Child ; Humans ; Granulomatous Disease, Chronic/complications* ; Pneumonia

Summary Sporotrichosis is a rare and chronic granulomatous subcutaneous mycotic infection caused by a dimorphic fungus, Sporothrix schenckii. We describe a patient with disseminated cutaneous sporotrichosis who was later diagnosed with myeloproliferative neoplasm and discuss the challenges and importance in diagnosing this rare condition.
Sporotrichosis ; Granulomatous Disease, Chronic ; Myeloproliferative Disorders

OBJECTIVE: To explore the genetic basis for a child featuring Chediak-Higashi syndrome (CHS). METHODS: Clinical manifestations and results of auxiliary examination of the proband were analyzed. The proband was subjected to whole exome sequencing, and the results were verified by Sanger sequencing. Correlation between the genotype and clinical phenotype was analyzed. RESULTS: The proband showed partial skin albinism, recurrent respiratory infection and other immune deficiencies. Genetic testing showed that he has harbored c.2437C>T (p.Arg813*) and c.6077dupA (p.Tyr2026fs) (NM_000081) compound heterozygous variants of the LYST gene, for which his parents were both carriers. Neither variant was reported previously. HEAT repeats domain was frequently associated with more severe phenotype of CHS (81.6%), whilst no variant has been found in the PH_BEACH domain. CONCLUSION This study has enriched the spectrum of LYST gene variants associated with CHS and enabled clinical diagnosis, prenatal diagnosis and prognostic evaluation for the child.
Male ; Humans ; Chediak-Higashi Syndrome/genetics* ; Vesicular Transport Proteins/genetics* ; Heterozygote ; Genetic Testing ; China

OBJECTIVE: To detect pathological variant in two patients with Chediak-Higashi syndrome (CHS) from a consanguineous family and to explore its genotype-phenotype correlation. METHODS: Clinical data was collected for this pedigree. Genomic DNA was prepared from probands' peripheral leukocytes and their relatives' fingernail. Whole exome sequencing and Sanger sequencing were carried out to detect potential variant of the LYST gene. RESULTS: The proband presented with partial oculocutaneous albinism, immunodeficiency and acidophilic inclusion body in bone marrow and blood smears. A novel homozygous nonsense variant c.8782C>T (p.Gln2928*) was identified in exon 34 of the LYST gene in the sib pair. The same variant was found to be in heterozygous status in 6 unaffected individuals from the pedigree. CONCLUSION Above result enriched the mutational spectrum of CHS and provided a basis for genetic counseling and prenatal diagnosis for this pedigree.
Chediak-Higashi Syndrome ; genetics ; Exons ; Heterozygote ; Humans ; Mutation ; Pedigree ; Sequence Analysis, DNA ; Vesicular Transport Proteins ; genetics ; Whole Exome Sequencing

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.
Agammaglobulinemia ; Diagnosis ; Exome ; Flow Cytometry ; Genetic Testing ; Granulomatous Disease, Chronic ; Humans ; Immunophenotyping ; Korea ; Leukocytes ; Lymphocyte Subsets ; Lymphohistiocytosis, Hemophagocytic ; Phenotype ; Retrospective Studies ; Seoul ; Severe Combined Immunodeficiency ; Tertiary Healthcare

PURPOSE: This study aimed to confirm the mediating effect of job involvement in the relationship between grit and turnover intention among nurses working at university hospitals. METHODS: Participants included 437 nurses from university hospitals located in C city, Gyeongnam. Data were collected from January 8 to 19, 2018, using self-report questionnaires. Data were analyzed using the t-test, analysis of variance, Scheffe's test, Pearson's correlation coefficient, and multiple regression, with the SPSS/22.0 program. A mediation analysis was performed according to the Baron and Kenny, and bootstrapping methods. RESULTS: There were significant relationships between grit and job involvement (r=.40, p<.001), grit and turnover intention (r=−.29, p<.001), and turnover intention and job involvement (r=−.52, p<.001). Job involvement showed partial mediating effects in the relationship between grit and turnover intention. CONCLUSION: Grit increased job involvement and lowered turnover intention. Therefore, to reduce nurses' turnover intention, it is necessary to develop a program and strategies to increase their grit.
Hospitals, University ; Intention ; Job Syndrome ; Negotiating ; Personnel Turnover

OBJECTIVE: To investigate the clinical efficacy of haploid hematopoietic stem cells (haplo-HSC) combined with third-party umbilical cord blood (tpCB) transplantation in the treatment of X-linked chronic granulomatous disease (X-CGD). METHODS: The clinical data of 26 boys with X-CGD were retrospectively analyzed who were admitted to the Sixth Medical Center of PLA General Hospital between April 2014 and March 2018. All the patients were treated with haplo-HSC combined with tpCB transplantation. The median age of the patients was 3.5 years. The donor was the father in 25 cases and an aunt in 1 case. Transplantation was 5/6 HLA-matched in 9 cases, 4/6 in 12 cases, and 3/6 in 5 cases. The patients received busulfan, cyclophosphamide, fludarabine, or anti-thymocyte globulin for myeloablative preconditioning. Cyclosporine A and mycophenolate mofetil were used for prevention of acute graft-versus-host disease (aGVHD). Then the patients were treated with haploid bone marrow hematopoietic stem cells combined with tpCB transplantation on day 1 and haploid peripheral hematopoietic stem cells on day 2. The counts of median donor total nucleated cells, CD34 cells, and CD3 cells were 14.6×10/kg, 5.86×10/kg, and 2.13×10/kg respectively. RESULTS: The median time to neutrophil and platelet engraftment was 12 and 23 days after transplantation respectively. Full donor hematopoietic chimerism was observed on day 30. Twenty-five cases were from haplo-HSC and 1 was from cord blood. No primary implant failure and implant dysfunction occurred, and secondary implant failure occurred in one case. The NADPH oxidase activity returned to normal one month after transplantation. The incidence of grade I-II aGVHD and grade III-IV aGVHD was 35% and 15% respectively. Chronic GVHD (cGVHD) of the skin occurred in one case, and no progression was observed after steroid administration. During the follow-up period of 6-51 months, 25 patients survived, of whom 24 were disease-free (23 patients without cGVHD and 1 with cGVHD of the skin) and NADPH oxidase activity returned to normal; one patient developed secondary implant failure but survived; one patient died of viral interstitial pneumonia 16 months after transplantation. The 5-year event-free survival rate and overall survival rate were 81%±12% and 89%±10% respectively. CONCLUSIONS Haplo-HSC combined with tpCB transplantation is one of the effective methods for the treatment of X-CGD in children.
Child, Preschool ; Cord Blood Stem Cell Transplantation ; Graft vs Host Disease ; Granulomatous Disease, Chronic ; Haploidy ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Male ; Retrospective Studies ; Transplantation Conditioning

OBJECTIVETo explore the genetic basis for a pedigree affected with Chediak-Higashi syndrome (CHS).

METHODSClinical data of two CHS patients from the pedigree was collected and analyzed. Targeted next generation sequencing and Sanger sequencing were conducted to detect potential mutation of the LYST gene.

RESULTSBoth patients presented immunodeficiency, oculocutaneous albinism, and acidophilic inclusion body on bone marrow and blood smears. A homozygous c.6077_6078insA (p.Tyr2026Terfs) mutation was detected in the LYST gene in both patients.

CONCLUSIONGenetic testing can play an important role in the diagnosis of CHS.

Chediak-Higashi Syndrome ; genetics ; Female ; Genetic Testing ; Humans ; Infant ; Infant, Newborn ; Mutation ; Pedigree ; Vesicular Transport Proteins ; genetics

BACKGROUND: Leprosy is a contagious chronic granulomatous disease and is a disease that is associated with defects in cellular immunity. A high prevalence of hepatitis C virus infection in leprosy patients has been reported in several African countries, Yemen, Brazil and Japan. In Korea, it's seropositivity was reported as 8.33%(2001), 39.3%(2002), 35.1%(2009) and 16.0%(2009) on Korean Leprosy Bulletin. OBJECTIVE: In the meantime, the studies were limited to the subjects in a specific region, and the number of subjects was not enough, so it was not enough to evaluate the hepatitis C virus seropositivity of persons affected by leprosy in Korea. So this study was conducted to evaluate the it's seropositivity in settlement villages nationwide. METHOD: This study was conducted that the mobile team visited the resettlement villages nationwide from 2009 to 2017 and conducted on persons affected by leprosy and residents residing in resettlement village. Obtained serums were assayed by the ADVIA Centaur HVC(IgG antibodies to Hepatitis C Virus) reagent using a Siemens ADVIA Centaur CP instrument. The results of persons affected by leprosy and residents were compared, and the difference of seropositivity among the groups(male and female, multibacillary and paucibacillary, locations of resettlement villages) was evaluated. RESULT: The results of hepatitis C virus antibody positivity of 1669 persons affected by leprosy subjects and 185 residents of resettlement villages were 28.46% in persons affected by leprosy and 6.49% in residents(Pearson's Chi-Square test, P = 0.00). In persons affected by leprosy, that were 31.99%(male) and 26.84%(female)(Pearson's Chi-Square test, P = 0.06) and were 29.97%(multibacillary) and 25.36%(paucibacillary)(Pearson's Chi-Square test, P = 0.05). That of Seoul(48.28%), Busan(43.78%) and Chungbuk Province(35.94%) were highly positive and that of Gangwon Province(20.34%) was lowly positive(Fisher's Exact test P = 0.002). CONCLUSION: In this study, we found that hepatitis C virus antibody positivity rate was high in persons affected by leprosy in Korea. In order to explain the high positive rate, further studies will be needed. Also, through various approaches including assessment of HCV RNA to the subjects who were judged to be positive for antibody test in the future, a comprehensive evaluation of hepatitis C and its countermeasures are needed.
Antibodies ; Brazil ; Chungcheongbuk-do ; Female ; Gangwon-do ; Granulomatous Disease, Chronic ; Hepacivirus* ; Hepatitis C* ; Hepatitis* ; Humans ; Immunity, Cellular ; Japan ; Korea* ; Leprosy* ; Methods ; Prevalence ; RNA ; Yemen

During the past decades, there has been a great evolution in the field of fetal therapy for congenital defects. Prenatal screening or diagnostic methods including non-invasive and invasive methods and fetal ultrasound have led to earlier and more accurate diagnosis of congenital anomalies. Recent advances in several therapeutic techniques including ultrasound-guided needle therapy, laser therapy or fetal endoscopy, have allowed some fetuses at risk with anatomical defects, to be corrected in utero but still, its clinical indications remain limited. Over the last 30 years, many researchers found usefulness of pluripotent stem cells from amniotic fluid and placenta because they are sources of diverse progenitor cell populations called mesenchymal stem cells. In some human conditions like severe combined immunodeficiency syndrome and chronic granulomatous disease, fetal therapy using stem cell replacement showed some promising results in researches but more studies are required to apply in clinical settings. The aim of this article is to summarize a current status and future perspective of stem cell therapy for treatment of congenital fetal anomalies.
Amniotic Fluid ; Congenital Abnormalities ; Diagnosis ; Endoscopy ; Female ; Fetal Therapies* ; Fetus ; Granulomatous Disease, Chronic ; Humans ; Laser Therapy ; Mesenchymal Stromal Cells ; Needles ; Placenta ; Pluripotent Stem Cells ; Prenatal Diagnosis ; Severe Combined Immunodeficiency ; Stem Cells* ; Ultrasonography