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Purpose@#Demand for genetic counseling on cancer predisposition syndrome is increasing. We evaluated the psychological effect on counselees after genetic counseling at a clinic in a single center. @*Materials and Methods@#We surveyed a total of 72 enrolled participants who visited a genetic counseling clinic at the Samsung Medical Center (SMC). The initial survey was conducted before the first genetic counseling session, and the second survey was conducted after the second genetic counseling session. A total of 43 participants completed both the initial and second surveys. @*Results@#The initial survey of 72 participants indicated higher feelings of guilt in the group with religion, higher depression and anxiety in the group with a diagnosis of self, and higher anxiety in the group on self-referral to the genetic counseling clinic.In the completed survey of 43 participants, overall decreased depression was observed after the second genetic counseling session (P=0.013). Risk perception and anxiety decreased in the group diagnosed with benign variant/variant of uncertain significance (BV/VUS, 25/3) and increased in the group diagnosed with pathogenic variant (PV, 15). Risk perception and anxiety differed between the BV/VUS and PV groups (P<0.001 and P=0.03, respectively). @*Conclusion@#The genetic counseling clinic at the SMC was effective in ameliorating the depression score. Assessment of survey results revealed different depression scores, feelings of guilt and anxiety, and different effects of the genetic counseling clinic, depending on the subgroups. Understanding the needs and psychological characteristics of different groups is necessary for improving genetic counseling services.
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Purpose@#Demand for genetic counseling on cancer predisposition syndrome is increasing. We evaluated the psychological effect on counselees after genetic counseling at a clinic in a single center. @*Materials and Methods@#We surveyed a total of 72 enrolled participants who visited a genetic counseling clinic at the Samsung Medical Center (SMC). The initial survey was conducted before the first genetic counseling session, and the second survey was conducted after the second genetic counseling session. A total of 43 participants completed both the initial and second surveys. @*Results@#The initial survey of 72 participants indicated higher feelings of guilt in the group with religion, higher depression and anxiety in the group with a diagnosis of self, and higher anxiety in the group on self-referral to the genetic counseling clinic.In the completed survey of 43 participants, overall decreased depression was observed after the second genetic counseling session (P=0.013). Risk perception and anxiety decreased in the group diagnosed with benign variant/variant of uncertain significance (BV/VUS, 25/3) and increased in the group diagnosed with pathogenic variant (PV, 15). Risk perception and anxiety differed between the BV/VUS and PV groups (P<0.001 and P=0.03, respectively). @*Conclusion@#The genetic counseling clinic at the SMC was effective in ameliorating the depression score. Assessment of survey results revealed different depression scores, feelings of guilt and anxiety, and different effects of the genetic counseling clinic, depending on the subgroups. Understanding the needs and psychological characteristics of different groups is necessary for improving genetic counseling services.
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Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a subtype of CMC caused by gain-of-function (GOF) mutation of the signal transducer and the activator of transcription 1 (STAT1) protein. GOF mutation of STAT1 disrupts Th17 cell differentiation and causes susceptibility to candida infection in mucous membranes. Although genetic testing is crucial to diagnose AD-CMC, a simple and fast diagnostic tool is required for the management and reduction of complications associated with infection. Flow cytometry (FCM) is suggested for the measurement of intracellular phosphorylated STAT1 (pSTAT1) in a stimulated status. Here, we report the application of FCM to show the activation status of STAT signaling in a 24-year-old female patient diagnosed with AD-CMC. Compared to the controls, the patient’s T cells showed increased levels of pSTAT1 after stimulation by interferon-γ and lesser extent of inhibition caused by an inhibitor. To the best of our knowledge, this is the first evaluation of the usefulness of FCM as an alternative diagnostic and monitoring tool of GOF STAT1 in Korea.
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Background@#Therapeutic drug monitoring (TDM) is clinically recommended for vancomycin and aminoglycoside antibiotics owing to their narrow therapeutic range and nephrotoxicity at high concentrations in the blood. This study was conducted to investigate the current status of TDM of vancomycin and aminoglycosides in Korean clinical laboratories. @*Methods@#Ten organizations participated in this survey. Vancomycin, amikacin, gentamicin, and tobramycin were prepared in three samples of five or six different concentrations. Data from each institution were calculated for the mean, standard deviation, within-day, between-day, and within-laboratory precision. The results from each institution were compared in various ways. @*Results@#Six instruments from three manufacturers were used. Samples with the lowest drug concentration were reported as below the lower limit of quantitation in most laboratories. Coefficients of variation for within-laboratory values ranged from 1.1% to 10.9% for vancomycin, 0.8% to 18.2% for amikacin, 1.2% to 7.8% for gentamicin, and 1.3% to 6.1% for tobramycin. Based on the overall results of the participants, only one institution’s vancomycin samples standard deviation index exceeded 3, with all other values below 2. The College of American Pathologist criteria were met by all institutions; however, measurement of vancomycin in one laboratory and of gentamycin in three laboratories failed to meet the Royal College of Pathologists of Australasia acceptance criteria. @*Conclusions@#Although the precision of the antibiotic test in individual institutions was excellent, there was a difference in the measured values between laboratories. Harmonization of antibiotic TDM is needed to reduce inconsistencies in results.
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Autosomal dominant chronic mucocutaneous candidiasis (AD-CMC) is a subtype of CMC caused by gain-of-function (GOF) mutation of the signal transducer and the activator of transcription 1 (STAT1) protein. GOF mutation of STAT1 disrupts Th17 cell differentiation and causes susceptibility to candida infection in mucous membranes. Although genetic testing is crucial to diagnose AD-CMC, a simple and fast diagnostic tool is required for the management and reduction of complications associated with infection. Flow cytometry (FCM) is suggested for the measurement of intracellular phosphorylated STAT1 (pSTAT1) in a stimulated status. Here, we report the application of FCM to show the activation status of STAT signaling in a 24-year-old female patient diagnosed with AD-CMC. Compared to the controls, the patient’s T cells showed increased levels of pSTAT1 after stimulation by interferon-γ and lesser extent of inhibition caused by an inhibitor. To the best of our knowledge, this is the first evaluation of the usefulness of FCM as an alternative diagnostic and monitoring tool of GOF STAT1 in Korea.
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Background@#Therapeutic drug monitoring (TDM) is clinically recommended for vancomycin and aminoglycoside antibiotics owing to their narrow therapeutic range and nephrotoxicity at high concentrations in the blood. This study was conducted to investigate the current status of TDM of vancomycin and aminoglycosides in Korean clinical laboratories. @*Methods@#Ten organizations participated in this survey. Vancomycin, amikacin, gentamicin, and tobramycin were prepared in three samples of five or six different concentrations. Data from each institution were calculated for the mean, standard deviation, within-day, between-day, and within-laboratory precision. The results from each institution were compared in various ways. @*Results@#Six instruments from three manufacturers were used. Samples with the lowest drug concentration were reported as below the lower limit of quantitation in most laboratories. Coefficients of variation for within-laboratory values ranged from 1.1% to 10.9% for vancomycin, 0.8% to 18.2% for amikacin, 1.2% to 7.8% for gentamicin, and 1.3% to 6.1% for tobramycin. Based on the overall results of the participants, only one institution’s vancomycin samples standard deviation index exceeded 3, with all other values below 2. The College of American Pathologist criteria were met by all institutions; however, measurement of vancomycin in one laboratory and of gentamycin in three laboratories failed to meet the Royal College of Pathologists of Australasia acceptance criteria. @*Conclusions@#Although the precision of the antibiotic test in individual institutions was excellent, there was a difference in the measured values between laboratories. Harmonization of antibiotic TDM is needed to reduce inconsistencies in results.
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Since the American College of Medical Genetics and Genomics and Association of Molecular Pathology published their guidelines in 2015, most interpretations of genetic tests have followed them. However, all variants have only limited evidence along 28 interpretation standards, especially de novo variants. When de novo variants, which are classified as variants of uncertain significance (VUS) due to lack of evidence, are detected, segregation in the affected family could provide an important key to clarifying the variants. Autosomal dominant polycystic kidney disease is the most common inherited kidney disorder with pathogenic variants in the PKD1 or PKD2 genes. We detected a novel in-frame deletion variant in the PKD1 gene, c.7575_7577del (p.(Cys2526del)), which was interpreted as a VUS. We analyzed this variant in a Korean family to decide for segregation. Here, we report the variant as a likely pathogenic variant based on the evidence of segregation in three affected relatives and two unaffected members.
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Gorlin–Goltz syndrome, also known as basal cell nevus syndrome, is a condition that affects several body parts and increases the risk of developing various cancerous and noncancerous tumors. This syndrome is mostly caused by the pathogenic variants of the PTCH1 and SUFU genes; however, it is rarely diagnosed due to limited prevalence. PTCH2 has rarely been identified as a pathogenic variant in patients with the Gorlin–Goltz syndrome in China and Japan. Here, we report the case of a 30-year-old woman who was diagnosed with the Gorlin–Goltz syndrome—based on multiple calcifications on the body—who carried a frame shift pathogenic variant of the PTCH2 gene (c.1172_1173del) identified via whole exome sequencing. The patient did not present the typical phenotypes of the Gorlin–Goltz syndrome, such as basal cell carcinoma, palmar/plantar pits, macrocephaly, and keratocystic odontogenic tumors. Based on these observations, we suggest that a pathogenic variant of PTCH2 can manifest a milder phenotype of the Gorlin–Goltz syndrome.
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PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.
Sujet(s)
Humains , Agammaglobulinémie , Diagnostic , Exome , Cytométrie en flux , Dépistage génétique , Granulomatose septique chronique , Immunophénotypage , Corée , Leucocytes , Sous-populations de lymphocytes , Lymphohistiocytose hémophagocytaire , Phénotype , Études rétrospectives , Séoul , Immunodéficience combinée grave , Soins de santé tertiairesRÉSUMÉ
Actinotignum schaalii is an emerging uropathogen; however, routine culture protocols and usual phenotypic methods do not allow for easy detection and identification. Herein, we report the first Korean case of urinary tract infection caused by A. schaalii in a 79-year-old patient with prostate cancer. A gram-positive rod bacterium was isolated from the patient's urine after 2 days of culture and identified as A. schaalii using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and DNA target sequencing.
Sujet(s)
Sujet âgé , Humains , ADN , Spectrométrie de masse , Tumeurs de la prostate , Infections urinaires , Voies urinairesRÉSUMÉ
BACKGROUND: Fluorescence in situ hybridization (FISH) analysis can provide important information in the management of patients with hematologic malignancies. However, FISH performed in addition to G-banded karyotype can be labor-intensive and expensive. The aim of this study was to evaluate whether FISH gives additional information in the setting of adequate conventional cytogenetics in cases of hematologic malignancies. METHODS: Bone marrow aspirates were obtained from 135 patients at diagnosis (56 AML, 32 MDS, 20 ALL, and 27 MM) between 2005 and 2010. Interphase FISH was performed using the following probes: BCR/ABL1, AML1/ETO, PML/RARA, CBFB, MLL, EGR1, CEP8, and D7S486 for AML; CEP8, D20S108, EGR1, and D7S486 for MDS; BCR/ABL1, MLL, CDKN2A (p16), ETV6, and 6q21/c-myc for ALL; IgH, TP53, D13S25, IgH/CCND1, IgH/MAF, IgH/FGFR3, and 1q21/8p21 for MM. We compared the results of FISH with the corresponding aberrations identified by G-banded karyotype. RESULTS: Additional genetic aberrations detected by FISH (which were not identified by G-banded karyotype) were 4%, 9%, 50%, and 67% in AML, MDS, ALL, and MM, respectively. In ALL, CDKN2A and ETV6 FISH revealed additional genetic aberrations in 33% and 28% of cases, respectively. In MM, FISH was of benefit in detecting IgH, D13S25, TP53, and 1q21 rearrangements, not detected by G-banded karyotype (31%, 36%, 20%, and 40%, respectively). CONCLUSION: These results suggest that performing FISH in addition to G-banded karyotype may contribute little additional genetic information in AML and MDS, whereas routine FISH analysis appears to be an efficient screening method in ALL and MM.
Sujet(s)
Humains , Moelle osseuse , Cytogénétique , Fluorescence , Tumeurs hématologiques , Hybridation in situ , Interphase , Caryotype , Leucémie aigüe myéloïde , Dépistage de masse , Myélome multiple , Syndromes myélodysplasiques , Leucémie-lymphome lymphoblastique à précurseurs B et TRÉSUMÉ
BACKGROUND: In a previous report, epinephrine was found to markedly improve the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl. In this study we evaluated the effects of adding epinephrine to patient-controlled epidural analgesia (PCEA) based on a bupivacaine and fentanyl mixture after gynecological surgery. METHODS: Forty women undergoing lower abdominal gynecologic surgery under general anesthesia were randomized in a double-blind fashion to receive one of two regimens of; PCEA; 0.0625% bupivacaine with 2 microgram/ml fentanyl and 2 microgram/ml epinephrine for the Epinephrine group, or 0.0625% bupivacaine with 2 microgram/ml fentanyl for the No-epinephrine group after standardized combined epidural and general anesthesia. PCEA settings for the two groups were identical (4 ml/hr continuous background infusion, 2 ml bolus dose, 20 min lock-out period). Visual analogue scale (VAS) for pain at rest and on coughing, total volume infused, number of bolus infusions, and side effects such as nausea, vomiting, sedation, pruritus and motor block were recorded 2, 6, 12, 24, 36 and 48 hr postoperatively. Data are means +/- SD. RESULTS: No differences in VAS scores at rest and on coughing were observed between the groups. Incidences of hypotension and other side effects did not differ between the groups. Total volume infused was lower in the epinephrine group than in the control group at 24 hr (111+/-21 ml vs. 134+/-27 ml, P < 0.05) and at 48 hr (119+/-46 ml vs. 233+/-26 ml, P < 0.05). Similarly, the number of bolus infusions was lower in the epinephrine group than in the control group at 24 hr (8+/-6 vs 13+/-6, P < 0.05) and at 48 hr (12+/-8 vs 20+/-13, P < 0.05). CONCLUSIONS: Epinephrine lowers the dose of bupivacaine and fentanyl needed for PCEA after lower abdominal surgery without reducing the occurrence of side effects.