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Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.
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Background/Aims@#We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. @*Methods@#A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis − VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). @*Results@#The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). @*Conclusions@#This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.
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Multiple myeloma (MM) is a malignant plasma cell neoplasm characterized by anemia, renal failure, hypercalcemia, and osteolytic bone lesions. Although it is a complex and challenging disease, recent advances in treatment options have improved outcomes for patients with MM. In this review, we will discuss the recent treatment strategies for MM and introduce emerging agents.Current Concepts: One breakthrough in the field of MM has been the development of proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. These agents have been shown to markedly improve survival in patients with MM. Furthermore, high-dose chemotherapy with autologous stem cell transplantation remains important in the treatment of transplant-eligible patients. More recently, new immunotherapies such as chimeric antigen receptor (CAR) T-cell therapy or bispecific monoclonal antibodies and agents with new mechanisms of action, have shown promise in the treatment of MM, particularly in patients with relapsed or refractory MM. The recent advancements in MM treatment have greatly improved patient outcomes and offer hope for a cure.Discussion and Conclusion: MM remains an incurable blood cancer owing to repeated relapses. However, the development of CAR T-cell therapies and double-antibody therapies has resulted in remarkable effects in recent clinical trials. Furthermore, combination therapies based on these agents have emerged, and the effectiveness of these agents and combination therapies in the early stages of the disease is being assessed in various clinical trials. Therefore, a cure for MM may soon be possible if the results of these clinical trials are reported and adopted into practice.
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Purpose@#A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. @*Materials and Methods@#In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. @*Results@#At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed. @*Conclusion@#These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).
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Background@#In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. @*Methods@#A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. @*Results@#A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). @*Conclusion@#This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.
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Tofacitinib is an oral, small-molecule Janus kinase inhibitor approved in South Korea for the treatment of moderate to severe ulcerative colitis (UC) on May 1, 2019. However, safety data are lacking. We investigated the incidence of serious adverse events (SAEs) in patients with UC using tofacitinib from the National Health Insurance Service database. In all, 1,026 UC patients were enrolled in this study. The overall incidences (100 person-years; 95% confidence interval) of SAEs were 4.06 (1.63–8.36) and 6.30 (4.59–8.43) in the tofacitinib and anti-TNFi groups, respectively. No thromboembolic event occurred and major cardiovascular events occurred in only three patients (two unstable angina and one congestive heart failure) in the tofacitinib group. The incidence of herpes zoster and tuberculosis did not differ between the two groups. There was no difference in the overall incidence of SAEs, including thromboembolic events, between tofacitinib- and TNFi-treated UC patients.
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Background@#Although survival outcomes of multiple myeloma (MM) have improved with the development of new and effective agents, infection remains the major cause of morbidity and mortality. Here, we evaluated the efficacy of levofloxacin prophylaxis (in a real-world setting) during bortezomib, melphalan, and prednisone (VMP) therapy in elderly patients with newly diagnosed MM. @*Methods@#This study retrospectively analyzed the records of patients with newly diagnosed MM treated with the VMP regimen between February 2011 and September 2020 at three institutes of the Republic of Korea. @*Results@#Of a total of 258 patients, 204 (79.1%) received levofloxacin prophylaxis during VMP therapy. The median number of levofloxacin prophylaxis cycles was 4 (range, 1‒9), but 10 patients did not complete the planned prophylaxis because of side effects. Sixty-six patients (25.5%) experienced severe infections during VMP therapy, most of which (74.7%) occurred within the first four cycles of VMP therapy regardless of levofloxacin prophylaxis status. Early severe infection was significantly associated with poor survival.In multivariate analysis, levofloxacin prophylaxis was significantly associated with a lower risk in early severe infection. @*Conclusion@#Our findings suggest that levofloxacin prophylaxis should be considered at least during the first four cycles of VMP therapy in elderly patients with newly diagnosed MM.
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Plasma cell leukemia (PCL) is a rare and highly aggressive plasma cell neoplasm developing in 0.5‒4% of patients with multiple myeloma (MM). The diagnostic criteria were recently revised from 20% to ≥5% of circulating plasma cells in peripheral blood smears. PCL is classified as primary or secondary; primary PCL is when it presents in patients with no MM. Primary PCL shows clinical and laboratory features at presentation that differ from MM and exhibits a dismal prognosis even with the use of effective agents against MM. Therefore, intensive chemotherapy should be initiated immediately after diagnosis, and autologous stem cell transplantation is recommended for transplant-eligible patients. Maintenance therapy after transplantation may reduce the rate of early relapses. We reviewed the definitions of PCL, revised diagnostic criteria, clinical features, and appropriate initial treatments for primary PCL.
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Background/Aims@#The objective of this study was to evaluate the efficacy and feasibility of the pediatric-inspired regimen of the adult acute lymphoblastic leukemia (ALL) Working Party, the Korean Society of Hematology. @*Methods@#Data of 99 patients with newly diagnosed ALL, who were treated with the KALLA 1406/1407 protocol, were retrospectively analyzed. All patients equally received age-adjusted daunorubicin, vincristine, and prednisolone. L-asparaginase was additionally administered to Philadelphia (Ph)-negative patients according to age, whereas Ph-positive patients received 600 mg/day of imatinib. @*Results@#A total of 99 patients were enrolled in this study, of whom 62 (62.6%) were diagnosed with Ph-negative ALL and 37 (37.3%) were diagnosed with Ph-positive ALL. The median age of patients in the Ph-negative ALL group was 46 years, and that of patients in the Ph-positive ALL group was 49 years. In patients with Ph-negative ALL, 57 (92%) patients achieved complete remission (CR) and CR with incomplete hematologic recovery (CRi). Disease-free survival (DFS) and overall survival (OS) rates at 2 years were estimated to be 42% and 63%, respectively. In patients with Ph-positive ALL, 32 (86%) patients achieved CR/CRi, and 2-year DFS and OS were 31.2% and 49.1%, respectively. Patients who were able to proceed to the allogeneic hematopoietic cell transplantation and younger patients showed significantly superior survival in both Ph-negative ALL and Ph-positive ALL. Neutropenic fever and bacterial infection were the most common and severe adverse events. @*Conclusions@#The KALLA 1406/1407 protocol showed tolerable toxicities in adult ALL patients. Especially, younger patients had more survival benefits with KALLA 1406/1407 protocol.
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We used serial rectal swabs to investigate the amount and duration of virus secretion through the gastrointestinal tract and assessed the association between fecal shedding and gastrointestinal symptoms and to clarify the clinical usefulness testing rectal swabs.We enrolled ten adult patients hospitalized with symptomatic coronavirus disease 2019 (COVID-19). Respiratory and stool specimens were collected by physicians. The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed using real-time reverse-transcription polymerase chain reaction. All ten patients had respiratory symptoms, six had diarrhea, and seven were positive for SARS-CoV-2 on rectal swabs. The viral loads in the respiratory specimens was higher than those in the rectal specimens, and no rectal specimens were positive after the respiratory specimens became negative. There was no association between gastrointestinal symptoms, pneumonia, severity, and rectal viral load. Rectal swabs may play a role in detecting SARS-CoV-2 in individuals with suspected COVID-19, regardless of gastrointestinal symptoms.
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In 2020, the novel coronavirus disease 2019 (COVID-19) began to spread worldwide and remains an ongoing medical challenge. This case series reports on the clinical features and characteristics of patients with inflammatory bowel disease (IBD) and confirmed COVID-19 infection. From February 2020 to March 2021, nine patients with IBD had confirmed COVID-19 across four hospitals in Korea. The median age at COVID-19 diagnosis was 42 years. Six patients were male, and seven patients had ulcerative colitis (UC). No patients required oxygen therapy, intensive care unit hospitalizations, or died. The most common symptom was fever, and gastrointestinal (GI) symptoms developed as diarrhea in five patients with UC. Oral steroids were used to combat UC aggravation in two patients. In this case series of nine IBD patients diagnosed with COVID-19 in Korea, the clinical presentation was predominately a mild respiratory tract infection. Most patients with UC developed new GI symptoms including diarrhea.
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Combination treatment with hypomethylating agents (HMAs) and venetoclax is being used increasingly in elderly patients with acute myeloid leukemia (AML).Venetoclax with HMAs has been reported to be associated with tumor lysis syndrome (TLS) in AML patients with high leukemic burden. We present a case of an elderly AML patient with low leukemic burden who developed TLS while receiving venetoclax and azacitidine (AZA). A 74-year-old man with newly diagnosed AML with NPM1 mutation received combination therapy with venetoclax and AZA in an outpatient clinic. Within 12 hours after starting venetoclax and AZA, the patient was admitted to the emergency room with fever, general weakness, and laboratory findings consistent with TLS. Based on our results, we recommend monitoring at the start of the treatment with venetoclax and HMAs to prevent and control TLS regardless of the leukemic burden and favorable genetic ris
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Intrauterine devices (IUDs) are widely used for contraception in South Korea. However, several complications of IUDs have been reported, including inflammation, obstruction, perforation, and fistula. IUD perforation is the rarest of these complications but is also severe. Migrated IUDs can be retrieved through endoscopy, laparoscopy, or laparotomy. Presented below is an atypical case of an IUD perforating the sigmoid colon, which could not be removed endoscopically, and was subsequently incompletely removed through laparoscopic surgery. The present case underlines the importance of appropriate diagnosis and treatment approach in the management of IUD perforation.
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Purpose@#A hyperextended knee is described as knee pain associated with an impaired knee extensor mechanism. Additionally, a hyperextended knee may involve reduced position sense of the knee joint that decreases the individual’s ability to control end-range knee extension movement. The purpose of this study was to investigate the effects of visual biofeedback information for plantar pressure distribution on knee joint angle and lower extremity muscle activities in participants with hyperextended knees. @*Methods@#Twenty-three participants with hyperextended knees were recruited for the study. Surface electromyography signals were recorded for the biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior muscle activities. The plantar pressure distribution was displayed and measured using a pressure distribution measuring plate. Knee joint angle kinematic parameters were recorded using a motion analysis system. The visual biofeedback condition was the point at which the difference between the forefoot and backfoot plantar foot pressure on the monitor was minimized. The Wilcoxon signed-rank test was used to determine the significance between the visual biofeedback condition and the preferred condition. @*Results@#The knee joint angle was significantly decreased in the visual biofeedback condition compared to that in the preferred condition (p<0.05). The rectus femoris and gastrocnemius muscle activities were significantly different between the visual biofeedback and preferred conditions (p<0.05). @*Conclusion@#The results of this study showed that visual biofeedback of information about plantar pressure distribution is effective for correcting hyperextended knees.
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Intrauterine devices (IUDs) are widely used for contraception in South Korea. However, several complications of IUDs have been reported, including inflammation, obstruction, perforation, and fistula. IUD perforation is the rarest of these complications but is also severe. Migrated IUDs can be retrieved through endoscopy, laparoscopy, or laparotomy. Presented below is an atypical case of an IUD perforating the sigmoid colon, which could not be removed endoscopically, and was subsequently incompletely removed through laparoscopic surgery. The present case underlines the importance of appropriate diagnosis and treatment approach in the management of IUD perforation.
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Purpose@#A hyperextended knee is described as knee pain associated with an impaired knee extensor mechanism. Additionally, a hyperextended knee may involve reduced position sense of the knee joint that decreases the individual’s ability to control end-range knee extension movement. The purpose of this study was to investigate the effects of visual biofeedback information for plantar pressure distribution on knee joint angle and lower extremity muscle activities in participants with hyperextended knees. @*Methods@#Twenty-three participants with hyperextended knees were recruited for the study. Surface electromyography signals were recorded for the biceps femoris, rectus femoris, gastrocnemius, and tibialis anterior muscle activities. The plantar pressure distribution was displayed and measured using a pressure distribution measuring plate. Knee joint angle kinematic parameters were recorded using a motion analysis system. The visual biofeedback condition was the point at which the difference between the forefoot and backfoot plantar foot pressure on the monitor was minimized. The Wilcoxon signed-rank test was used to determine the significance between the visual biofeedback condition and the preferred condition. @*Results@#The knee joint angle was significantly decreased in the visual biofeedback condition compared to that in the preferred condition (p<0.05). The rectus femoris and gastrocnemius muscle activities were significantly different between the visual biofeedback and preferred conditions (p<0.05). @*Conclusion@#The results of this study showed that visual biofeedback of information about plantar pressure distribution is effective for correcting hyperextended knees.
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Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has become a global pandemic and is now the most threatening public health issue. Patients with the infection present with high fever and pneumonia with respiratory symptoms, but some patients also develop digestive symptoms such as diarrhea, vomiting, and abdominal pain. This may be the basis for the transmission route of the new virus, not only for respiratory infection through droplets but also for fecal-to-oral transmission. In addition, the high expression level of angiotensin-converting enzyme 2 on the surface cells in the gastrointestinal tract may support the occurrence of digestive symptoms and the possibility of fecal-to-oral transmission. Recent studies have shown positive fecal polymerase chain reaction (PCR) test results in patients with the infection who showed digestive symptoms. Therefore, we reviewed the related literature on the occurrence of digestive symptoms in patients with COVID-19 and present the usefulness and clinical application of the fecal PCR test for identifying the potential infection route and criteria for isolation.
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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.
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Background/Aims@#It is difficult to reach a social agreement on the appropriatelevel of compensation for professionals. This study was performed to examine thephysician fee embedded in the relative value unit (RVU) system in comparisonwith the Korean hourly minimum wage. @*Methods@#The Health Insurance Service Price and the Korean Classification ofProcedural Terminology were used to obtain the hourly wages of physicians fordesignated health care services. In addition, the physician fee schedule at theUnited States Centers for Medicare and Medicaid Services and the Organisationfor Economic Co-operation and Development (OECD) report on minimal wagewere used. Health care service fees were selected based on laboratory, pathology,imaging, and procedure codes as well as examination fees. For calculation of physicianlabor costs per hour, physician workload × conversion factor was divided bythe time involved. To calculate the proportion of physician labor fee in the totalfee, the physician workload RVU for each service fee was divided by the total RVU. @*Results@#A total of 27 physician fee codes were selected. Compared to the Koreanhourly minimum wage in 2015, the average physician wages were greater by 2.80-fold for primary care and by 3.05-fold for tertiary care. The mean proportion ofphysician labor cost in the total cost was 0.19, which was significantly lower thanthat of corresponding procedures in the United States RVU (mean, 0.48). @*Conclusions@#The average Korean physician wages compared to the hourly minimumwage were disproportionately low compared to the USA and other referenceOECD countries.
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Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.