Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant cancer predisposition syndrome. HLRCC is characterized by the development of cutaneous leiomyomas, early-onset uterine leiomyomas, and HLRCC-associated renal cell cancer (RCC) and caused by germline fumarate hydratase (FH) deficiency. We investigated the genotypic and phenotypic characteristics of Korean patients with HLRCC. Methods: We performed direct sequencing analysis of FH in 13 patients with suspected HLRCC and their family members. A chromosomal microarray test was performed in female patients with negative sequencing results but highly suspected HLRCC. In addition, we analyzed the clinical characteristics and evaluated the genotype–phenotype correlations in Korean patients with HLRCC. Results: We identified six different pathogenic or likely pathogenic FH variants in six of the 13 patients (46.2%). The variants included two nonsense variants, two splicing variants, one frameshift variant, and one missense variant. Of the six variants, two (33.3%) were novel (c.132+1G > C, and c.243dup). RCC and early-onset uterine leiomyoma were frequently observed in families with HLRCC, while cutaneous leiomyoma was less common. No significant genotype–phenotype correlation was observed. Conclusions We describe the genotypic and phenotypic spectrum in a small series of Korean patients with HLRCC. Our data reveal the unique characteristics of Korean patients with HLRCC and suggest a need for establishing an optimal diagnostic approach for them.

No abstract available.
Hemostasis*

The 2016 WHO diagnostic criteria for chronic myelomonocytic leukemia (CMML) require both absolute and relative monocytosis (≥1×10⁹/L and ≥10% of white blood cell counts) in peripheral blood. Moreover, myeloproliferative neoplasm (MPN) features in bone marrow and/or MPN-associated mutations tend to support MPN with monocytosis rather than CMML. We assessed the impact of the 2016 WHO criteria on CMML diagnosis, compared with the 2008 WHO criteria, through a retrospective review of the medical records of 38 CMML patients diagnosed according to the 2008 WHO classification. Application of the 2016 WHO criteria resulted in the exclusion of three (8%) patients who did not fulfill the relative monocytosis criterion and eight (21%) patients with an MPN-associated mutation. These 11 patients formed the 2016 WHO others group; the remaining 27 formed the 2016 WHO CMML group. The significant difference in the platelet count and monocyte percentage between the two groups indicated that the 2016 WHO criteria lead to a more homogenous and improved definition of CMML compared with the 2008 WHO criteria, which may have led to over-diagnosis of CMML. More widespread use of molecular tests and more sophisticated clinical and morphological evaluations are necessary to diagnose CMML accurately.
Bone Marrow ; Classification ; Diagnosis* ; Humans ; Leukemia, Myelomonocytic, Chronic* ; Leukocytes ; Medical Records ; Monocytes ; Platelet Count ; Retrospective Studies

Salmonella (S.) Typhimurium is highly contagious, and its infection may rapidly spread within pig populations of herd. According to the survey (1,191 pigs) from 2003 to 2012, 155 pigs (13.0%) were diagnosed as salmonellosis in Jeju. Major porcine salmonellosis cases (88.4%) were concentrated in 4- to 12-week-old weaned pigs, but 6 pigs (3.9%) under 4 weeks old were also diagnosed. Based on the histopathologic examinations, ulcerative enteritis (63.9%) in the large intestine and/or paratyphoid nodules formation (57.4%) in the liver were most prevalent lesions in porcine salmonellosis. Single infection of S. Typhimurium and mixed infection with more than 2 pathogens were detected in 38 (24.5%) and 117 (75.5%) in pigs, respectively. Co-infections of Porcine reproductive and respiratory syndrome virus and Porcine circovirus type 2 were very common in porcine salmonellosis in Jeju and detected in 84 (54.2%) and 59 (38.1%) pigs, respectively. Based on the serotyping tests using 41 bacterial isolates, S. Typhimurium and S. Rissen were confirmed in 39 (95.1%) and 2 (4.9%) cases, respectively.
Circovirus ; Coinfection ; Enteritis ; Intestine, Large ; Liver ; Porcine respiratory and reproductive syndrome virus ; Prevalence* ; Salmonella ; Salmonella Infections* ; Salmonella typhimurium ; Serotyping ; Swine ; Ulcer

BACKGROUND: Cumulative blood culture data provide clinicians with important information in the selection of empiric therapy for blood stream infections. METHODS: We retrospectively analyzed blood culture data from a university hospital during the period from 2006 to 2015. Only the initial isolates of a given species for each patient were included. RESULTS: The number of blood cultures per 1,000 inpatient-days increased from 64 in 2006 to 117 in 2015. The ratio of significant pathogens to total isolates was 0.56-0.63. The most common organisms were Escherichia coli in 2006-2010 but changed to coagulase-negative staphylococci (CoNS) in 2011. The proportion of Staphylococci aureus was decreased during the study period, but Klebsiella pneumoniae was increased. Enterococci were increased, especially E. faecium, which was more frequently isolated than E. faecalis in 2015. Pseudomonas aeruginosa was decreased during the study, but Acinetobacter baumannii was increased. The prevalence of methicillin-resistant S. aureus (MRSA) changed from 62.2% to 53.9%, while vancomycin-resistant E. faecium increased to 35.8%. Extended-spectrum beta-lactamase (ESBL)-producing E. coli and K. pneumoniae increased to 25% and 34%, respectively, in 2015. Starting in 2008, three E. coli and 11 K. pneumoniae isolates were carbapenem-resistant Enterobacteriaceae (CRE), and three were carbapenemase-producing Enterobacteriaceae (CPE). The prevalence of imipenem-resistant A. baumannii rapidly increased during the study period. CONCLUSION: About 60% of all blood isolates were significant pathogens. The most common isolates changed from E. coli to CoNS in 2011. ESBL-producing E. coli and K. pneumoniae, vancomycin-resistant E. faecium, and imipenem-resistant A. baumannii were increased during the study, while the proportion of MRSA tended to decrease slightly. Of the total isolates, 14 were CRE, and 3 were CPE.
Acinetobacter baumannii ; Bacteremia ; beta-Lactamases ; Enterobacteriaceae ; Escherichia coli ; Humans ; Klebsiella pneumoniae ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Pneumonia ; Prevalence ; Pseudomonas aeruginosa ; Retrospective Studies ; Rivers

No abstract available.
Brain Abscess* ; Humans ; Lupus Erythematosus, Systemic* ; Nocardia*

BACKGROUND: Mutations in calreticulin (CALR) have been reported to be key markers in the molecular diagnosis of myeloid proliferative neoplasms. In most previous reports, CALR mutations were analyzed by using Sanger sequencing. Here, we report a new, rapid, and convenient system for screening CALR mutations without sequencing. METHODS: Eighty-three bone marrow samples were obtained from 81 patients with thrombocytosis. PCR primers were designed to detect wild-type CALR (product: 357 bp) and CALR with type 1 (product: 302 bp) and type 2 mutations (product: 272 bp) in one reaction. The results were confirmed by Sanger sequencing and compared with results from fragment analysis. RESULTS: The minimum detection limit of the screening PCR was 10 ng for type 1, 1 ng for type 2, and 0.1 ng for cases with both mutations. CALR type 1 and type 2 mutants were detected with screening PCR with a maximal analytical sensitivity of 3.2% and <0.8%, respectively. The screening PCR detected 94.1% (16/17) of mutation cases and showed concordant results with sequencing in the cases of type 1 and type 2 mutations. Sanger sequencing identified one novel mutation (c.1123_1132delinsTGC). Compared with sequencing, the screening PCR showed 94.1% sensitivity, 100.0% specificity, 100.0% positive predictive value, and 98.5% negative predictive value. Compared with fragment analysis, the screening PCR presented 88.9% sensitivity and 100.0% specificity. CONCLUSIONS: This screening PCR is a rapid, sensitive, and cost-effective method for the detection of major CALR mutations.
Adult ; Aged ; Base Sequence ; Bone Marrow/metabolism ; Calreticulin/chemistry/*genetics/metabolism ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Genotype ; Humans ; Janus Kinase 2/chemistry/genetics/metabolism ; Male ; Middle Aged ; Mutation ; Myeloproliferative Disorders/complications/*diagnosis/genetics ; Polymerase Chain Reaction ; Thrombocytosis/complications/*diagnosis

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematologic disorder characterized by complement-mediated hemolysis leading to severe complications, such as life threatening thrombosis. Eculizumab, a humanized anti-C5 monoclonal antibody, has dramatically improved outcomes of patients with PNH. Despite this new revolutionary treatment, clinical information regarding eculizumab use in pregnant women with PNH is limited. A 30-year-old female with PNH underwent acute aggravation of PNH presented with acute kidney injury (AKI) triggered by an infectious event. After the stabilization of AKI with supportive care and later continuous eculizumab use, a planned pregnancy was attempted and achieved because she and her spouse wanted to have a baby. We monitored the patient carefully throughout her pregnancy with 100 mg/day of aspirin and the maintenance of 900 mg of intravenous eculizumab every 2 weeks. She remained stable during pregnancy and a successful delivery was achieved without maternofetal complication.
Acute Kidney Injury ; Adult ; Aspirin ; Family Planning Services* ; Female ; Hemoglobinuria, Paroxysmal* ; Hemolysis ; Humans ; Pregnancy ; Pregnant Women ; Spouses ; Thrombosis

The number of massive transfusions for pediatric patients has risen owing to the increasing number of complex surgeries and trauma centers. However, as there are only a few studies on pediatric massive transfusion, adult massive transfusion protocols are used for pediatric patients in many hospitals and institutions. Although massive transfusion protocols would improve the outcomes and reduce the received blood products during transfusion, pediatric patients differ from adults in the tolerability to transfusion, incidence of coagulopathy, and mechanisms of injuries. Therefore clinical physicians have requested for a pediatric massive transfusion protocol. Herein, we reviewed pediatric massive transfusion protocols that have been used in various clinical settings. To date, only a few single-center studies with a small number of pediatric patients have been performed. Even though these studies did not show improvement in outcomes such as mortality and side effects, they reported a short preparation time for fresh frozen plasma products and a low coagulopathy rate in pediatric massive transfusion groups. Therefore, large, prospective, multicenter studies are needed to identify the empiric ratio of blood products for improving outcomes of pediatric patients who need massive transfusion.
Adult ; Humans ; Incidence ; Mortality ; Plasma ; Prospective Studies ; Trauma Centers

A twenty-year-old male was diagnosed with common variable immunodecifiency (CVID) according to decreased blood level of immunoglobulins along with a history of recurrent sinopulmonary infection since early childhood, no response to prior vaccination, and the absence of all other defined immunodeficiency. Eleven months after the initiation of intravenous immunoglobulin replacement, he presented with petechiae on both lower legs for three weeks. Bone marrow exam was conducted as pancytopenia was not resolved over a month and severe aplastic anemia was diagnosed. Allogenic stem cell transplantation (Allo-SCT) with reduced intensity conditioning (RIC) enabled both a clinical resolution from propensity to infection with an appropriate production of immunoglobulins and a successful rescue of hematopoiesis. This report suggests that Allo-SCT using RIC is a potentially curable option in patients with CVID complicated by SAA if adequate efforts to minimize Allo-SCT-related complications are accompanied.
Anemia, Aplastic* ; Bone Marrow ; Common Variable Immunodeficiency* ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulins ; Leg ; Male ; Pancytopenia ; Purpura ; Stem Cell Transplantation* ; Stem Cells* ; Vaccination