Background: Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking. Methods: We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC). Results: The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%, P =0.878). Among these patients, seven received salvage allogeneic HSCT; six remained alive. The other seven patients received ATO without HSCT. Five died from disease progression, and two survived and have been in mCR2 since. Conclusion Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

The global outbreak of coronavirus disease 2019 (COVID-19) is still threatening human health, economy, and social life worldwide. As a counteraction for this devastating disease, a number of vaccines are being developed with unprecedented speed combined with new technologies. As COVID-19 vaccines are being developed in the absence of a licensed human coronavirus vaccine, there remain further questions regarding the long-term efficacy and safety of the vaccines, as well as immunological mechanisms in depth. This review article discusses the current status of COVID-19 vaccine development, mainly focusing on antigen design, clinical trials in later stages, and immunological considerations for further study.

Background/Aims: Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by constitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. Methods: In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltuximab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results: On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cycles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treatment of iMCD. Further large multicenter studies are needed to evaluate the clinical outcomes and adverse events associated with siltuximab.

PURPOSE: The purpose of this study was to assess the current management status of patients with urological issues and to examine the level of knowledge and practice behaviors regarding urinary incontinence (UI) among Korean healthcare providers in long-term care hospitals. METHODS: This study used a cross-sectional descriptive design with a written questionnaire to assess knowledge and practice behaviors of 756 healthcare providers in 11 long-term care hospitals in Korean metropolitan areas. RESULTS: A total 42.6% of participants reported that more than 50% of patients had urologic issues, and that 68.1% of patients were regularly sent to urologists; no participants reported an on-site urologist in their facility. Participants identified collaboration with other hospitals and regular consultations by urologists as important factors in improving urologic care. Although the overall UI knowledge score was upper intermediate, a knowledge deficit was found for risk factors of UI. The knowledge level of physicians was significantly higher than that of other healthcare providers. Practice behaviors of nurses seemed to be better than those of other healthcare providers. CONCLUSIONS: Systematic collaboration between healthcare providers and urologic specialists, enhancing staff competence, and patient-tailored intervention should be recommended to improve quality of care for patients with urologic issues in long-term care hospitals.
Cooperative Behavior ; Delivery of Health Care* ; Health Personnel* ; Humans ; Long-Term Care* ; Mental Competency ; Professional Practice ; Referral and Consultation ; Risk Factors ; Specialization ; Urinary Incontinence*

PURPOSE: Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. METHODS: To induce amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once per day for 14 days. A step-down avoidance test for short-term memory was conducted. AChE histochemistry, immunohistochemistry for collagen IV, and doublecortin were performed. RESULTS: Short-term memory deteriorated in the mice with scopolamine-induced amnesia, concomitant with enhanced AChE expression and suppression of angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short-term memory impairment, suppressed AChE expression, and enhanced angiogenesis in the mice with scopolamine-induced amnesia. CONCLUSIONS: Overexpression of AChE is implicated in both brain and renal disease. The findings of our study indicate that treadmill exercise may be of therapeutic value in neurodegenerative and renal diseases by suppressing the effects of AChE expression.
Acetylcholinesterase ; Amnesia* ; Animals ; Brain ; Brain Injuries ; Collagen ; Exercise Test ; Hippocampus ; Immunohistochemistry ; Learning ; Memory ; Memory, Short-Term* ; Mice ; Rats* ; Scopolamine Hydrobromide

PURPOSE: Prenatal environmental conditions affect the development of the fetus. In the present study, we investigated the effects of exposure to music and noise during pregnancy on neurogenesis and thickness in the motor and somatosensory cortex of rat pups. METHODS: The pregnant rats in the music-applied group were exposed to 65 dB of comfortable music for 1 hour, once per day, from the 15th day of pregnancy until delivery. The pregnant rats in the noise-applied group were exposed to 95 dB of sound from a supersonic sound machine for 1 hour, once per day, from the 15th day of pregnancy until delivery. After birth, the offspring were left undisturbed together with their mother. The rat pups were sacrificed at 21 days after birth. RESULTS: Exposure to music during pregnancy increased neurogenesis in the motor and somatosensory cortex of rat pups. In contrast, rat pups exposed to noise during pregnancy showed decreased neurogenesis and thickness in the motor and somatosensory cortex. CONCLUSIONS: Our study suggests that music and noise during the developmental period are important factors influencing brain development and urogenital disorders.
Animals ; Brain ; Fetus ; Humans ; Mothers ; Motor Cortex ; Music ; Neurogenesis ; Noise ; Parturition ; Pregnancy ; Rats ; Somatosensory Cortex

PURPOSE: Tubeless percutaneous nephrolithotomy (PNL) remains a challenging technique for the surgical treatment of staghorn renal calculi. Our study was designed to compare surgical outcomes between conventional and tubeless PNL. MATERIALS AND METHODS: We retrospectively enrolled consecutive patients who underwent conventional or tubeless PNL under general anesthesia performed by a single surgeon (H.J.) for the treatment of staghorn calculi between 2003 and 2012. All patients were divided into two groups: group 1 included patients who underwent conventional PNL and group 2 included patients who were managed by tubeless PNL for the treatment of staghorn calculi. Preoperative and postoperative parameters were analyzed between the two groups, including age, stone burden, complications, any interventions, and duration of hospital stay. RESULTS: A total of 165 patients (group 1, 106; group 2, 59) were enrolled in the study. No significant differences in age, sex, body mass index, or stone laterality were observed between the two groups. The mean stone burdens (+/-standard deviation) of group 1 and group 2 were 633.6 (+/-667.4) and 529.9 (+/-362.8), respectively (p=0.271). The postoperative stone-free clearance rate was higher in group 2 (78.0%) than in group 1 (69.8%); however, the difference was not clinically significant (p=0.127). In addition, no significant differences in postoperative complications, including fever, bleeding, infection, or additional interventions, were observed between the two groups. CONCLUSIONS: Our results demonstrated that tubeless PNL has the same effectiveness and safety as conventional PNL in the treatment of staghorn calculi. Tubeless PNL may be feasible for managing renal staghorn calculi.
Anesthesia, General ; Body Mass Index ; Calculi ; Fever ; Hemorrhage ; Humans ; Kidney Calculi ; Nephrostomy, Percutaneous ; Postoperative Complications ; Retrospective Studies

PURPOSE: The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, alpha1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats. METHODS: Adult female Sprague-Dawley rats, weighing 250+/-10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted. RESULTS: Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment. CONCLUSIONS: Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.
Adult ; Animals ; Blood-Brain Barrier ; Blotting, Western ; Contracts ; Cyclophosphamide ; Female ; Humans ; Immunohistochemistry ; Injections, Intraperitoneal ; NAD ; Neurons ; Nitric Oxide Synthase ; Nocturia ; Prostatic Hyperplasia ; Rats ; Rats, Sprague-Dawley ; Sulfonamides ; Urinary Bladder ; Urinary Bladder, Overactive

PURPOSE: Stress urinary incontinence (SUI) commonly occurs in women, and it causes enormous impact on quality of life. Surgery, drugs, and exercise have been recommended for the treatment of this disease. Among these exercise is also known to be effective for relieving thesymptoms of SUI, however, the efficacy and underlying mechanisms of exercise on SUI are poorly understood. In the present study, we investigated the effect of treadmill exercise on abdominal leak-point pressure and neuronal activity in the medial preoptic nucleus (MPA), ventrolateral periaqueductal gray (vlPAG), and pontine micturition center (PMC) following urethrolysis in rats. MATERIALS AND METHODS: Adult female Sprague-Dawley rats, weighing 250+/-10 g (9 weeks old), were used in this study. After having undergone transabdominal urethrolysis to induce SUI, the rats were divided into three groups (n=6 in each group): a sham operation group, an SUI-induced group, and an SUI-induced and treadmill exercise group. The rats in the exercise group performed treadmill running for 30 min once a day starting 2 weeks after the induction of SUI and continuing for 4 weeks after surgery. For this study, determination of abdominal leak point pressure and immunohistochemistry for c-Fos in the brain were performed. RESULTS: Induction of transabdominal urethrolysis significantly reduced the abdominal leak point pressure, thereby contributing to the induction of SUI. In contrast, abdominal leak point pressure was significantly improved by treadmill exercise. The expression of c-Fosin the MPA, vlPAG, and PMC, the brain areas relating to micturition, was enhanced by the induction of SUI, whereas treadmill exercise significantly suppressed SUI-induced c-Fos expression, suggesting that neuronal activation in the micturition centers was suppressed by treadmill exercise. CONCLUSION: The present results suggest that treadmill exercise may be an effective therapeutic modality for ameliorating the symptoms of SUI.
Adult ; Animals ; Brain ; Exercise Test ; Female ; Humans ; Immunohistochemistry ; Neurons ; Periaqueductal Gray ; Quality of Life ; Rats ; Rats, Sprague-Dawley ; Running ; Salicylamides ; Urinary Incontinence ; Urination

PURPOSE: Oxytocin is associated with the ability to form normal social attachments. c-Fos is an immediate early gene whose expression is used as a marker for stimulus-induced changes in neurons. The effect of phosphodiesterase-5 (PDE-5) inhibitors on oxytocin activation in the brain without sexual stimuli has not yet been reported. In the present study, we investigated the effects of vardenafil on oxytocin and c-Fos expression in the paraventricular nucleus (PVN) of conscious rats. METHODS: Male Sprague-Dawley rats weighing 300+/-10 g were divided into 6 groups (n=5 in each group): the control group, the 1-day-0.5 mg/kg, the 1-day-1 mg/kg, the 1-day-2 mg/kg, the 3-day-1 mg/kg, and the 7-day-1 mg/kg vardenafil administration group. The experiment was conducted without sexual stimulation. Vardenafil was orally administered. The animals in the control group received an equivalent amount of distilled water orally. The expression of oxytocin and c-Fos in the PVN was detected by immunohistochemistry. RESULTS: Oxytocin expression in the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil appeared in a duration-dependent manner. c-Fos in the oxytocin neurons of the PVN was increased by 1 day administration of 2 mg/kg vardenafil, and this effect of vardenafil also appeared in a duration-dependent manner. These results showed that vardenafil augments the expression of oxytocin with activation of oxytocin neurons in the PVN. CONCLUSIONS: In this study, we showed that the PDE-5 inhibitor, vardenafil directly enhances oxytocin expression and also activates oxytocin neurons in the PVN, which indicates that vardenafil may exert positive effects on affiliation behavior and social interaction.
Animals ; Brain ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Humans ; Imidazoles ; Interpersonal Relations ; Male ; Neurons ; Oxytocin ; Paraventricular Hypothalamic Nucleus ; Piperazines ; Rats ; Rats, Sprague-Dawley ; Sulfones ; Triazines ; Water ; Vardenafil Dihydrochloride