Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH. Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled. Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed. Conclusion These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Despite the availability of therapies to treat patients with immune thrombocytopenia (ITP), there is currently little data from randomized trials to assist clinicians in managing patients. The evidence-based guidelines of the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) are intended to support patients and physicians in the management of ITP. Experts from the KSHAAWP discussed and described this guideline according to the current treatment situation for ITP in Korea and finalized the guidelines. The expert panel recommended the management of ITP in adult and pediatric patients with newly diagnosed, persistent, and chronic disease refractory to first-line therapy with minor bleeding. Management approaches include observation and administration of corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, and thrombopoietin receptor agonists. Currently, evidence supporting strong recommendations for various management approaches is lacking. Therefore, a large focus was placed on shared decision-making, especially regarding second-line treatment.

Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. Materials and Methods: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m2/day of fludarabine for 5 or 6 days were analyzed. Results: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26–1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II–IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. Conclusion RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.

BACKGROUND AND OBJECTIVES: Proficient differentiation of human pluripotent stem cells (hPSCs) into specific lineages is required for applications in regenerative medicine. A growing amount of evidences had implicated hormones and hormone-like molecules as critical regulators of proliferation and lineage specification during in vivo development. Therefore, a deeper understanding of the hormones and hormone-like molecules involved in cell fate decisions is critical for efficient and controlled differentiation of hPSCs into specific lineages. Thus, we functionally and quantitatively compared the effects of diverse hormones (estradiol 17-β (E2), progesterone (P4), and dexamethasone (DM)) and a hormone-like molecule (retinoic acid (RA)) on the regulation of hematopoietic and neural lineage specification. METHODS AND RESULTS: We used 10 nM E2, 3 μM P4, 10 nM DM, and 10 nM RA based on their functional in vivo developmental potential. The sex hormone E2 enhanced functional activity of hematopoietic progenitors compared to P4 and DM, whereas RA impaired hematopoietic differentiation. In addition, E2 increased CD34⁺CD45⁺ cells with progenitor functions, even in the CD43⁻ population, a well-known hemogenic marker. RA exhibited lineage-biased potential, preferentially committing hPSCs toward the neural lineage while restricting the hematopoietic fate decision. CONCLUSIONS: Our findings reveal unique cell fate potentials of E2 and RA treatment and provide valuable differentiation information that is essential for hPSC applications.
Dexamethasone ; Humans ; Induced Pluripotent Stem Cells ; Pluripotent Stem Cells ; Progesterone ; Regenerative Medicine ; Tretinoin

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

BACKGROUND: Although photodynamic therapy (PDT) is widely performed for acne, little is known about its exact therapeutic mechanism. OBJECTIVE: We aimed to estimate the efficacy and safety of PDT on acne and to discover its mode of action. METHODS: We performed PDT on 12 patients with mild to moderate acne. The clinical efficacy was assessed by counting the acne lesions and measuring the sebum secretion before and after PDT. In addition, we took biopsy samples from the peri-lesional areas before and after 3-session of PDT. To examine the degree of apoptosis of the sebaceous follicles, TUNEL assay was performed. To investigate the changes of toll-like receptor (TLR)-2 and TLR-4 expression after PDT, immunohistochemical stainings were also carried out. Finally, we performed TUNEL assay using the cultured sebocytes to confirm the apoptosis of sebocytes in vitro after PDT. RESULTS: There was a significant reduction in the number of inflammatory acne lesions after PDT, compared to baseline (p<0.05). Sebum excretion significantly decreased 2 weeks after the first PDT session except for one patient (p<0.05). The TUNEL positive cells in the peri-lesional sebaceous glands after PDT markedly increased, compared with those of before PDT. A decrease in TLR-2 and TLR-4 expression by sebaceous glands and epidermis after PDT was 50% and 30%, respectively. CONCLUSION: Our results demonstrate that apoptosis of the sebaceous glands is associated with improvement of acne by PDT. PDT has shown to down-regulate TLR-2 and TLR-4 expression in the sebaceous glands and epidermis of acne patients.
Acne Vulgaris ; Apoptosis ; Biopsy ; Epidermis ; Humans ; In Situ Nick-End Labeling ; Photochemotherapy ; Sebaceous Glands ; Sebum ; Toll-Like Receptors ; Triazenes

Insular lobe seizure (ILS) is very rare and ictal focus has not been documented by neuroimaging studies. Clinical characteristics consist of clearly preserved consciousness, visceral sensation, somatomotor symptoms, and dysphonic or dysarthric speech. We report a 34-year-old female with ILS, manifesting as first onset status epilepticus. SISCOM and SPM analysis through brain MRI and 18F FDG PET-CT reveals ictal focus on the bilateral claustrum, which has a close relationship with insula anatomically. This is the first case report in Korea.
Adult ; Basal Ganglia* ; Brain ; Consciousness ; Female ; Humans ; Korea ; Magnetic Resonance Imaging ; Neuroimaging ; Seizures* ; Sensation ; Status Epilepticus*

BACKGROUND: Anemia in chronic renal failure plays an important rolr in increasing morbidity of dialysis patients. The causes of the anemia are multifactorial. With using of erythropoietin(EPO), most of uremia-induced anemia can be overcome. However, about 10% of renal failure patients shows EPO-resistant anemia. Hyporesponsiveness to EPO has been realted to many factors: iron deficiency, aluminum intoxication, inflammations, malignancies and secondary hyperparathyroidism. So I evailuated the improvement of EPO responsiveness after correction of above several factors. MATERIALS AND METHODS: Seventy-two patients on hemodialysis over 6 months were treated with intravenous ascorbic acid(IVAA, 300 mg t.i.w. for 12 weeks). After administration of IVAA for 12 weeks,patients were classified into several groups according to iron status, serum aluminum levels and i-PTH levels. Indivisualized treatments were performed; increased iron supplement for absolute iron deficiency, active vitamin D3 for secondary hyperparathyroidism and desferrioxamine(DFO, 5 mg/kg t.i.w.) for aluminum intoxication or hyperferritinemia. RESULTS: 1) Results of IVAA therapy for 12 weeks on all patients(n=72) Hemoglobin levels at 2,4,6 week were significantly elevated compared to baseline. but those of hemoglobin at 8, 10, 12 week were not significantly different. 2) Result of IVAA therapy for 20 weeks on patients with 100 microgram/1< or =ferritin<500 microgram/1 and transferrin saturation(Tsat) below 30%(n=30) After treatment of IVAA for 12 weeks, patients were evaluated the response of therapy according to iron status. Patient with 100 microgram/1< or =ferritin?500 microgram/1 and Tsat below 30% showed the most effective response. These patients were treated further for 8 weeks. Hemoglobin levels at 2, 4 week were significantly increased compared to baseline with significantly reduced doses of EPO at 2, 4, 10, 12, 16, 20 week. Concomitantly significantly improvement of Tsat at 2, 6, 16, 20 week compared to baseline were identified. 3) Result of IVAA therapy for 12 weeks followed by DFO therapy for 8 weeks on patients with serume aluminum above 4 microgram/1(n=12) Hemoglobin levels were not significantly increased during IVAA therapy for 12 weeks but dosages of EPO were significantly decreased at 2, 4, 6, 8 week during DFO therapy compared to pre-treatment status. CONCLUSION: IVAA can be helpful for the treatment of the anemia caused by functional iron deficiency and can reduce the dosage of EPO for anemia correction. And administration of low dose DFO, in cases of increased serum aluminum level, can reduce the requirment of EPO.
Aluminum ; Anemia ; Ascorbic Acid ; Cholecalciferol ; Deferoxamine ; Dialysis ; Erythropoietin* ; Humans ; Hyperparathyroidism, Secondary ; Inflammation ; Iron ; Kidney Failure, Chronic ; Renal Dialysis* ; Renal Insufficiency ; Transferrin

Mucormycosis is an uncommon, frequently fatal, opportunistic fungal infection. Rhino-cerebral and pulmonary involvement are the most common forms and usually occur in immunecompromised patients. Gastrointestinal involvement is extremely rare, the stomach being the most frequently involved site among them. We report a case of gastric mucormycosis in a 37 year old male alcoholic with gastric ulcer. On histological examination, characteristic findings of hyphae with irregular width and right angle branchings were observed in the gastric mucosa and ulcer debris. The diagnosis of gastric mucormycosis was made by the characteristic histological nature. The patient was treated aggressively with antibiotics and antiulcer regimen for 6 weeks, and then no fungus was present on follow up biopsy of gastric mucosa.
Adult ; Alcoholics ; Anti-Bacterial Agents ; Biopsy ; Diagnosis ; Follow-Up Studies ; Fungi ; Gastric Mucosa ; Humans ; Hyphae ; Male ; Mucormycosis* ; Stomach ; Stomach Ulcer* ; Ulcer

BACKGROUND: Pulmonary sequestration is not common and it's diagnosis needs special care such as an aortogram ar tomography. MATERIAL AND METHOD: We have experienced 13 patients who had pulmonary sequestration from January 1990 to September 1997. RESULT: Six men and seven women were treated and their mean age was 25.8+/-14.3 years. Their chief complaints were coughing, chest pain, and no symptoms in decreasing order. There were nine intralobar (ILS) and three extralobar (ELS) pulmonary sequestrations and one patient had both. There was no preference in location of either left or right. They were mainly diagnosed by aortography and their feeding arteries commonly originated from the lower thoracic aorta. The patients with ILS were treated by lobectomy and those with ELS by sequestrectomy. CONCLUSION: to treat pulmonary sequestration properhy, aortogram or chest CT is warranted to iidenty the abnormal origin of feeding artery.
Aorta, Thoracic ; Aortography ; Arteries ; Bronchopulmonary Sequestration* ; Chest Pain ; Cough ; Diagnosis ; Female ; Humans ; Male ; Tomography, X-Ray Computed