefore, it can be assumed that the distribution of other respiratory microorganisms could have changed and it appears that changes could occur in previously known viral epidemiology. Clinicians should therefore be alert to this possibility.

Changes in the Distribution of Respiratory Microorganisms before and during the COVID-19 Pandemic, Daegu, Korea.

BACKGROUND: Acute respiratory infection (ARI) is the most common infectious disease in all ages and genders worldwide. Respiratory microorganisms such as respiratory viruses, are commonly responsible for causing ARI. COVID-19 is still prevalent in Korea. The implementation of lockdown and strict control measures, the mandatory wearing of masks, and social distancing are critical steps for controlling the risk of COVID-19 spread. This study was conducted to find out how these changes in daily lives impacted the distribution of respiratory microorganisms. METHODS: A retrospective study was conducted to identify the incidence and distribution patterns of ARI-causing respiratory microorganisms before (Period Ⅰ) and during the COVID-19 pandemic (Period Ⅱ) in terms of detection method, age, month, and season. In particular, data in Periods Ⅰ and Ⅱ were compared for eight major kinds of respiratory microorganisms: adenovirus (AdV), human metapneumovirus (HMPV), human rhinovirus/enterovirus (Rhino/Entero), influenza virus (Flu) A, Flu B, human parainfluenza virus (HPIV) 3, respiratory syncytial virus, and Mycoplasma pneumoniae. RESULTS: A total of 27,191 respiratory specimens were tested, of which 5,513 were obtained from children and adolescents (age groups 1 ⁓ 5) and 21,678 from adults (age group 6). The overall positive rates for at least one respiratory microorganism in Periods Ⅰ and Ⅱ were 23.1% (1,199/5,193) and 4.9% (1,070/21,998), respectively (p < 0.001). The overall positive rates in male and female patients were significantly different (8.7% vs. 7.9%; p = 0.016). On the FilmArray™ RP assay, positive rates in all age groups decreased significantly in Period Ⅱ compared with Period Ⅰ. AdV, Rhino/Entero, and Flu A were detected in all four seasons, but HMPV and HPIV3 were not detected. The overall positive rates on FilmArray and the Flu antigen test in Period Ⅱ were significantly decreased. In the COVID-19 test, the positive rates were high in March and April 2020, and decreased thereafter, but these increased again in the winter of 2020/2021. CONCLUSIONS: Life changes due to COVID-19 pandemic have had a significant impact on the distribution of respiratory microorganisms; our study results might provide useful information on respiratory virus epidemiology.

Review of washing machine-related deaths in South Korea.

We reviewed data on washing machine-related deaths between 2008 and 2020 in South Korea to analyze the case characteristics, manners of death, and causes of death. Washing machine-related deaths are very rare, and only 23 incidents were identified over the study period. Of these cases, 19 (82.6%) were related to general pulsator-type top load washing machines; the other 4 (17.4%) were related to front-load washing machines. The pulsator-type top load washing machine-related deaths occurred in people aged between 40 and 93 years (mean age, 68 years), including 9 men (47.4%) and 10 women (52.6%). The manners of death among the incidents were suicide in 12 cases (63.2%), accident in 6 cases (31.6%), and unknown in 1 case (5.3%). A Medline search of the English literature currently does not yield results for washing machine-related suicidal deaths in adults. Of the 12 suicide cases, 4 were autopsied; suicidal death was determined by postmortem investigation or based on suicide notes. Washing machine-related suicidal deaths are presumed to have characteristics similar to those of bathtub suicidal deaths. The front-load washing machine-related deaths involved boys aged between 6 and 8 years, and all cases were concluded as accidents. The cause of death was hypoxia resulting from the children being accidentally trapped inside the washing machine while playing. Greater attention to vulnerable groups, especially children and older adults, is required to reduce the rate of washing machine-related accidental or suicidal deaths.

Spindle cell oncocytoma of the sella turcica with anaplastic features and rapid progression in short-term follow-up: a case report with proposal of distinctive radiologic features.

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

Successful laparoscopic surgery of accessory cavitated uterine mass in young women with severe dysmenorrhea.

Accessory cavitated uterine mass (ACUM) is a rare and unique condition seen in young women. We report cases of ACUMs in two patients, a 14-year-old girl and a 25-year-old woman, both with complaints of severe dysmenorrhea that had started at menarche and had progressively worsened since. A large cystic lesion was localized in the anterolateral wall of the myometrium separate from the endometrium, which was difficult to distinguish from congenital uterine anomalies. Laparoscopic excision of the ACUMs was successful and completely resolved the dysmenorrhea. Early investigation of severe dysmenorrhea in young women can provide appropriate management and relieve symptoms.

Extramedullary tanycytic ependymoma of the lumbar spinal cord.

Tanycytic ependymoma is a rare variant of ependymoma that commonly affects the cervical and thoracic spinal cord. It usually arises as intramedullary lesions, and extramedullary cases are extremely rare. We report a case of a 44-year-old woman who was diagnosed with tanycytic ependymoma in her lumbar spine at level 2-3. The tumor mass developed in an intradural extramedullary location. Histopathologically, tanycytic ependymoma can be misdiagnosed as schwannoma or pilocytic astrocytoma. Immunohistochemical findings such as strong positivity for glial fibrillary acidic protein, perinuclear dot-like positive patterns for epithelial membrane antigen, and focal positivity for S-100 are helpful in diagnosing tanycytic ependymoma. It is important to be aware of this rare tumor to ensure appropriate patient management and accurate prognosis.

Plasma components affect accuracy of circulating cancer-related microRNA quantitation.

Circulating microRNAs (miRNAs) have emerged as candidate biomarkers of various diseases and conditions including malignancy and pregnancy. This approach requires sensitive and accurate quantitation of miRNA concentrations in body fluids. Herein we report that enzyme-based miRNA quantitation, which is currently the mainstream approach for identifying differences in miRNA abundance among samples, is skewed by endogenous serum factors that co-purify with miRNAs and anticoagulant agents used during collection. Of importance, different miRNAs were affected to varying extent among patient samples. By developing measures to overcome these interfering activities, we increased the accuracy, and improved the sensitivity of miRNA detection up to 30-fold. Overall, the present study outlines key factors that prevent accurate miRNA quantitation in body fluids and provides approaches that enable faithful quantitation of miRNA abundance in body fluids.

Upregulated amniotic fluid cytokines and chemokines in emergency cerclage with protruding membranes.

PROBLEM To identify the prognostic factors for pregnancy outcome in women who received emergency cerclage for dilated cervix with protruding membranes. METHOD OF STUDY A prospective cohort study was performed, and a total of 14 women who received emergency cerclage were included. Clinical features and laboratory findings including amniotic fluid cytokines and chemokines were compared between women who had successful pregnancy (survival group, n = 6) and those who had perinatal death (non-survival group, n = 8). Five healthy pregnant women served for normal controls for amniotic fluid study. RESULTS The overall neonatal survival was 42.9% in women with emergency cerclage. Serum C-reactive protein levels on postoperative day 3 and 7 were significantly higher in non-survival group when compared with those in survival group (P = 0.002, P = 0.01). Amniotic fluid levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemoattractant protein-1 levels of the patients were significantly higher than those of normal controls. Amniotic fluid levels of IL-1α, IL-1ß, and IL-8 were significantly increased in the non-survival group when compared with those of the survival group. CONCLUSION Systemic and local inflammatory markers including proinflammatory cytokines and chemokines may predict pregnancy outcome in women with emergency cerclage for dilated cervix with protruding membranes.

Selective release of microRNA species from normal and malignant mammary epithelial cells.

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease.

Expression and mutational analysis of c-kit in ovarian surface epithelial tumors.

Coexpression of Kit ligand and c-kit has been reported in some gynecologic tumors. To determine whether imatinib mesylate is useful in ovarian epithelial tumors, we performed immunohistochemical and mutational analysis. The cases consisted of 33 cases, which included 13 serous cystadenocarcinomas, 1 borderline serous tumor, 8 mucinous cystadenocarcinomas, 6 borderline mucinous tumors and 5 clear cell carcinomas. Five cases of serous cystadenoma and 5 cases of mucinous cystadenoma were also included. In the immunohistochemical study, 3 cases (3/6, 50%) of borderline mucinous cystic tumor and two cases (2/8, 25%) of mucinous cystadenocarcinoma show positive staining for KIT protein. Only one case (1/13, 7.7%) of serous cystadenocarcinoma had positive staining. On mutational analysis, no mutation was identified at exon 11. However, two cases of borderline mucinous tumors and one case of mucinous cystadenocarcinoma had mutations at exon 17. In these cases, the immunohistochemistry also shows focal positive staining at epithelial component. Although, KIT protein expression showed higher incidence in mucinous tumors than serous tumors, they lack KIT-activating mutations in exon 11. Thus, ovarian surface epithelial tumors are unlikely to respond to imatinib mesylate.

The role of microsatellite instability at chromosome 11p15.5 in the progression of breast ductal carcinoma.

The study of microsatellite instability (MSI) has provided the evidence to support a sequential, progressive pathway for the development of cancer. In this study, we analyzed the role of MSI at chromosome 11p15.5 using microdissection of paraffin-embedded tissue from 68 matched normal and breast tumor samples. Components of intraductal, invasive and metastatic foci in lymph node were assessed for MSI using the polymorphic markers D11S922, tyrosine hydroxylase (TH) and D11S988. We found that MSI at D11S922 was relatively high incidence than other two markers and increased during breast cancer progression. The overall frequency of MSI at D11S922 was 26.7% in pure intraductal carcinoma, 36.4% in invasive carcinoma, and 40.0% in invasive carcinoma with metastases. We observed no significant correlation between MSI at chromosome 11p15.5 and the patient's age, tumor size, histological grade, or lymph node metastasis. We compared the MSI incidence with the expression of prognostic markers, such as p53, c-erb B2, estrogen receptor, and progesterone receptor, and found no significant correlation. We suggest that the MSI of chromosome 11p15.5 is increased during breast cancer progression, but long-term follow-up study would establish whether MSI at chromosome 11p15.5 could be useful as a potential prognostic marker for breast cancer.