Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): an open-label phase I/II trial.

BACKGROUND: Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). PATIENTS AND METHODS: This phase I/II study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase-α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1000 mg/m2 on days 1 and 8) in 28-day cycles. RESULTS: Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase II evaluation. Twenty-five patients were enrolled in phase II of the study. Frequent grade ≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival was 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma than those with PTCL-not otherwise specified (55.6% versus 15.4%, respectively, P = 0.074) and progression-free survival was significantly longer (13.0 versus 5.1 months, respectively, P = 0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. CONCLUSION: The combination of copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.

Preoperative evaluation of mammographic microcalcifications after neoadjuvant chemotherapy for breast cancer.

AIM: To assess the predictive value of preoperative residual mammographic microcalcifications for residual tumours after neoadjuvant chemotherapy (NAC) for breast cancer. MATERIALS AND METHODS: This single-centre retrospective study included breast cancer patients who underwent NAC and demonstrated suspicious microcalcifications within or near the tumour bed on mammography from June 2015 to August 2018. The residual microcalcifications and remnant lesion on magnetic resonance imaging (MRI) were correlated with histopathological findings of residual tumours and immunohistochemical markers. RESULTS: A total of 96 patients were included. Ten patients achieved pathological complete response (pCR) and previous suspicious microcalcifications were associated with benign pathology in 10.4% (10/96) of the patients. In the remaining 86 patients who did not achieve pCR, 61.5% (59/96) of the residual microcalcifications were associated with invasive or in situ carcinoma and 28.1% (27/96) with benign pathology. Hormone receptor-positive (HR+) patients had the highest proportion of residual malignant microcalcifications compared to HR- patients (48.9% versus 13.5%, respectively; p=0.019). MRI correlated better than residual microcalcifications on mammography in predicting residual tumour extent in all subtypes (ICC=0.709 versus 0.365). MRI also showed higher correlation with residual tumour size for the HR-/HER2+ and HR-/HER2- subtype (ICC=0.925 and 0.876, respectively). CONCLUSION: The extent of microcalcifications on mammography after NAC did not correlate with the extent of residual cancer in 38.5% of women. Regardless of the extent of microcalcifications, residual tumour extent on MRI after NAC and molecular subtype could be an accurate tool in evaluating residual cancer after NAC.

Notch1 inactivation promotes invasion and metastasis of nasopharyngeal carcinoma cells partly through Slug activation.

Nasopharyngeal carcinoma (NPC) is a rare form of the head and neck cancer of the epithelial lining of the nasopharynx and exhibits the highest metastatic rate among head and neck cancers. Underlying mechanisms of metastasis remain largely unknown. Here, we explored whether Notch1 affects the invasion and metastasis of NPC cells. In vitro migration and invasion capacities were evaluated after the knockdown of Notch1 expression in NPC cells. To investigate the role of Notch1 in in vivo metastasis, we examined the metastatic ability to the lungs following administration of cancer cells via mouse tail vein. The expression of epithelial-mesenchymal transition (EMT) markers associated with Notch1-mediated metastasis was investigated, and their roles in metastasis and relationship with Notch1 expression were investigated. Suppression of Notch1 expression increased the ability of NPC cells to invade Matrigel in vitro. Knockdown of Notch1 expression in NPC cells resulted in extensive lung metastasis in a mouse model and increased the mRNA expression of Slug in NPC cells. Slug-specific RNA interference resulted in the loss of the metastatic and invasion capacities in Notch1-suppressed NPC cells. These findings show that Notch1 has a significant suppressive role in the regulation of metastasis in NPCs, suggestive of its prudent use in clinical trials.

The effects of body mass index on the hereditary influences that determine peak bone mass in mother-daughter pairs (KNHANES V).

UNLABELLED: A daughter's bone mineral density (BMD) is significantly correlated with her mother's BMD, but the daughter's body mass index (BMI) could modulate this association. Maternal inheritance dominantly affects daughters with a lower BMI, but BMI could compensate for hereditary influences in daughters with a higher BMI in terms of daughter's BMD. INTRODUCTION: Achieving optimal peak bone mass at a young age is the best way to protect against future osteoporosis and subsequent fractures. Although environmental components influence bone mass accrual, but peak bone mass is largely programmed by inheritance. The aims of this study were to investigate the influence of maternal inheritance on the daughter's bone mass and to assess whether these influences differ according to the daughter's body mass index (BMI). METHODS: We used data obtained from the 2010 Korean National Health and Nutrition Examination Survey V and included 187 mother-daughter pairs. Bone mineral density (BMD) was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) by using dual-energy X-ray absorptiometry (DXA). The daughter group was stratified into two groups according to the mean BMI (21.4 kg/m(2)). RESULTS: The daughters' BMD correlated significantly with both their BMI and their mothers' Z-score for each skeletal site. In the daughters with a lower BMI (≤21.4 kg/m(2)), the BMDs at the FN and TH were affected more by the mothers' Z-score than by the daughters' BMI. Meanwhile, the influence of the daughters' BMI on their BMD was higher than that of their mothers' Z-score in daughters with a higher BMI (>21.4 kg/m(2)). Moreover, the mothers' Z-scores were a significant predictor of their daughters having Z-scores < -1.0 only in daughters with a lower BMI. CONCLUSIONS: This study suggests that maternal inheritance is an important determinant of the daughters' bone mass, but that this hereditary factor may vary according to the daughters' BMI.

Classification by causes of dark circles and appropriate evaluation method of dark circles.

BACKGROUND: Dark circles refer to a symptom that present darkness under the eyes. Because of improvement in the quality of life, the dark circles have been recognized as one of major cosmetic concerns. However, it is not easy to classify the dark circles because they have various causes. METHODS: To select suitable instruments and detailed evaluation items, the dark circles were classified according to the causes through visual assessment, Wood's lamp test, and medical history survey for 100 subjects with dark circles. After the classification, were newly recruited for instrument conformity assessment. Through this, suitable instruments for dark circle evaluation were selected. We performed a randomized clinical trial for dark circles, a placebo-controlled double-blind study, using effective parameters of the instruments selected from the preliminary test. RESULTS: Dark circles of vascular type (35%) and mixed type (54%), a combination of pigmented and vascular types, were the most common. Twenty four subjects with the mixed type dark circles applied the test product (Vitamin C 3%, Vitamin A 0.1%, Vitamin E 0.5%) and placebo on randomized split-face for 8 weeks. The effective parameters (L*, a, M.I., E.I., quasi L*, quasi a* and dermal thickness) were measured during the study period. Result showed that the L* value of Chromameter(®) , Melanin index (M.I.) of Mexameter(®) and quasi L* value obtained by image analysis improved with statistical significance after applying the test product compared with the placebo product. CONCLUSION: We classified the dark circles according to the causes of the dark circles and verified the reliability of the parameter obtained by the instrument conformity assessment used in this study through the efficacy evaluation. Also based on this study, we were to suggest newly established methods which can be applied to the evaluation of efficacy of functional cosmetics for dark circles.

Identification of a novel HLA-B*15 variant, B*15:367, using sequence-based typing in a Korean woman.

New allele, B*15:367, differs from B*15:11:01 by a single nucleotide exchange at codon 222 (GAG→AAG).

Serum 25-hydroxyvitamin D level and the risk of mild cognitive impairment and dementia: the Korean Longitudinal Study on Health and Aging (KLoSHA).

OBJECTIVE: The association of low vitamin D status with mild cognitive impairment (MCI), a preclinical condition that can lead to dementia, has not yet been fully explored. Our aim was to investigate the association between vitamin D status and the future risk of MCI and dementia in older adults. DESIGN, SETTING AND PARTICIPANTS: We conducted a population-based prospective study as a part of the Korean Longitudinal Study on Health and Aging. Four hundred and twelve elderly participants who completed evaluations of cognitive function and metabolic parameters in 2005-2006 and 2010-2011 were analysed. MAJOR OUTCOME MEASURE: The rate of development of MCI or dementia during the study period was compared according to baseline vitamin D status. Binary logistic regression analysis was performed to investigate any independent association between vitamin D status and the risks of MCI or dementia. RESULTS: Among 405 subjects that remained after excluding seven demented subjects at baseline, 338 subjects remained unchanged or improved in their diagnosis for cognitive function during the study period, whereas 67 subjects showed progression to MCI or dementia. When analyzing 236 subjects whose baseline mini-mental state examination (MMSE) scores were <27, severe vitamin D deficiency at baseline, defined as <25 nmol/l, was independently associated with the progression of cognitive impairment. Among 297 subjects who were normal at baseline, 50 acquired MCI and 247 remained normal. Severe vitamin D deficiency was also independently associated with the development of MCI when analyzing 145 subjects whose baseline MMSE scores were <27. CONCLUSION: Severe vitamin D deficiency was independently associated with the future risk of MCI as well as dementia, especially in older adults whose baseline MMSE scores had decreased only modestly.

Favorable effect of dietary vitamin C on bone mineral density in postmenopausal women (KNHANES IV, 2009): discrepancies regarding skeletal sites, age, and vitamin D status.

UNLABELLED: Dietary vitamin C intake showed significant positive associations with BMD in postmenopausal women, especially with vitamin D deficiency. INTRODUCTION: Although there is a positive role of vitamin C in osteoblastogenesis, debate remains about the contribution of vitamin C to bone mineral density (BMD) in humans. METHODS: Data were derived from the Fourth Korean National Health and Nutrition Examination Survey. Dietary information was assessed using a 24-h dietary recall questionnaire. BMD was measured by dual-energy X-ray absorptiometry at the lumbar and hip. RESULTS: A total of 1,196 postmenopausal women aged 50 years and older were stratified into tertiles by daily dietary vitamin C intake. After adjusting for traditional confounders, dietary vitamin C intake tertile was significantly positively associated with BMD at all sites (R = 0.513 for lumbar spine (LS) and R = 0.657 for femoral neck (FN), P < 0.05 for each). The subjects with osteoporosis had significantly lower dietary vitamin C intake than did subjects without osteoporosis (74.4 ± 66.2 vs 94.1 ± 78.6 mg/day for LS and 65.5 ± 56.6 vs 94.3 ± 79.2 mg/day for FN, respectively, P < 0.001). The multiple-adjusted odds ratio for osteoporosis for dietary vitamin C <100 mg/day was 1.790 (95 % CI 1.333-2.405, P < 0.001). However, the significant association between vitamin C intake and BMD was only observed in subjects with vitamin D deficiency and aged 50-59 years or >70 years. CONCLUSION: Dietary vitamin C intake was positively associated with BMD in postmenopausal women, and inadequate vitamin C intake could increase the risk of osteoporosis.

INCB018424 induces apoptotic cell death through the suppression of pJAK1 in human colon cancer cells.

Janus kinase (JAK) is one of the main upstream activators of signal transducers and activators of transcription (STAT) that are constitutively activated in various malignancies and are associated with cell growth, survival, and carcinogenesis. Here, we investigated the role of JAKs in colorectal cancer in order to develop effective therapeutic targets for INCB018424, which is the first JAK1/2 inhibitor to be approved by FDA. After examining the basal expression levels of phospho-JAK1 and phospho-JAK2, we measured the effects of INCB018424 on the phosphorylation of JAK1/2 using western blot analysis. Cell viability was determined using the trypan blue exclusion assay. The cell death mechanism was identified by the activation of caspase 3 using western blot and annexin V staining. The basal levels of phospho-JAK1 and phospho-JAK2 were cancer cell type dependent. Colorectal cancer cell lines that phosphorylate both JAK1 and JAK2 include DLD-1 and RKO. INCB018424 inactivates both JAK1 and JAK2 in DLD-1 cells but inactivates only JAK1 in RKO cells. Cell death was proportional to the inactivation of JAK1 but not JAK2. INCB018424 causes caspase-dependent cell death, which is prevented by treatment with z-VAD. The inhibition of JAK1 phosphorylation seemed sufficient to allow INCB018424-mediated apoptosis. JAK1 is a key molecule that is involved in colon cancer cell survival and the inhibition of JAK1 by INCB01424 results in caspase-dependent apoptosis in colorectal cancer cells. The use of selective JAK1 inhibitors could be an attractive therapy against colorectal cancer, but further clinical investigations are needed to test this possibility.

Optimizing electrical activation of porcine oocytes by adjusting pre- and post-activation mannitol exposure times.

Modifying electrical activation conditions have been used to improve in vitro embryo production and development in pigs. However, there is insufficient information about correlations of porcine embryo development with oocyte pre- and post-activation conditions. The purpose of this study was to compare the developmental rates of porcine oocytes subjected to different mannitol exposure times, either pre- or post-electrical activation, and to elucidate the reason for the optimal mannitol exposure time. Mannitol exposure times around activation were adjusted as 0, 1, 2 or 3 min. Blastocyst development were checked on day 7. Exposure of oocytes to mannitol for 1 or 2 min before electrical activation produced significantly higher blastocyst rates than exposure for 0 or 3 min. There was no significant difference in blastocyst rates when activated oocytes were exposed to mannitol for 0, 1, 2 or 3 min after electrical activation. While exposure of oocytes to mannitol for 1 min pre- and 3 min post-activation showed significantly higher blastocyst development than 0 min pre- and 0 min post-activation. It also showed higher maintenance of normal oocyte morphology than exposure for 0 min pre- and 0 min post-activation. In conclusion, exposure of oocytes to mannitol for 1 min pre- and 3 min post-activation seems to be optimal for producing higher in vitro blastocyst development of porcine parthenogenetic embryos. The higher blastocyst development is correlated with higher maintenance of normal morphology in oocytes exposed to mannitol for 1 min pre- and 3 min post-activation.

Technical tips and issues of biliary stenting, focusing on malignant hilar obstruction.

In patients with inoperable hilar cholangiocarcinoma (HCCA), palliative endoscopic or percutaneous drainage provides benefits in terms of symptomatic improvement and quality of life. Endoscopic biliary stent placement is considered the gold standard, with metal stents preferred over plastic stents in patients with more than three months of life expectancy. However, the endoscopic management of advanced hilar obstruction is often more challenging and complex than distal malignant biliary obstructions. Recently, the Asia-Pacific working group on hepatobiliary cancers produced consensus recommendations on the use of endoscopic vs. percutaneous drainage and unilateral vs. bilateral drainage in the management of HCCA. However, these guidelines must be weighed against context-specific information, such as the volume of liver drainage required, life expectancy of the patient, and the available expertise. In this literature review, we describe the issues commonly encountered during endoscopic biliary stenting for malignant hilar obstruction and provide technical guidance to improve success rates and patient outcomes.

Influence of enzyme and transporter polymorphisms on trough imatinib concentration and clinical response in chronic myeloid leukemia patients.

BACKGROUND: This study explored the impact of genetic polymorphisms in cytochrome P450 (CYP) enzymes and transporters on the plasma trough concentration of imatinib mesylate (IM) and clinical response in chronic myeloid leukemia (CML). PATIENTS AND METHODS: In total, 82 patients with CML who had been administered 400 mg IM daily for over 6 months were genotyped for 11 single-nucleotide polymorphisms in nine genes (CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, ABCB1, SLC22A1, SLC22A2 and ABCG2) using blood samples. The trough imatinib concentration and clinical responses were assessed 6 months after the initiation of IM therapy. RESULTS: The CC, CA and AA genotypes in ABCG2 421C>A gave significantly different frequencies for the major molecular response (MMR) (P = 0.02). However, no significant differences were found between the genotypes of the CYP enzymes and transporters identified in this study and the imatinib plasma trough concentrations and clinical response frequencies, except for the correlation of ABCG2 with MMR. CONCLUSIONS: The results of the present study may indicate that the ABCG 421C>A genetic polymorphism influences the MMR of imatinib in patients with CML.

Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures.

BACKGROUND AND STUDY AIMS: Endoscopic bilateral drainage for inoperable malignant hilar biliary strictures (HBS) using metal stents is considered to be technically difficult. Furthermore, endoscopic revision of bilateral stenting after occlusion can be challenging. This study was performed to evaluate the long-term efficacy of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents in high-grade malignant HBS and planned endoscopic bilateral revision. PATIENTS AND METHODS: A total of 84 patients with inoperable high-grade malignant HBS were enrolled from three academic tertiary referral centers. Two cross-wired metal stents were inserted using a bilateral stent-in-stent placement method. Bilateral endoscopic revision was also performed during follow-up using either identical metal stents or plastic stents. The main outcome measurements were technical and functional success, complications, stent patency, and endoscopic revision efficacy. RESULTS: The technical and clinical success rates of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents were 95.2% (80/84) and 92.9% (78/84), respectively. Median patency (range) and survival were 238 days (10-429) and 256 days (10-1130), respectively. Obstruction of primary bilateral stents occurred in 30.8% (24/78) of patients with functionally successful stent placement. The technical and clinical success rates of planned bilateral endoscopic revision for occluded stents were 83.3% (20/24) and 79.2% (19/24), respectively. For revision, bilateral metallic stents were placed in 11 patients (55.0%); the remaining patients received plastic stents. CONCLUSIONS: Palliative endoscopic bilateral stent-in-stent placement of cross-wired metallic stents was effective in patients with inoperable HBS. Revision endoscopic bilateral stenting may be feasible and successful in cases where the primary deployed metal stents are occluded.

Epigenetic regulation of myofibroblast differentiation and extracellular matrix production in nasal polyp-derived fibroblasts.

BACKGROUND: Nasal polyposis is a multi-factorial disease associated with chronic inflammatory condition of the paranasal sinuses. Myofibroblast differentiation and extracellular matrix (ECM) accumulation are involved in the pathogenesis of nasal polyposis. OBJECTIVE: The aim of this study was to study the effect of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, on transforming growth factor (TGF)-ß1-induced myofibroblast differentiation and ECM accumulation in nasal polyp-derived fibroblasts (NPDFs). METHODS: Nasal polyp-derived fibroblasts were isolated from nasal polyps of patients who have chronic rhinosinusitis with nasal polyp. TSA was treated in TGF-ß1-induced NPDFs. Expression levels of HDAC2, α-smooth muscle actin (SMA), TGF-ß1, collagen type I, acetylated Histone H3, acetylated Histone H4, phosphorylated Smad2/3 and Smad7 were determined by RT-PCR, western blot and/or immunofluorescent staining. The total collagen amount production was analysed by Sircol soluble collagen assay and contractile activity was measured by collagen gel contraction assay. HDAC2 inhibition by TSA or HDAC2 silencing was established by RT-PCR and western blot. The epigenetic effect on α-SMA gene inactivation was examined by chromatin immunoprecipitation assay. Proliferation was determined by Ki67-positive cell staining and cytotoxicity was assessed by 3-(4,5- dimethylthiazol-2yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. RESULTS: The expression levels of HDAC2, α-SMA and TGF-ß1 were increased in nasal polyp tissues compared to normal inferior turbinate tissues. TSA and HDAC2 silencing inhibited expression levels α-SMA, collagen and HDAC2. TSA induced hyperacetylation of histone and suppressed opening of α-SMA gene promoter in TGF-ß1-induced NPDFs. TSA inhibited TGF-ß1-induced Smad 2/3 and rescued TGF-ß1-suppressed Smad7 signalling pathway. Finally, TSA blocked proliferation in TGF-ß1-induced NPDFs and has no cytotoxic effect in NPDFs. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that HDAC inhibition is associated with myofibroblast differentiation and extracelluar matrix accumulation in nasal polyposis. TSA may be useful as an inhibitor of nasal polyp growth, and thus has potential to be used as a novel treatment option for nasal polyposis.

Direct peroral cholangioscopy using an ultraslim upper endoscope for management of residual stones after mechanical lithotripsy for retained common bile duct stones.

BACKGROUND AND STUDY AIMS: The incidence of residual stones after mechanical lithotripsy for retained common bile duct (CBD) stones is relatively high. Peroral cholangioscopy using a mother-baby system may be useful for confirming complete extraction of stones, but has several limitations regarding routine use. We evaluated the role of direct peroral cholangioscopy (DPOC) using an ultraslim upper endoscope for the evaluation and removal of residual CBD stones after mechanical lithotripsy. PATIENTS AND METHODS: From August 2006 to November 2010, 48 patients who had undergone mechanical lithotripsy for retained CBD stones with no evidence of filling defects in balloon cholangiography were recruited. The bile duct was inspected by DPOC after balloon cholangiography. Detected residual CBD stones were directly retrieved with a basket or balloon catheter under DPOC. The incidence of residual stones detected by DPOC, and the success rate of residual stone retrieval under DPOC were investigated. RESULTS: DPOC was successfully performed in 46 of the 48 patients (95.8%). Of these, 13 patients (28.3%) had residual CBD stones (mean number 1.4, range 1-3; mean diameter 4.5 mm, range 2.3-9.6). The residual stones were removed directly under DPOC in 11 of these patients (84.6%). There were no complications associated with DPOC or stone removal. CONCLUSION: DPOC using an ultraslim upper endoscope is a useful endoscopic procedure for the evaluation and extraction of residual stones after mechanical lithotripsy for retained CBD stones.

Esophageal submucosal dissection under steady pressure automatically controlled endoscopy (SPACE): a randomized preclinical trial.

BACKGROUND AND STUDY AIMS: A new overtube system has been developed for steady pressure automatically controlled endoscopy (SPACE) in the gastrointestinal tract. The objectives of this study were to validate the feasibility and safety of SPACE in the esophagus, and to evaluate its potential advantages over conventional (manually insufflating) endoscopy in endoscopic submucosal dissection (ESD). METHODS: This was a multicenter preclinical trial using acute porcine models (n = 20). In Experiment 1 (feasibility/safety study), SPACE was attempted in the esophagus with continuous monitoring of cardiopulmonary parameters and intraluminal pressures in the downstream bowel. Different insufflation pressures were tested to optimize the insufflation condition. Each session was video-recorded and scored by blinded reviewers. In Experiment 2 (randomized trial), esophageal ESD was attempted using either SPACE or conventional endoscopy, and results were compared. RESULTS: In Experiment 1, SPACE was performed safely without intraluminal pressure elevation in the downstream bowel. According to video review, SPACE provided more stable, reproducible, and rapid visualization than conventional endoscopy. The insufflation pressure was optimized at 14 mmHg for esophageal SPACE. In Experiment 2, ESD was completed in all animals. The ESD time was significantly shorter with SPACE compared with conventional endoscopy (1326 vs. 1616 seconds; P = 0.009). Responses to questionnaires showed that 94 % - 100 % of participants considered SPACE to provide improved exposure and more uniform tissue tension than conventional endoscopy. Other data were comparable. CONCLUSIONS: SPACE is feasible, safe, and potentially effective for complicated endoscopic procedures, such as ESD. SPACE improves and standardizes endoscopic exposure and tissue tension. A clinical study is required to further confirm its safety and clinical effectiveness.

Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients.

BACKGROUND: To analyze the clinical features, outcomes including efficacy of treatment, and prognostic factors of patients with immunoglobulin D multiple myeloma (IgD MM). DESIGN AND METHODS: Seventy-five patients diagnosed with IgD MM were selected from the Korean Myeloma Registry database (www.myeloma.or.kr). RESULTS: Median age was 57 years and the main presenting features were bone pain (77%). Renal function impairment and hypercalcemia were present in 40 (53%) and 20 (27%) patients. Sixty-seven patients (89%) had lambda light chains. Forty-eight patients (64%) were of stage III by International Staging System. Twenty-six patients (53%) had chromosomal abnormalities mostly by conventional cytogenetics. Thirty-nine patients (54%) were treated with vincristine, adriamycin, and dexamethasone chemotherapy; the overall response rate (ORR) of 56%. Sixteen patients (22%) received first-line chemotherapy including new drugs (bortezomib or thalidomide), with an ORR of 81%. At a median follow-up time of 28.6 months, median overall survival (OS) was 18.5 months. Age, extramedullary plasmacytoma, del(13) or hypoploidy, serum ß(2) microglobulin level, and platelet count were significant prognostic factors for OS. CONCLUSIONS: IgD MM is an aggressive disease that is usually detected at an advanced stage. Despite a positive initial response, survival after relapse was dismal. Intensive treatment strategies before and following stem cell transplantation may improve outcomes in younger patients.

The analysis of PM2.5 and associated elements and their indoor/outdoor pollution status in an urban area.

UNLABELLED: In this study, elemental composition of PM2.5 and the status of indoor/outdoor pollution were investigated in a commercial building near a roadside area in Daejeon, Korea. A total of 60 parallel PM2.5 samples were collected both on the roof (outdoor) and in an indoor office of a building near a highly congested road during the spring and fall of 2008. The concentrations of 23 elements were analysed from these PM2.5 samples using instrumental neutron activation analysis. PM2.5 levels in indoor environment (47.6 ± 16.5 µg/m(3)) were noticeably higher than the outdoor levels (37.7 ± 17.2 µg/m(3)) with the I/O concentration ratio of 1.37 ± 0.33 [correlation coefficient (r) = 0.89, P < 0.001]. Principal component analysis results coincidently showed the predominance of sources such as soil dust, traffic, oil/coal combustion and road dust for both indoor and outdoor microenvironments. An isolated source in the indoor environment was assigned to environmental tobacco smoke (ETS) with high factor loading of Ce, Cl, I, K, La and Zn. The overall results of our study indicate that the sources of indoor constituents were strongly dependent on outdoor processes except for the ones affected by independent sources such as ETS. PRACTICAL IMPLICATIONS: An improved understanding of the factors affecting the indoor PM2.5 concentration levels can lead to the development of an efficient management strategy to control health risks from exposure to indoor PM2.5 and related toxic components. A comparison of our comprehensive data sets indicated that most indoor PM2.5 and associated elemental species were strongly enriched by indoor source activities along with infiltration of ambient outdoor air for a naturally ventilated building.