Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia

Background/Aims@#Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. @*Methods@#This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). @*Results@#The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. @*Conclusions@#Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

Neutrophil to Lymphocyte Ratio after Treatment Completion as a Potential Predictor of Survival in Patients with Triple-Negative Breast Cancer / 한국유방암학회지

Purpose@#Triple-negative breast cancer (TNBC) has been associated with worse prognosis, and biomarkers are needed to identify high-risk patients who may benefit from clinical trials or escalated treatment after completion of standard treatment. We aimed to assess whether the post-treatment neutrophil-to-lymphocyte ratio (NLR) can reflect patient prognosis and determine the follow-up period that can provide the most feasible data. @*Methods@#In this retrospective analysis involving patients with TNBC, clinicopathological data, including those on peripheral complete blood cell count, were collected. The prognostic powers of serial NLRs obtained at baseline and after treatment completion were compared. Kaplan-Meier curves were generated to compare the overall survival (OS) and distant disease-free survival (DDFS). @*Results@#In total, 210 patients were enrolled. Forty-three (20.5%) events were detected. Twothirds of the events (29/43) were related to breast cancer. Most recurrent breast cancer-related diseases (27/29) were detected within 5 years of the initial diagnosis. In contrast, half of the events due to secondary malignancies or non-breast-related diseases (7/14) occurred 5 years after the initial diagnosis. Comparison of the prognostic performance of NLRs at baseline and at 6, 12, and 24 months after treatment completion revealed the strongest prognostic performance at 6 months after treatment completion (area under the curve = 0.745). The high NLR group (NLR >2.47) showed worse OS (p = 0.006) and DDFS (p < 0.001) than low NLR group. @*Conclusion@#Elevated post-treatment NLR was significantly associated with worse survival in patients with TNBC. We believe that it can be a useful surrogate marker for identifying highrisk patients with TNBC.

Unusual Lower Back Pain on the Non-Articulated Side in Patient with Bertolotti’s Syndrome

Bertolotti’s syndrome (BS) refers to chronic low back pain (LBP) associated with lumbosacral transitional vertebrae (LSTV). Many studies suggest that the anomalous articulation alters biomechanics, resulting in discomfort on the ipsilateral side. Herein, we present an unusual case of BS presenting pain on the non-articulated side. A 46-year-old man visited our clinic with history of chronic LBP, refractory to treatment of analgesics, modalities and manual therapies. Electrodiagnostic studies showed no evidence of lumbosacral radiculopathy. Radiographies noted unilateral pseudoarticulation of L5∼S1 vertebrae, on the contralateral side of his pain. The pain improved dramatically after sacroiliac joint block and facet joint block with iliolumbar ligament infiltration on the non-articulated side. Clinicians should be cautious that the unaffected joint in BS may serve an important role in altered lumbopelvic biomechanism, since it might eventually lead to intractable chronic LBP when overlooked.

Unusual Lower Back Pain on the Non-Articulated Side in Patient with Bertolotti’s Syndrome

Bertolotti’s syndrome (BS) refers to chronic low back pain (LBP) associated with lumbosacral transitional vertebrae (LSTV). Many studies suggest that the anomalous articulation alters biomechanics, resulting in discomfort on the ipsilateral side. Herein, we present an unusual case of BS presenting pain on the non-articulated side. A 46-year-old man visited our clinic with history of chronic LBP, refractory to treatment of analgesics, modalities and manual therapies. Electrodiagnostic studies showed no evidence of lumbosacral radiculopathy. Radiographies noted unilateral pseudoarticulation of L5∼S1 vertebrae, on the contralateral side of his pain. The pain improved dramatically after sacroiliac joint block and facet joint block with iliolumbar ligament infiltration on the non-articulated side. Clinicians should be cautious that the unaffected joint in BS may serve an important role in altered lumbopelvic biomechanism, since it might eventually lead to intractable chronic LBP when overlooked.

All-Trans Retinoic Acid Synergizes with Enasidenib to Induce Differentiation of IDH2-Mutant Acute Myeloid Leukemia Cells

Purpose@#Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study,the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. Materials and Methods: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination. @*Results@#Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment. @*Conclusion@#Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.

Pontine Necrosis Related with Radiation Therapy, Complicated with Spontaneous Hemorrhage

The brain necrosis induced by radiation therapy (RT) is an uncommon pathology of brain. A case of spontaneous hemorrhage at necrotic brain is also rare. A 52-year-old man who had nasopharyngeal carcinoma and had been treated with RT, presented with gait disturbance, dizziness, ataxia, dysarthria, and dysphagia. Magnetic resonance imaging (MRI) demonstrated progressed radiation necrosis of pons, and spontaneous hemorrhage at the site of necrosis. The hematoma was diminished by conservative treatment. However, the patient’s neurologic symptoms did not recover. Two years later, spontaneous bleeding recurred at necrotic brain. His neurologic symptoms worsened. One year later, his neurologic symptoms were more progressed. He showed severe dysphagia, profound weakness and respiratory failure. This case provides the description of relapsed spontaneous hemorrhage and medullary dysfunction caused by pontine necrosis and progressed post-radiation injury, complicated with hemorrhage, and urges caution in that the necrotic brain tissue may be vulnerable to bleeding.

Lumbar Scoliosis in Patients With Breast Cancer: Prevalence and Relationship With Breast Cancer Treatment, Age, Bone Mineral Density, and Body Mass Index

OBJECTIVE: To identify the prevalence of lumbar scoliosis in breast cancer patients and to investigate the potential risk factors of lumbar scoliosis. METHODS: A retrospective chart review was performed in breast cancer patients aged more than 40 years who underwent dual energy X-ray absorptiometry (DEXA) scanning between January 2014 and December 2014. We divided the patients into control and experimental groups in order to investigate the influence of breast cancer treatment. The curvature of the lumbar spine was measured by using the Cobb method on a DEXA scan. Scoliosis was defined by the presence of a curvature 10° or larger. The variables, including age, bone mineral density (BMD), body mass index (BMI), and breast cancer treatments, were also obtained from the medical chart. Prevalence of lumbar scoliosis was evaluated, and it was compared between the two groups. The relationships between lumbar scoliosis and these variables were also investigated. RESULTS: Lumbar scoliosis was present in 16 out of our 652 breast cancer patients. There was no difference in the prevalence of lumbar scoliosis between the control group (7/316) and the experimental group (9/336) (p=0.70). According to the logistic regression analysis, lumbar scoliosis had no significant association with operation, chemotherapy, hormone therapy, BMI, and BMD (p>0.05). However, age showed a significant relationship with prevalence of lumbar scoliosis (p<0.001; odds ratio, 1.11; 95% confidence interval, 1.054–1.170). CONCLUSION: Prevalence of lumbar scoliosis in patients with breast cancer was 2.45%. Lumbar scoliosis had no association with breast cancer treatments, BMD, and BMI. Age was the only factor related to the prevalence of lumbar scoliosis.

Progressive Bilateral Facial Palsy as a Manifestation of Granulomatosis With Polyangiitis: A Case Report

Bilateral facial palsy, which is usually combined with other diseases, occurs infrequently. It may imply a life-threatening condition. Therefore, the differential diagnosis of bilateral facial palsy is important. However, the etiology is variable, which makes diagnosis challenging. We report a rare case of progressive bilateral facial palsy as a manifestation of granulomatosis with polyangiitis (GPA). A 40-year-old male with otitis media and right facial palsy was referred for electroneurography (ENoG), which showed a 7.7% ENoG. Left facial palsy occurred after 2 weeks, and multiple cavitary opacities were noted on chest images. GPA was diagnosed by lung biopsy. His symptoms deteriorated and mononeuropathy multiplex developed. The possibility of systemic disease, such as GPA, should be considered in patients presenting with bilateral facial palsy, the differential diagnosis of which is summarized in this report.

Risk Factors for Surgical Procedure on Ileo-Colic Intussusception in Children / 소아외과

PURPOSE: The aim of this study was to analyze of the risk factors for surgical procedure on ileo-colic intussusception without leading point in children. METHODS: We retrospectively reviewed medical records of patient treated for ileo-colic intussusception between January 2003 and December 2014. We exclude the patients who had leading point. Because of the large difference on patient's numbers between non-operative group (cases of ileo-colic intussusceptions successfully reduced by air reduction) and operative group (cases underwent operation due to failed air reduction), we compared the data of operative group of patients without leading point between 2003 and 2014 with the data of non-operative group as control group from 2013 to 2014. Clinical features such as gender, age, body temperature, body weight in diagnosis, growth curves for age-gender-body weight, and laboratory data of blood test were compared. RESULTS: In non-operative group, total 94 patients who were treated successfully by the non-operative air reduction. In operative group, total 21 patients treated by surgical procedure. The age under 12 months, weight over upper 75 percentile group, increased segment neutrophil count, decreased hemoglobin level and lymphocyte count were significantly associated with a requirement for surgical procedure. CONCLUSION: We conclude that younger age, higher weight percentile group, increased segment neutrophil, decreased hemoglobin and lymphocyte are the independent risk factors related to operative treatment for ileo-colic intussusception in children. If primary air reduction is failed in patients with such risk factors, operative treatment over ultrasonography or secondary reduction can prevent unnecessary effort and complications, thus emphasizing the consideration of operative treatment when selecting treatment methods.

Accuracy of Needle Placement in Cadavers: Non-Guided Versus Ultrasound-Guided

OBJECTIVE: To compare the accuracy rates of non-guided vs. ultrasound-guided needle placement in four lower limb muscles (tibialis posterior, peroneus longus, and short and long heads of the biceps femoris). METHODS: Two electromyographers examined the four muscles in each of eight lower limbs from four fresh frozen cadavers. Each electromyographer injected an assigned dye into each targeted muscle in a lower limb twice (once without guidance, another under ultrasound guidance). Therefore, four injections were done in each muscle of one lower limb. All injections were performed by two electromyographers using 18 gauge 1.5 inch or 24 gauge 2.4 inch needles to place 0.5 mL of colored acryl solution into the target muscles. The third person was blinded to the injection technique and dissected the lower limbs and determined injection accuracy. RESULTS: A 71.9% accuracy rate was achieved by blind needle placement vs. 96.9% accuracy with ultrasound-guided needle placement (p=0.001). Blind needle placement accuracy ranged from 50% to 93.8%. CONCLUSION: Ultrasound guidance produced superior accuracy compared with that of blind needle placement in most muscles. Clinicians should consider ultrasound guidance to optimize needle placement in these muscles, particularly the tibialis posterior.

Rhabdomyolysis in Acute Spinal Cord Injury Presenting With Nausea and Vomiting as Chief Complaints: A Case Report

Dealing with complications is crucial in the management of patients with spinal cord injury (SCI). We describe a case of rhabdomyolysis in SCI without apparent soft tissue injury, presenting with nausea and vomiting as chief complaints. Given that gastrointestinal discomfort is common in SCI, this case highlights the need to consider rhabdomyolysis as a potential cause of unexplained nausea and vomiting in SCI, and indicate the value of regular check-up of creatine kinase level in SCI patients. Early diagnosis and treatment can prevent acute renal failure that can occur with rhabdomyolysis and minimize the potential threat of declined renal function in SCI patients.

Factors Related to Standing Balance in Patients With Knee Osteoarthritis

OBJECTIVE: To assess factors related to standing balance in patients with knee osteoarthritis (OA). METHODS: In total, 37 female patients with painful knee OA were included. Pain, knee alignment, and Kellgren and Lawrence grade were evaluated accordingly. Static standing balance was measured with a force-platform system under two different conditions: static standing with eyes open (EO) and eyes closed (EC) for 30 seconds. The mean speed (mm/s) of movement of the center of pressure in the anteroposterior (AP) and mediolateral directions and the mean velocity moment (mm2/s) were analyzed for assessment of static balance. RESULTS: In the univariate regression analysis, age and knee alignment showed statistically significant relationships with the mean speed in the AP directions with EO. In the multiple linear regression model, age and knee alignment were positively associated and disease severity was negatively associated with mean speed in the AP directions with EO. However, the variables for EC static measurements were not significantly correlated with age, pain, knee alignment, or radiographic severity (p>0.05). CONCLUSION: These findings show that the worse balance was associated with advanced age, less varus knee malalignment, and mild radiographic changes. Pain was not associated with standing balance.

Postpartum Sacral Stress Fracture Mimicking Lumbar Radiculopathy in a Patient With Pregnancy-Associated Osteoporosis

Postpartum sacral fracture is relatively rare, and its diagnosis is often delayed. We herein report such a case of a 28-year-old patient who presented with an insidious-onset lower back pain, left buttock pain, and radicular symptoms mimicking lumbar radiculopathy. Laboratory tests showed a decreased 25-hydroxy vitamin D level, and the bone mineral densitometry of both femurs was below the expected range. Plain radiographs of the lumbar spine and pelvis showed no definite abnormality, but lumbosacral spinal magnetic resonance imaging identified a left sacral fracture. Symptoms were alleviated with rest and oral analgesic treatment.

The Assessment of Pulmonary Function in Dental Technicians / 대한산업의학회지

OBJECTIVES: Dental technicians are exposed to various toxic materials in the workplace. The objectives of this study were to assess the pulmonary function of dental technicians and to evaluate the association between work-related factors and pulmonary function of dental technicians. METHODS: Study subjects were 209 dental technicians in the Korean Dental Technologist Association. A self-report questionnaire including general characteristics, respiratory symptoms, and work-related characteristics was conducted on study subjects, and a pulmonary function test (PFT) was done. Study subjects were classified into two groups(normal and abnormal pulmonary function) based on the pulmonary function test (PFT). RESULTS: 43 subjects (20.6%) among 209 subjects had abnormal pulmonary function. After adjusting for general characteristics such as age, sex, past medical history, familial history, and smoking status, the odds ratio for work duration (per year) was 1.42(95% confidence interval (CI) 1.14~1.83). After adjusting for general and work-related characteristics, the odds ratio for work duration (per year) was 1.48(95% CI 1.18~1.92). CONCLUSIONS: Dental technicians are exposed to hazardous materials, which might lead to abnormal pulmonary function. A long work duration could increase exposure time, thereby increasing the chance for abnormal pulmonary function. Therefore, pulmonary function tests should be carried out periodically in dental technicians to ensure their pulmonary health.

Multiple Jejunal Myeloid Sarcomas Presenting with Intestinal Obstruction in a Non-leukemic Patient: A Case Report with Ultrastructural Observations

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.

Ischemic Stroke in Rats Enhances Bone Resorption in Vitro

We hypothesized that the formation and differentialtion of osteoclasts are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow in the early stage of stroke. We randomly divided white female Sprague-Dawley (SD) rats (n = 30) into two groups, stroke (n = 15) and sham group (n = 15). On the 7th day after stroke, after cutting away the epiphyses of the femurs and tibias, diaphyseal channels were flushed using alpha-minimum essential medium (alpha-MEM) and bone marrow cells were collected. Bone marrow stem cells, which were extracted from the femur and tibia, were cultured on the 7th day after middle cerebral artery occlusion. We then estimated the ratio of non-adherent cells to total bone marrow cells that included osteoclast precursor cells. After culturing these cells separately, cells that tested positive on the tartrate resistant acid phosphatase (TRAP) were counted and bone resorption was evaluated by using the OAAS(TM) plate. In comparison to the control group, the stroke group showed a higher increase of non-adherent cells in the hemiplegic side bone marrow. In addition, after the primary culture, the stroke group showed an increased number of TRAP positive cells and a higher degree of bone resorption estimated by OAAS(TM) plate. As a result, osteoclastogenesis and osteoclast differentiation are accelerated and the potential of bone resorption is increased in the hemiplegic bone marrow and these changes are detected as early as within the first week after middle cerebral artery occlusion in SD rats.

Saphenous Mononeuropathy after Repetitive Compression on the Knee in a Ballerina: A Case Report

Saphenous mononeuropathy is an uncommon neuropathy in clinical condition, which may incur from various surgical procedures, direct trauma, or entrapment, and most frequently involves at the adductor canal, or Hunter's canal. A 17-year old female, who was majoring in ballet, visited our rehabilitation clinic for numbness in the medial aspect of the left lower leg for the previous 9 months, without weakness. The electrodiagnostic study revealed only a delayed small potential in the left saphenous nerve. MRI examination showed soft tissue swelling in the medial side of the left knee. Accordingly, we diagnosed the patient with saphenous mononeuropathy around the knee, without lumbar plexopathy or femoral neuropathy. We report a case of saphenous mononeuropathy which developed after repetitive compression on the medial side of the knee without any other iatrogenic injury, and include a review of the relevant literature.

Membranoproliferative Glomerulonephritis Associated with Papillary Thyroid Carcinoma / 대한신장학회지

Malignant tumors have been shown to be a major secondary cause of nephrotic syndrome. They have been associated with different glomerulopathy depending on their type. Membranoproliferative glomerulonephritis (MPGN) rarely develops in solid tumors, although cases have been reported in renal cell cancer, melanoma, lung cancer, and tumors in the urogenital system. However, to our knowledge, there have been no case reported of MPGN associated with thyroid cancer. In the present case, we observed MPGN associated with thyroid cancer in a 44-year-old woman with nephrotic syndrome and renal insufficiency. Her thyroid ultrasound revealed a tumor measuring 1.01x1.14x1.48 cm with an indistinct border that was partially calcified. The tumor was confirmed to be papillary carcinoma by percutaneous needle aspiration biopsy. Renal biopsy showed chronic tubulointerstitial nephritis and MPGN. On day 45 of admission, total thyroidectomy and neck lymphadenectomy were performed. After total thyroidectomy, serum total protein, albumin, C3, and C4 normalized. In conclusion, this case represents the first report of simultaneous development of MPGN and thyroid cancer.

Clinical Manifestations of Childhood Intussusception with Ubiquitous Ultrasonography: Comparison with Small Bowel and Ileocecal Type

We analyzed the clinical characteristics and outcome of ileocecal and small bowel intussusceptions (ICI and SBI) in the pediatric patients. From August 2003 to July 2010, 144 children with intussusception were included in this study. We retrospectively reviewed the clinical records and imaging study findings. A total of 86 children with ICI and 58 children with SBI were diagnosed. Children with SBI were older than ICI (36.6+/-24.6 months vs. 24.2+/-21.6 months, p=0.002). Typical symptoms such as irritability, abdominal mass, bloody stool were more frequent in ICI than SBI (p<0.05) patients. In the ICI group, intussusceptums were reduced with air reduction (84.5%), surgery (17.4%), and spontaneity (1.2%). All patients in the SBI group were reduced spontaneously. SBI occurred in older age and was reduced spontaneously more frequently than ICI. Conservative management with close observation with follow-up by ultrasonography is recommended for SBI.

Gasless Laparoscopic Assisted Transumbilical Appendectomy / 대한내시경복강경외과학회지

PURPOSE: This study evaluated the safety and feasibility of gasless laparoscopic assisted transumbilical appendectomy (GLATUA). METHODS: Data for 62 GLATUA and 84 laparoscopic appendectomies (LA) for uncomplicated appendicitis, which had been performed over a 12 month period in a single institution, were compared retrospectively. The GLATUAs were carried out through an umbilical incision. The abdominal wall was retracted upward using an "L"-shaped retractor and the inflamed appendix was found by gasless laparoscopic vision. A transumbilical extracorporeal appendectomy was then performed. The LAs were performed using a three-port system. RESULTS: The GLATUA group had a shorter mean operative time (44.1+/-22.1 vs. 51.5+/-24.7 min, p=0.06), mean time for resuming a soft diet (29.0+/-9.2 vs. 41.3+/-20.7 hrs, p<0.01) and hospital stay (3.0+/-0.9 vs. 3.6+/-1.7, p<0.01) than the LA group. There was no significant difference in complication rates (6.5% vs. 3.6%, p=0.44). The mean medical costs of the GLATUA group were 66.7% of the LA group. CONCLUSION: GLATUA is a safe, feasible and more cost-effective alternative technique for surgery in uncomplicated acute appendicitis than LA.