Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

4'-Fluorouridine is a broad-spectrum orally efficacious antiviral blocking respiratory syncytial virus and SARS-CoV-2 replication

The COVID-19 pandemic has underscored the critical need for broad-spectrum therapeutics against respiratory viruses. Respiratory syncytial virus (RSV) is a major threat to pediatric patients and the elderly. We describe 4-fluorouridine (4-FlU, EIDD-2749), a ribonucleoside analog that inhibits RSV, related RNA viruses, and SARS-CoV-2 with high selectivity index in cells and well-differentiated human airway epithelia. Polymerase inhibition in in vitro RdRP assays established for RSV and SARS-CoV-2 revealed transcriptional pauses at positions i or i+3/4 post-incorporation. Once-daily oral treatment was highly efficacious at 5 mg/kg in RSV-infected mice or 20 mg/kg in ferrets infected with SARS-CoV-2 WA1/2020 or variant-of-concern (VoC) isolate CA/2020, initiated 24 or 12 hours after infection, respectively. These properties define 4-FlU as a broad-spectrum candidate for the treatment of RSV, SARS-CoV-2 and related RNA virus infections. One-Sentence Summary4-Fluorouridine is an orally available ribonucleoside analog that efficiently treats RSV and SARS-CoV-2 infections in vivo.

The current status of hormone treatment for prostate cancer patients in Korean real-world practice: a multi-institutional observational study / 亚洲男科学杂志(英文版)

We aimed to evaluate the current nationwide trend, efficacy, safety, and quality of life (QoL) profiles of hormone treatment in real-world practice settings for prostate cancer (PCa) patients in Korea. A total of 292 men with any biopsy-proven PCa (TanyNanyMany) from 12 institutions in Korea were included in this multi-institutional, observational study of prospectively collected data. All luteinizing hormone-releasing hormone (LHRH) agonists were allowed to be investigational drugs. Efficacy was defined as (1) the rate of castration (serum testosterone ≤50 ng dl-1) at 4-week visit and (2) breakthrough (serum testosterone >50 ng dl-1 after castration). Safety assessments included routine examinations for potential adverse events, laboratory tests, blood pressure, body weight, and bone mineral density (BMD, at baseline and at the last follow-up visit). QoL was assessed using the Expanded Prostate Cancer Index Composite-26 (EPIC-26). The most common initial therapeutic regimen was LHRH agonist with anti-androgen (78.0%), and the most commonly used LHRH agonist for combination and monotherapy was leuprolide (64.0% for combination and 58.0% for monotherapy). The castration and breakthrough rates were 78.4% and 6.6%, respectively. The laboratory results related to dyslipidemia worsened after 4 weeks of hormone treatment. In addition, the mean BMD T-score was significantly lower at the last follow-up (mean: -1.950) compared to baseline (mean: -0.195). The mean total EPIC-26 score decreased from 84.8 (standard deviation [s.d.]: 12.2) to 78.3 (s.d.: 8.1), with significant deterioration only in the urinary domain (mean: 23.5 at baseline and 21.9 at the 4-week visit). These findings demonstrate the nationwide trend of current practice settings in hormone treatment for PCa in Korea.

Prevalence and molecular characteristics of 16s rRNA methylase gene rmtB in amikacin resistant Escherichia coli isolated from South Korea / 대한수의학회지

The production of rmtB-encoded 16S rRNA methylases has emerged as a novel mechanism promoting high-level resistance toward aminoglycosides in Gram-negative bacteria. Between 2015 and 2017, 636 distinct commensal Escherichia (E.) coli isolates were collected from different farms in South Korea to determine the prevalence and molecular characteristics of rmtB. The positive rates of rmtB between all the isolates and amikacin-resistant isolates were 1.1 and 100%, respectively. High-level aminoglycoside resistance could be transferred by conjugation from rmtB-positive donors to higher amikacin-resistance efficacies. This is the first report of 16S rRNA methylase-encoding genes in E. coli isolated from food-producing animals in Korea.

Generation and protective efficacy of a cold-adapted attenuated genotype 2b porcine epidemic diarrhea virus

The recent emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) underscore the urgent need for the development of novel, safe, and effective vaccines against the prevailing strain. In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. Whole genome sequencing identified 12 amino acid changes in the cold-adapted strain with no insertions and deletions throughout the genome. Animal inoculation experiments confirmed the attenuated phenotype of Aram-P29-CA virus in the natural host. Pregnant sows were orally administered P29-CA live vaccines two doses at 2-week intervals prior to parturition, and the newborn piglets were challenged with the parental virus. The oral homologous prime-boost vaccination of P29-CA significantly improved the survival rate of the piglets and notably mitigated the severity of diarrhea and PEDV fecal shedding after the challenge. Furthermore, strong antibody responses to PEDV were detected in the sera and colostrum of immunized sows and in the sera of their offspring. These results demonstrated that the cold-adapted attenuated virus can be used as a live vaccine in maternal vaccination strategies to provide durable lactogenic immunity and confer passive protection to litters against PEDV.

Phenotypic and genotypic analyses of an attenuated porcine reproductive and respiratory syndrome virus strain after serial passages in cultured porcine alveolar macrophages

The porcine reproductive and respiratory syndrome virus (PRRSV) is a globally ubiquitous swine viral pathogen that causes major economic losses worldwide. We previously reported an over-attenuated phenotype of cell-adapted PRRSV strain CA-2-P100 in vivo. In the present study, CA-2-P100 was serially propagated in cultured porcine alveolar macrophage (PAM) cells for up to 20 passages to obtain the derivative strain CA-2-MP120. Animal inoculation studies revealed that both CA-2-P100 and CA-2-MP120 had decreased virulence, eliciting weight gains, body temperatures, and histopathologic lesions similar to those in the negative control group. However, compared to CA-2-P100 infection, CA-2-MP120 yielded consistently higher viremia kinetics and enhanced antibody responses in pigs. All pigs inoculated with CA-2-MP120 developed viremia and seroconverted to PRRSV. During 20 passages in PAM cells, CA-2-MP120 acquired 15 amino acid changes that were mostly distributed in nsp2 and minor structural protein-coding regions. Among these changes, 6 mutations represented reversions to the sequences of the reference CA-2 and parental CA-2-P20 strains. These genetic drifts may be hypothetical molecular markers associated with PRRSV macrophage tropism and virulence. Our results indicate that the PAM-passaged CA-2-MP120 strain is a potential candidate for developing a live, attenuated PRRSV vaccine.

Evaluation of the efficacy of an attenuated live vaccine based on virulent porcine reproductive and respiratory syndrome virus 2 in young pigs

The efficacy of the CA-2-MP120 vaccine, a cell culture-attenuated strain of virulent porcine reproductive and respiratory syndrome virus (PRRSV), was assessed in pigs. Despite the persistence of viremia in all vaccinated animals during the immunization period, the virus was not detected in vaccinated pigs following challenge. Furthermore, no pigs in the vaccinated group shed PRRSV nasally, orally or rectally throughout the experiment. Moreover, histopathological lung and lymph node lesions in the immunized group were much milder than those in the unimmunized and challenged group. These results indicated that CA-2-MP120 can provide effective protection against virulent wildtype PRRSV-2.

Evaluation of the efficacy of an attenuated live vaccine based on virulent porcine reproductive and respiratory syndrome virus 2 in young pigs / 대한수의학회지

The efficacy of the CA-2-MP120 vaccine, a cell culture-attenuated strain of virulent porcine reproductive and respiratory syndrome virus (PRRSV), was assessed in pigs. Despite the persistence of viremia in all vaccinated animals during the immunization period, the virus was not detected in vaccinated pigs following challenge. Furthermore, no pigs in the vaccinated group shed PRRSV nasally, orally or rectally throughout the experiment. Moreover, histopathological lung and lymph node lesions in the immunized group were much milder than those in the unimmunized and challenged group. These results indicated that CA-2-MP120 can provide effective protection against virulent wildtype PRRSV-2.

Crohn's disease and smoldering multiple myeloma: a case report and literature review

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.

Therapy-related acute promyelocytic leukemia in plasma cell myeloma treated with melphalan: a case report and literature review

No abstract available.

Medication-related osteonecrosis of the jaw: a preliminary retrospective study of 130 patients with multiple myeloma / 대한악안면성형재건외과학회지

BACKGROUND: Multiple myeloma (MM) is characterized by a neoplastic proliferation of plasma cells primarily in the bone marrow. Bisphosphonates (BP) are used as supportive therapy in the management of MM. This study aimed to analyze the incidence, risk factors, and clinical outcomes of medication-related necrosis of the jaw (MRONJ) in MM patients. METHODS: One hundred thirty MM patients who had previous dental evaluations were retrospectively reviewed. Based on several findings, we applied the staging and treatment strategies on MRONJ. We analyzed gender, age, type of BP, incidence, and local etiological factors and assessed the relationship between these factors and the clinical findings at the first oral examination. RESULTS: MRONJ was found in nine male patients (6.9%). The mean patient age was 62.2 years. The median BP administration time was 19 months. Seven patients were treated with a combination of IV zoledronate and pamidronate, and two patients received single-agent therapy. The lesions were predominantly located in the mandible (n = 8), and the most common predisposing dental factor was a history of prior extraction (n = 6). Half of the MRONJ were related to diseases found on the initial dental screen. Patients with MRONJ were treated with infection control and antibiotic therapy. When comparing between the MRONJ stage and each factor (sign, location, etiologic factor, BP type, treatment, and outcome), there were no significant differences between stages, except for between the stage and sign (with or without purulence). CONCLUSIONS: For prevention of MRONJ, we recommend routine dental examinations and treatment prior to starting BP therapy.

Bone Regeneration Using Bilayer Bone Augmentation around Dental Implants: A Preliminary Study by Micro-CT in Dogs

The purpose of this preliminary study was to compare the effects of the bilayer bone augmentation technique (BBA) for the treatment of dehiscence-type defects around implants and evaluate the role as a membrane of the xenogenic bone positioned as the outer layer in the BBA technique using a micro-computed tomography (micro-CT). Four standardized dehiscence defects were prepared on each mandible bilaterally in 3 dogs and 1 implant was placed per defect, where each defect was treated with autograft (AB), xenograft (XB), BBA technique, or negative control without a membrane. Two months post-regenerative surgery, sectioned bone blocks were obtained. The image acquisitions were then scanned by micro-CT. Bone volume (BV), horizontal bone width (HBW) and vertical bone height (VBH) were measured through the analyses program. The BV were 11.08 mm3, 10.42 mm3, 8.1 mm3, and 7.01 mm3 in XB, BBA, control, and AB group in sequence of high value, respectively. HBW were 1.33 mm, 1.3 mm, 1.06 mm, and 1.03 mm in XB, BBA, AB, and control group, respectively. VBH were 4.88 mm, 4.85 mm, 4.74 mm, and 4.67 mm in XB, BBA, AB, and control group, respectively. However, there was no significant difference between the 4 groups. VBH tended to be higher in sequence of control, AB, BBA, and XB group (p for trend <0.05). The results showed the usefulness of the BBA technique involving mechanical support for prolonged space maintenance of xenogenic bone, for the treatment of dehiscence-type defects around implants. However, further studies with a larger sample size are required to confirm the results.

Responses to Overdiagnosis in Thyroid Cancer Screening among Korean Women / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Communicating the harms and benefits of thyroid screening is necessary to help individuals decide on whether or not to undergo thyroid cancer screening. This study was conducted to assess changes in thyroid cancer screening intention in response to receiving information about overdiagnosis and to determine factors with the greatest influence thereon. MATERIALS AND METHODS: Data were acquired from subjects included in the 2013 Korean National Cancer Screening Survey (KNCSS), a nationwide, population-based, cross-sectional survey. Of the 4,100 respondents in the 2013 KNCSS, women were randomly subsampled and an additional face-to-face interview was conducted. Finally, a total of 586 female subjects were included in this study. Intention to undergo thyroid cancer screening was assessed before and after receiving information on overdiagnosis. RESULTS: Prior awareness of overdiagnosis in thyroid cancer screening was 27.8%. The majority of subjects intended to undergo thyroid cancer screening before and after receiving information on overdiagnosis (87% and 74%, respectively). Only a small number of subjects changed their intention to undergo thyroid cancer screening from positive to negative after receiving information on overdiagnosis. Women of higher education level and Medical Aid Program recipients reported being significantly more likely to change their intention to undergo thyroid cancer screening afterreceiving information on overdiagnosis,whilewomen with stronger beliefs on the efficacy of cancer screening were less likely to change their intention. CONCLUSION: Women in Korea appeared to be less concerned about overdiagnosis when deciding whether or not to undergo thyroid cancer screening.

Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement

No abstract available.

Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin-, and Stress-induced Ulcers in Rats / 전남의대학술지

This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80degrees C for 3 min or treatment with 0.01% pepsin at 37degrees C for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.

Cervical Necrotizing Fasciitis Caused by Dental Infection / 대한악안면성형재건외과학회지

Necrotizing fasciitis (NF) is defined as rapidly progressive necrosis of subcutaneous fat and fascia. Although NF of the face is rare, its mortality rate is nearly 30%. It usually originates from dental infection and can lead to involvement of the neck, mediastinum, and chest wall. Complications resulting from pre-existing systemic diseases can increase the mortality rate. Known complication factors for NF include diabetes, malnutrition, advanced age, peripheral vascular disease, renal failure, and obesity. Here, we report a case of NF originating from dental infection in an 88-year-old woman already diagnosed with hypertension, thoracic aortic aneurysm, and renal diseases. Such conditions limited adequate surgical and antibiotic treatment. However, interdisciplinary treatment involving multiple departments was implemented with good results.

Gastroprotective Effects of Glutinous Rice Extract against Ethanol-, Indomethacin-, and Stress-induced Ulcers in Rats / 전남의대학술지

This study was designed to evaluate the efficacy of an orally administered aqueous extract of glutinous rice (GRE) to protect against acute gastric mucosal lesions induced by ethanol, indomethacin, and water immersion restraint stress in rats and to characterize the active substances responsible for the protection. GRE was shown to dose-dependently prevent the gastric lesions induced by the above ulcerogenic treatments at doses of 30 to 300 mg/kg. GRE treatment increased the gastric mucin content and partially blocked the ethanol-induced depletion of the gastric mucus layer. Also, it increased the nonprotein sulfhydryl concentration in the gastric mucosa. The gastroprotective action of GRE was markedly enhanced by co-treatment with 4-8 mg/kg tea extracts. The activity of GRE was completely lost by heat treatment at 80degrees C for 3 min or treatment with 0.01% pepsin at 37degrees C for 1 h. Protein extraction studies indicated that prolamins are involved in the gastroprotective activity of GRE. Our results suggest that glutinous rice proteins are useful for the prevention and treatment of gastritis and peptic ulcer.

Plasma Cell Myeloma Initially Presenting as Lung Cancer

No abstract available.

Change in Electromyographic Activity of Wrist Extensor by Cylindrical Brace

PURPOSE: To verify the effect of a newly-developed cylindrical type forearm brace, which was designed to give focal counterforce perpendicularly on the muscle belly of the wrist extensor. MATERIALS AND METHODS: The dominant hands of 24 (12 males, 12 females) healthy subjects were tested. Two types of forearm braces (focal cylindrical type and broad pneumatic type) were examined. The braces were applied at the extensor carpi radialis brevis, 5 to 7 cm distal to the lateral epicondyle. Two surface electrodes were attached to the proximal and distal parts of the brace. By quantitative electromyography, the mean amplitudes of voluntary extensor carpi radialis brevis contraction before and after applying each brace were recorded and analyzed. RESULTS: The mean amplitudes of the focal cylindrical brace and broad pneumatic brace were reduced significantly compared to no brace (p<0.05), with a larger reduction for the cylindrical brace than the pneumatic brace (p<0.05). There was no significant difference between the proximal and distal mean amplitudes with each brace. CONCLUSION: A cylindrical type brace decreased electromyographic activity in the wrist extensor more effectively than did the pneumatic type brace.