Epidemiology and Mortality Analysis Related to Carbapenem-Resistant Enterobacterales in Patients After Admission to Intensive Care Units: An Observational Study.

Purpose: The prevalence of carbapenem-resistant Enterobacterales (CRE) is rapidly increasing worldwide. Patients in the intensive care unit (ICU) are susceptible to CRE infections, and the related mortality rate is increased. It is necessary to understand CRE strains and risk factors for CRE infection in the ICU, to facilitate development of effective prophylactic strategies and treatments for ICU patients. Patients and Methods: This observational study was conducted in a tertiary hospital between 2016 and 2021. The subjects were patients with CRE cultured from specimens obtained after ICU admission. Genotypes of strains of CRE and carbapenemase-producing Enterobacterales (CPE) were identified, CRE infection was distinguished from mere colonization, and the clinical course of these patients was investigated. Results: Among 327 CRE cases, 84 (25.7%) showed infection and 243 (74.3%) showed colonization. Of these patients, 138 (42.2%) died. The CRE strains were Klebsiella pneumoniae (253 cases, 77.4%), Enterobacter cloacae (44 cases, 13.5%), and Escherichia coli (15 cases, 4.6%). Among CRE cases, CPE was found in 249 (76.1%), including Klebsiella pneumoniae carbapenemase (KPC) in 164 (65.9%), and Guiana extended-spectrum (GES) in 64 (25.7%). A bedridden state, longer ICU stay, chronic kidney disease, malignancy, connective tissue disease, ICU admission for cardiac arrest, and CRE infection were associated with higher mortality, but cerebrovascular disease and ICU admission for trauma were associated with lower mortality. GES outbreak was caused by person-to-person transmission and was controlled through active surveillance. Conclusion: The frequency of K. pneumoniae and KPC was the highest, but E. cloacae and GES was characteristically high in this study. Active CRE surveillance can be helpful for controlling outbreak.

Differential identification of urine crystals with morphologic characteristics and solubility test.

BACKGROUND: Urinary crystals are the most diverse forms of urine sediments. Reference images for typical urinary crystals are common, however, but images for interpreting atypical urinary crystals are very rare. The authors reviewed various forms and solubility tests of urine crystals to interpret atypical crystals found in clinical specimens. METHODS: We reviewed textbooks on urinary crystals and articles published in PubMed. Some atypical crystals were confirmed using a solubility test. RESULTS: The classification, shape, chemical structure, and solubility of the crystals were summarized. In the solubility test, some crystals showed different results; therefore, a new solubility test was proposed based on the literature review. We presented various types of calcium oxalates. CONCLUSIONS: These review articles will be helpful in the examination of atypical crystals found in clinical specimens. The solubility test requires additional studies to discriminate the inconsistent results between the authors.

Comprehensive Laboratory Data Analysis to Predict the Clinical Severity of Coronavirus Disease 2019 in 1,952 Patients in Daegu, Korea.

BACKGROUND: Laboratory parameter abnormalities are commonly observed in COVID-19 patients; however, their clinical significance remains controversial. We assessed the prevalence, characteristics, and clinical impact of laboratory parameters in COVID-19 patients hospitalized in Daegu, Korea. METHODS: We investigated the clinical and laboratory parameters of 1,952 COVID-19 patients on admission in nine hospitals in Daegu, Korea. The average patient age was 58.1 years, and 700 (35.9%) patients were men. The patients were classified into mild (N=1,612), moderate (N=294), and severe (N=46) disease groups based on clinical severity scores. We used chi-square test, multiple comparison analysis, and multinomial logistic regression to evaluate the correlation between laboratory parameters and disease severity. RESULTS: Laboratory parameters on admission in the three disease groups were significantly different in terms of hematologic (Hb, Hct, white blood cell count, lymphocyte%, and platelet count), coagulation (prothrombin time and activated partial thromboplastin time), biochemical (albumin, aspartate aminotransferase, alanine aminotransferase, lactate, blood urea nitrogen, creatinine, and electrolytes), inflammatory (C-reactive protein and procalcitonin), cardiac (creatinine kinase MB isoenzyme and troponin I), and molecular virologic (Ct value of SARS-CoV-2 RdRP gene) parameters. Relative lymphopenia, prothrombin time prolongation, and hypoalbuminemia were significant indicators of COVID-19 severity. Patients with both hypoalbuminemia and lymphopenia had a higher risk of severe COVID-19. CONCLUSIONS: Laboratory parameter abnormalities on admission are common, are significantly associated with clinical severity, and can serve as independent predictors of COVID-19 severity. Monitoring the laboratory parameters, including albumin and lymphocyte count, is crucial for timely treatment of COVID-19.

Severe Acute Respiratory Syndrome Coronavirus-2 Antibody Responses in Hospitalized Patients with Coronavirus Disease 2019 in Daegu, Korea.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started to spread in Daegu beginning at the end of February 2020. IgG and IgM antibodies against SARS-CoV-2 were measured in hospitalized patients with COVID-19 with moderate to severe symptoms to improve the understanding of antibody responses. METHODS: We enrolled 312 patients with COVID-19 admitted to seven hospitals located in Daegu. Using serum (or plasma) samples from patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infections, both IgG and IgM antibodies were measured using commercial enzyme-linked immunosorbent assay (R-FIND CO¬VID-19 ELISA, SG medical, Seoul, Korea). RESULTS: The median value from the initial diagnosis, confirmed by SARS-CoV-2 PCR, to the sampling date was 24 days (day 1 to 88). The total positive rate of IgG was 93.9% and the positive IgM rate was 39.4%, without considering the elapsed period after diagnosis. Positive IgG and IgM rates were highest at 100.0% and 59.0%, respectively, at 3 weeks (15 - 21 days). IgG showed a high positive rate of 79.3% even within 7 days after the initial diag-nosis of the disease and maintained a positive rate of 97.8% until after 8 weeks. CONCLUSIONS: Among hospitalized patients with COVID-19, IgG was detected from the beginning of the diagnosis and persisted for an extended time period.

Comparison of clinical features and prognosis in patients with cryptogenic and secondary organizing pneumonia.

BACKGROUND: Organizing pneumonia (OP) can be diagnosed pathologically, and cryptogenic OP (COP) and secondary OP (SOP) have been classified by cause and particular underlying context. Because it is clinically difficult to differentiate between COP and SOP, this study investigated characteristics that could distinguish between COP and SOP. METHODS: The medical records of patients who underwent lung biopsy for a diagnosis of OP at a single tertiary hospital from January 2016 to December 2018 were retrospectively reviewed. RESULTS: Eighty-five patients had pathologically proven OP, including 16 diagnosed with COP and 69 diagnosed with SOP. The most common cause of SOP was infectious pneumonia, observed in 57 (82.6%) of the 69 patients, followed by cancer and radiation pneumonitis. The pathogens causing infectious pneumonia were identified in 45 (65.2%) patients. There were no differences in age, sex, and lung function between the COP and SOP groups. Median body mass index was significantly lower (P = 0.030), and median time from symptom onset to hospital admission significantly shorter (P = 0.006), in the SOP than in the COP group. Fever was more common in the SOP group (P = 0.024), and CURB 65, an index of pneumonia severity, tended to be higher in the SOP group (P = 0.017). Some laboratory results differed significantly between the two groups. Lymphocyte counts in bronchoalveolar lavage (BAL) fluid were significantly higher in the COP than in the SOP group (P = 0.012). Radiologic findings showed that effusion was more common in the SOP group (P = 0.036). There were no between-group differences in steroid use, 30 day and in-hospital mortality rates, and rates of OP outcomes and recurrences. Pneumonia recurrence rate was significantly higher in SOP patients who were than were not treated with steroids (P = 0.035). CONCLUSIONS: Infection is the main cause of SOP. Symptom onset is more rapid in patients with SOP than with COP. Some blood and BAL fluid test results differed significantly in the COP and SOP groups. Pleural effusion was more common in the SOP group but there were no differences in clinical course. Recurrence in patients with SOP was more common in those who were than were not treated with steroids.

Experience of percutaneous tracheostomy in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a highly contagious disease that causes respiratory failure. Tracheostomy is an essential procedure in critically ill COVID-19 patients; however, it is an aerosol-generating technique and thus carries the risk of infection transmission. We report our experience with percutaneous tracheostomy and its safety in a real medical setting. METHODS: During the COVID-19 outbreak, 13 critically ill patients were admitted to the intensive care unit (ICU) at Daegu Catholic University Medical Center between February 24 and April 30, 2020. Seven of these patients underwent percutaneous tracheostomy using Ciaglia Blue Rhino. The medical environment, percutaneous tracheostomy method, and COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results were retrospectively reviewed. After treatment, the COVID-19 infection status of healthcare personnel was investigated by RT-PCR. RESULTS: The ICU contained negative pressure cohort areas and isolation rooms, and healthcare personnel wore a powered air-purifying respirator system. We performed seven cases of percutaneous tracheostomy in the same way as in patients without COVID-19. Five patients (71.4%) tested positive for COVID-19 by RT-PCR at the time of tracheostomy. The median cycle threshold value for the RNA-dependent RNA polymerase was 30.60 (interquartile range [IQR], 25.50-36.56) in the upper respiratory tract and 35.04 (IQR, 28.40-36.74) in the lower respiratory tract. All healthcare personnel tested negative for COVID-19 by RT-PCR. CONCLUSIONS: Percutaneous tracheostomy was performed with conventional methods in the negative pressure cohort area. It was safe to perform percutaneous tracheostomy in an environment of COVID-19 infection.

Intravascular large B-cell lymphoma associated with myelofibrosis: A case report.

Myelofibrosis (MF) is often accompanied by chronic myeloid leukemia, hairy cell leukemia, or certain primary myeloproliferative neoplasms, but is rarely associated with lymphoid neoplasms. We herein describe a case of intravascular large B-cell lymphoma (IVLBCL) with MF. IVLBCL is a rare, aggressive type of extranodal B-cell lymphoma, defined by proliferation of lymphomatous cells within small-to medium-sized vessels. A 60-year-old woman was admitted to the hospital with anemia, thrombocytopenia and fever. Bone marrow biopsy findings included trilineage hematopoiesis, increased numbers of immature cells, markedly abnormal and enlarged megakaryocytes, and diffuse fibrosis in multiple focal areas throughout the entire bone marrow space. When the patient was first hospitalized, hepatosplenomegaly was not present. Although initially considered during differential diagnosis, an aggressive lymphoma could not be diagnosed prior to colonoscopy, which was conducted 4 weeks after admission. A biopsy of the terminal ileum revealed IVLBCL with cells with atypical nuclei. Immunophenotyping of the atypical large cells yielded a positive result for CD79a and negative results for terminal deoxynucleotidyl transferase, myeloperoxidase, CD3, CD10, CD20, B-cell lymphoma (Bcl)-2, Bcl-6 and cytomegalovirus. The patient was diagnosed with IVLBCL complicated by MF. This case may serve as a reminder that IVLBCL may be the cause of secondary MF.

Clinical response to long-term tenofovir monotherapy in Korean chronic hepatitis B patients.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is a potent nucleotide analogue recommended as first-line monotherapy for chronic hepatitis B (CHB). We investigated the clinical response to TDF monotherapy in Korean CHB patients. METHODS: A total of 90 CHB patients [55 hepatitis B e antigen (HBeAg)-positive and 35 HBeAg-negative] who received TDF monotherapy for >2year, were enrolled. Quantitative hepatitis B surface antigen (qHBsAg) levels, serum alanine aminotransferase (ALT), HBeAg, anti-HBe and HBV DNA levels were measured during treatment. Virologic response (VR) was defined as undetectable HBV DNA level. RESULTS: The cumulative incidences of complete virologic response (CVR) were 75.6% and 89.9% at months 12 and 24, respectively. The cumulative CVR rates were significantly higher in HBeAg-negative than HBeAg-positive group (P<0.001). HBeAg loss/seroconversion was observed in 21 (38.2%) out of 55 HBeAg-positive patients. One HBeAg-positive and 1 HBeAg-negative patients (2.2%) achieved HBsAg loss at months 6 and 8 of TDF therapy, respectively. Baseline HBV DNA level and qHBsAg were significant predictive factors for a CVR (P=0.001 and P<0.001, respectively). CONCLUSIONS: Virologic, serologic, biochemical responses were achieved in both HBeAg-positive and HBeAg-negative patients under 24-month TDF therapy. Monitoring using baseline HBV DNA and qHBsAg levels would be helpful to predict CVR.

Genetic Characteristics of Polycythemia Vera and Essential Thrombocythemia in Korean Patients.

BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.

Prevalence of 25-hydroxyvitamin D deficiency in Korean patients with anemia.

BACKGROUND: We investigated the prevalence and risk factors for vitamin D deficiency in Korean patients with anemia. METHODS: We included 200 anemic patients and 300 controls. Anemia was defined according to the WHO criteria. Serum 25-hydroxyvitamin D [25(OH)D] was measured using an electrochemiluminescence immunoassay. We compared serum 25(OH)D levels based on the presence and subtypes of anemia. RESULTS: We found that 91% (182/200) and 87.3% (262/300) of patients exhibited 25(OH)D inadequacies (<20 ng/ml) in the anemic (median hemoglobin (Hb), 9.6 g/dl) and control groups (median Hb 13.8 g/dl), respectively. The prevalence of 25(OH)D deficiency (<12 ng/ml) was significantly higher in the anemic group than in the control group (52.5% (105/200) vs. 25% (75/300), P < 0.0001), with an odds ratio of 3.316 (95% CI, 2.265-4.854; P < 0.0001). The prevalence of 25(OH)D deficiency was not different among anemia subtypes. Female gender and high C-reactive protein (CRP) were associated with vitamin D deficiency in anemic group. CONCLUSIONS: This study demonstrates that vitamin D deficiency is associated with anemia. Therefore, the measurement of serum 25(OH)D levels and appropriate vitamin D supplementation should be considered in anemic patients, particularly in females and patients with high CRP level.

Chronic lymphocytic leukemia in Korean patients: frequent atypical immunophenotype and relatively aggressive clinical behavior.

Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm characterized by the expansion of CD5-positive lymphocytes in peripheral blood. While CLL is the most common type of leukemia in Western populations, the disease is rare in Asians. Hence, clinical and laboratory data and studies of CLL in Asian populations have been limited. In this study, we investigated the clinical and laboratory characteristics of CLL in Korea. A total of 39 patients who had been diagnosed with CLL during the period from January 2000 to October 2010 at a single institution in Korea were examined. Clinically, 67 % of the patients were classified as having advanced Binet stages B or C. Up to 56 % of the patients had an atypical immunophenotype with high frequencies of FMC7 positivity and strong CD22 positivity. Twenty-six patients (67 %) received chemotherapy, and more than half of the treated patients (54 %) expired. The overall survival rate at 5 years was estimated at 71 %, which was lower than previously reported. These findings suggested that CLL in Korea has atypical immunophenotypes and that its clinical behavior may be more aggressive than that in Western populations.

Quantitative PCR for Etiologic Diagnosis of Methicillin-Resistant Staphylococcus aureus Pneumonia in Intensive Care Unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) requires prompt and appropriate treatment. Since methicillin-resistant Staphylococcus aureus (MRSA) is a frequent pathogen in VAP, rapid identification of it, is pivotal. Our aim was to evaluate the utility of quantitative polymerase chain reaction (qPCR) as a useful method for etiologic diagnoses of MRSA pneumonia. METHODS: We performed qPCR for mecA, S. aureus-specific femA-SA, and S. epidermidis-specific femA-SE genes from bronchoalveolar lavage or bronchial washing samples obtained from clinically-suspected VAP. Molecular identification of MRSA was based on the presence of the mecA and femA-SA gene, with the absence of the femA-SE gene. To compensate for the experimental and clinical conditions, we spiked an internal control in the course of DNA extraction. We estimated number of colony-forming units per mL (CFU/mL) of MRSA samples through a standard curve of a serially-diluted reference MRSA strain. We compared the threshold cycle (Ct) value with the microbiologic results of MRSA. RESULTS: We obtained the mecA gene standard curve, which showed the detection limit of the mecA gene to be 100 fg, which corresponds to a copy number of 30. We chose cut-off Ct values of 27.94 (equivalent to 1×10(4) CFU/mL) and 21.78 (equivalent to 1×10(5) CFU/mL). The sensitivity and specificity of our assay were 88.9% and 88.9% respectively, when compared with quantitative cultures. CONCLUSION: Our results were valuable for diagnosing and identifying pathogens involved in VAP. We believe our modified qPCR is an appropriate tool for the rapid diagnosis of clinical pathogens regarding patients in the intensive care unit.

JAK2 V617F and MPL W515L/K mutations in Korean patients with essential thrombocythemia.

JAK2 V617F and MPL W515L/K mutations have been reported in approximately 50% and 5% of the patients with essential thrombocythemia (ET), respectively. We investigated the frequency of MPL W515L/K mutations in a series of consecutive patients with ET and post-essential thrombocythemia myelofibrosis (post-ET MF). The study subjects were 63 patients diagnosed either with ET (N=59) or post-ET MF (N=4) at our institution between June 2006 and February 2010. Among them, 35 (55.6%) had the JAK2 V617F mutation. MPL W515L/K mutations were detected by direct sequencing analyses of exon 10, and 2 patients were found to harbor the following MPL mutations: W515L in 1 patient with ET and W515K in 1 patient with post-ET MF. Neither of the patients had the JAK2 V617F mutation. Thus, the frequency of MPL W515L/K mutation in Korean patients with ET/post-ETMF was 3.2% (2/63) and that in JAK2 V617F-negative ET/post-ET MF was 7.1% (2/28) [corrected]. This is the first study to report the frequency of JAK2 V617F and MPL W515L/K mutations in Korean patients with ET/post-ET MF.

A case of resistance to thyroid hormone with thyroid cancer.

Resistance to thyroid hormone (RTH) is an autosomal dominant hereditary disorder that is difficult to diagnose because of its rarity and variable clinical features. The magnitude of RTH is caused by mutations in the thyroid hormone receptor beta (TR beta) gene. We recently treated a 38-yr-old woman with RTH who had incidental papillary thyroid carcinoma. She presented with goiter and displayed elevated thyroid hormone levels with an unsuppressed TSH. She was determined to harbor a missense mutation of M310T in exon 9 of the TR beta gene, and diagnosed with generalized RTH. This mutation has not yet been reported in Korea. RTH is very rare and easily overlooked, but should be considered in patients who present with goiter and elevated thyroid hormone levels with an unsuppressed TSH. The association between thyroid cancer and RTH needs further study.

Clinical, pathological, and genetic analysis of a Korean family with thoracic aortic aneurysms and dissections carrying a novel Asp26Tyr mutation.

Non-syndromic familial thoracic aortic aneurysms and dissections (TAADs), inherited in an autosomal dominant manner in up to 19% of patients, are genetically heterogeneous. The ACTA2 gene, which encodes the vascular smooth muscle cell (SMC)-specific isoform of alpha-actin, is known to cause TAADs and occlusive vascular diseases, including coronary artery disease and premature ischemic stroke. We have investigated a Korean family with DeBakey type I aortic dissection related to pregnancy and a strong family history of TAADs. All affected family members underwent surgical repair of the ascending aorta. Other clinical features of familial TAAD, including inguinal hernias, iris flocculi, and livedo reticularis, were not observed. Histologic studies of aortic tissues showed medial degeneration and SMC hyperplasia in the aorta, consistent with previous observations. Molecular analyses of the ACTA2 gene showed a novel heterozygous missense mutation (c.76G>T; p.Asp26Tyr). Further analysis of a female patient and members of her family revealed that two affected sisters and her asymptomatic son had the same mutation. The novel Asp26Tyr mutation resides in SM alpha-actin subdomain 1 and is linked to TAAD with hypertrophy and disarray of SMCs and severe migraine, but not to livedo reticularis or iris flocculi. This study expands the spectrum of mutations of the ACTA2 gene by identifying a novel missense mutation. This is the first report of a pathologically- and genetically-confirmed family with TAAD in Korea.

Acute myeloid leukemia with del(X)(p21) and cryptic RUNX1/RUNX1T1 from ins(8;21)(q22;q22q22) revealed by atypical FISH signals.

A 57-yr-old woman was diagnosed with acute myeloid leukemia (AML) with maturation, based on morphological and cytochemical/immunophenotypic findings on bone marrow studies. Conventional cytogenetic analysis using bone marrow cells revealed terminal deletion of the short arm of an X chromosome as 46,X,del(X)(p21)[8]/46,XX[12]. On the other hand, fluorescence in situ hybridization (FISH) for the RUNX1/RUNX1T1 (formerly AML1/ETO) rearrangement revealed 86% interphase nuclei with one fusion signal, which was found to be on the long arm of chromosome 8 on metaphase FISH, indicating the RUNX1/RUNX1T1 rearrangement by cryptic insertion of the RUNX1 gene. Molecular genetic study by reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the presence of the chimeric transcript. The final karyotype was 46,X,del(X)(p21).ish ins(8;21)(q22;q22q22)(RUNX1T1+,RUNX1+;RU NX1+,RUNX1T1-)[8]/46,XX[12]. In addition to the cryptic RUNX1/RUNX1T1 rearrangement, this is the first report of partial deletion of an X chromosome as an additional cytogenetic aberration in AML with RUNX1/RUNX1T1.

Glucose biosensors: an overview of use in clinical practice.

Blood glucose monitoring has been established as a valuable tool in the management of diabetes. Since maintaining normal blood glucose levels is recommended, a series of suitable glucose biosensors have been developed. During the last 50 years, glucose biosensor technology including point-of-care devices, continuous glucose monitoring systems and noninvasive glucose monitoring systems has been significantly improved. However, there continues to be several challenges related to the achievement of accurate and reliable glucose monitoring. Further technical improvements in glucose biosensors, standardization of the analytical goals for their performance, and continuously assessing and training lay users are required. This article reviews the brief history, basic principles, analytical performance, and the present status of glucose biosensors in the clinical practice.

Multiplex ligation-dependent probe amplification screening of isolated increased HbF levels revealed three cases of novel rearrangements/deletions in the beta-globin gene cluster.

Investigations of naturally occurring mutations, such as the deletional thalassaemias and hereditary persistence of fetal haemoglobins (HPFHs), have brought many insights into human globin switching, but limited data have been reported so far. We selected 15 individuals with elevated fetal haemoglobin (HbF) levels (>5%) from a previous screening of 27 006 Korean individuals and analysed dosage changes of the globin gene cluster using multiplex ligation-dependent probe amplification (MLPA). Dosage changes detected by the MLPA probes were followed up with gap-polymerase chain reaction and sequence analysis. Three subjects were found to have deletions in the globin gene cluster, including a beta-thalassaemia due to deletion of HBB (beta-globin gene), an HPFH due to deletions of HBD (delta-globin gene) and HBB, and an HPFH due to a novel HBG2-HBG1 fusion gene consisting of exons 1 and 2 of HBG2 ((G)gamma-globin gene) and exon 3 of HBG1 ((A)gamma-globin gene). The case with the HBG2-HBG1 fusion suggested the existence of another mechanism for the reactivation of HBG2 and HBG1. The IVS2 of HBG2 and HBG1might play a role in HbF regulation, and combinations of specific polymorphisms could influence the reactivation of these genes in adults.

A novel initiation codon mutation in the ribosomal protein S17 gene (RPS17) in a patient with Diamond-Blackfan anemia.

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure syndrome characterized by pure red cell aplasia, various congenital anomalies, and cancer predisposition. We report a novel mutation in the RPS17 gene in a Korean patient with DBA. The mutation occurred in the translation initiation codon, changing Atg to Gtg (c.1A>G), thus disrupting the natural start of the RPS17 protein biosynthesis. This is the third case of DBA from a RPS17 mutation in the literature and is the second case of a RPS17 mutation in the translation initiation codon, following c.2T>G.

The prevalence and risk factors for gallstone disease.

Gallstone disease is one of the most prevalent gastrointestinal disorders. In addition, the costs associated with the diagnosis and treatment of gallstone disease have been rapidly increasing. The etiology and pathogenesis of gallstone disease remains incompletely understood. Gallstone formation may result from a complex interaction of genetic and environmental factors. This article reviews the prevalence and risk factors associated with gallstone disease. Understanding the pathogenesis of gallstone disease could lead to the development of better therapeutic and preventive strategies for dealing with this disease.