Challenges in overcoming advanced-stage or relapsed refractory extranodal NK/T-cell lymphoma: meta-analysis of individual patient data

IntroductionExtranodal NK/T-cell lymphoma (ENKTCL), a non-Hodgkin lymphoma, is known for its destructive local impact on nasal structures and systemic induction of inflammatory cytokines. Concurrent treatment with radiation and nonanthracycline- based chemotherapy has improved survival rates in patients with localized disease stages. However, survival outcomes vary significantly in advanced-stage and relapsed or refractory (R/R) cases.MethodsTherefore, we conducted a meta-analysis using random effects models to assess prognostic factors in advanced or R/R ENKTCL, employing a digital extractor on Kaplan–Meier graphs owing to the scarcity of published prospective trials for these patients.ResultsWe observed that patients with advanced ENKTCL treated with Lasparaginase had a median progression-free survival (PFS) of 14.3 months and an overall survival (OS) of 19 months. In R/R ENKTCL, PFS and OS were 11.7 and 15.6 months, respectively. Additionally, OS outcomes in advanced-stage ENKTCL were better in the asparaginase group than that in the non-asparaginase group, with PEG-asparaginase showing superior results compared with that using Lasparaginase. Epstein–Barr Virus (EBV)-DNA positivity in the bloodstream prior to treatment was associated with poor outcomes in advanced-stage ENKTCL, and similar trends were observed in patients with R/R ENKTCL and post-treatment EBV viremia.DiscussionCollectively, these findings suggest that chemotherapy with Lasparaginase or PEG-asparaginase can enhance survival in advanced or R/R ENKTCL. However, future strategies must be developed to effectively suppress EBV viremia and achieve a deep response toward tumor eradication

Crystallization Mechanism of a Family of Embedded Isoreticular Zeolites

We have recently been successful in predicting and synthesizing a series of body-centered cubic zeolites with expanding structural complexity and embedded isoreticular structures, termed the RHO family. Here we propose a plausible formation pathway for ECR-18, ZSM-25, and PST-20, the three members of this zeolite family, in the presence of tetraethylammonium ions as an organic structure-directing agent, based on the C-13 MAS NMR, IR, and CO2 adsorption results obtained from the solid products recovered as a function of time during their crystallization processes, together with the quantum-chemical calculation results. The nucleation of these three zeolites, all of which consist of seven different structural units, begins with the almost simultaneous construction of 26-hedral lta and 14-hedral t-plg cages and their subsequent connection via shared 8-rings in the diagonal direction of the cubic unit cell. As a logical next step, 8-hedral t-oto and 12-hedral t-phi cages are built around the preorganized t-plg cages. The remaining embedded spaces are readily filled up with 10-hedral t-gsm cages, as well as with t-oto and t-phi cages. Finally, 10-hedral d8r and 14-hedral pau cages are alternately constructed along the cubic edges. Over the outer surface of the resulting nuclei of the RHO family zeolites, the crystal growth may occur in a similar manner as described above.113sciescopu

Acute normovolemic hemodilution for a patient with secondary polycythemia undergoing aortic valve replacement due to severe aortic stenosis - A case report -

Background A high hematocrit level in patients with erythrocytosis is linked with increased blood viscosity and increased risk of thromboembolism. Therefore, it is necessary to adequately lower the hematocrit level before performing a high-risk surgery. Case A 67-year-old male was scheduled for aortic valve replacement due to severe aortic stenosis. The preoperative hematocrit level of this patient was very high due to secondary polycythemia by hypoxia. We decided to perform acute normovolemic hemodilution after anesthetic induction to reduce the risk of thromboembolism in the patient. The patient was discharged after a successful surgery and a post-operative period without any side effects. Conclusions We estimate that patients with secondary polycythemia may benefit from acute normovolemic hemodilution to reduce their hematocrit levels while undergoing cardiac surgery using cardiopulmonary bypass. However, it is necessary to control the hematocrit level, since a significant decrease can cause side effects

Anaemia and pathologic complete response rate according to carboplatin dose in HER2+ breast cancer treated with neoadjuvant TCHP

Abstract Grade 3/4 anaemia, which is mainly induced by carboplatin, frequently occurs in patients treated with neoadjuvant docetaxel/carboplatin/trastuzumab/pertuzumab (TCHP). However, dose reduction of carboplatin may raise concerns about the oncological outcome. This study investigated the pathologic complete response (pCR) rate, occurrence of grade 3/4 anaemia, and transfusion rate according to carboplatin dose in patients treated with neoadjuvant TCHP. We retrospectively analysed 294 patients treated with neoadjuvant TCHP between April 2015 and December 2020. Case matching was performed using propensity score matching. Among patients treated with neoadjuvant TCHP, carboplatin area under the plasma concentration–time curve 6 (AUC6) was used in 234 patients (79.6%) and upfront carboplatin AUC5 was used in 60 patients (20.4%). No significant difference in pCR rate was found between the two groups (AUC6: 70.9%, AUC5: 80.0%). In both oestrogen receptor‐positive (ER+) and ER‐ patients, no significant differences were observed between the AUC6 and AUC5 groups (ER+: 54.3% vs. 50.0%, ER‐: 81.7% vs. 86.0%). The case‐matched cohort showed consistent findings. The AUC5 group had lower frequencies of grade 3/4 anaemia (18.3% vs. 34.2%) and transfusion events (10.0% vs. 21.8%) than the AUC6 group. Compared with AUC5, carboplatin at AUC6 would associate with a 2.7‐fold increased risk of grade 3 or 4 chemotherapy‐induced anaemia. Carboplatin AUC5 has comparable cytotoxic effects to carboplatin AUC6 in patients with HER2+ breast cancer treated with six cycles of neoadjuvant TCHP, with fewer complications associated with clinically meaningful anaemia. AUC5 may be the optimal carboplatin dose to reduce TCHP‐induced anaemia in patients with HER2+ breast cancer treated with TCHP

Estrogen receptor alpha gene polymorphisms in patients with idiopathic premature ovarian failure

It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.This study was supported by a grant (01-PJ10-PG6-01GN13-0002) from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea.Yoon SH, 2008, HUM REPROD, V23, P688, DOI 10.1093/humrep/dem415Bretherick KL, 2008, FERTIL STERIL, V89, P318, DOI 10.1016/j.fertnstert.2007.03.008Altmae S, 2007, MOL HUM REPROD, V13, P521, DOI 10.1093/molehr/gam035Corbo RM, 2007, MOL HUM REPROD, V13, P537, DOI 10.1093/molehr/gam041Hsieh YY, 2007, MOL HUM REPROD, V13, P117, DOI 10.1093/molehr/gal099Kim SH, 2005, FERTIL STERIL, V84, P774, DOI 10.1016/j.fertnstert.2005.03.046Goswami D, 2005, HUM REPROD UPDATE, V11, P391Gennari L, 2005, AM J EPIDEMIOL, V161, P307, DOI 10.1093/aje/kwi055Barrett JC, 2005, BIOINFORMATICS, V21, P263, DOI 10.1093/bioinformatics/bth457MATTHEWS J, 2003, MOL INTERV, V3, P281Herrington DM, 2002, CIRCULATION, V105, P1879, DOI 10.1161/01.CIR.0000016173.98826.88Stavrou I, 2002, HUM REPROD, V17, P1101Weel AEAM, 1999, J CLIN ENDOCR METAB, V84, P3146Georgiou I, 1999, FERTIL STERIL, V72, P164Syrrou M, 1999, AM J MED GENET, V84, P306Anasti JN, 1998, FERTIL STERIL, V70, P1Conway GS, 1997, CURR OPIN OBSTET GYN, V9, P202Mosselman S, 1996, FEBS LETT, V392, P49SANO M, 1995, BIOCHEM BIOPH RES CO, V217, P378COULAM CB, 1986, OBSTET GYNECOL, V67, P604WALTER P, 1985, P NATL ACAD SCI USA, V82, P7889COULAM CB, 1983, FERTIL STERIL, V40, P693COULAM CB, 1982, FERTIL STERIL, V38, P645REBAR RW, 1982, J REPROD MED, V4, P179RICHARDS JS, 1976, ENDOCRINOLOGY, V99, P1562GOLDENBE.RL, 1972, ENDOCRINOLOGY, V91, P533

False positive and false negative FDG-PET scans in various thoracic diseases

Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is being used more and more to differentiate benign from malignant focal lesions and it has been shown to be more efficacious than conventional chest computed tomography (CT). However, FDG is not a cancer-specific agent, and false positive findings in benign diseases have been reported. Infectious diseases (mycobacterial, fungal, bacterial infection), sarcoidosis, radiation pneumonitis and post-operative surgical conditions have shown intense uptake on PET scan. On the other hand, tumors with low glycolytic activity such as adenomas, bronchioloalveolar carcinomas, carcinoid tumors, low grade lymphomas and small sized tumors have revealed false negative findings on PET scan. Furthermore, in diseases located near the physiologic uptake sites (heart, bladder, kidney, and liver), FDG-PET should be complemented with other imaging modalities to confirm results and to minimize false negative findings. Familiarity with these false positive and negative findings will help radiologists interpret PET scans more accurately and also will help to determine the significance of the findings. In this review, we illustrate false positive and negative findings of PET scan in a variety of diseases

FDG PET/CT Findings of Castleman Disease Assessed by Histologic Subtypes and Compared with Laboratory Findings

Castleman disease (CD) is a relatively rare lymphoproliferative disorder and the pathophysiology of the subtypes are incompletely understood. Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrates the metabolic activity of inflammatory and tumorous conditions. The FDG uptake intensity and sites of involved lesions on FDG PET/CT were assessed by histologic subtypes, and compared to the patient’s hemoglobin, platelet, albumin, and high-sensitivity C-reactive protein (hs-CRP) levels. In total, 60 PET/CT images of 44 consecutive CD patients were included: 4 (9%) unicentric and 40 (91%) multicentric; 21 (48%) hyaline vascular subtype, 16 (36%) plasma cell, and 7 (16%) mixed or unclassified. The maximum standardized uptake value (SUVmax) and tumor-to-liver (T/L) ratio of involved lymph nodes (LNs) were 5.3 ± 2.4 (range, 1.6–11.5) and 2.8 ± 1.6 (range, 1.1–9.6), respectively, with no significant difference between the histologic subtypes. Higher number of involved LN stations and presence of extra-nodal involvement on FDG PET/CT were associated with thrombocytopenia, hypoalbuminemia, and elevated hs-CRP levels (p values < 0.05). FDG-avidity was not different by histologic subtypes and did not correlate with laboratory findings. However, the extent of nodal and extra-nodal involvement as noted on FDG PET/CT was significantly associated with abnormal laboratory findings in patients with CD

Feasibility of Template-Guided Attenuation Correction in Cat Brain PET Imaging

Purpose: Attenuation correction (AC) is important in quantitative positron emission tomography (PET) imaging of medium-sized animals such as the cat. However, additional time for transmission (TX) scanning and tracer uptake is required in PET studies with animal-dedicated PET scanners because post-injection TX scanning is not available in these systems. The aim of this study was to validate a template-guided AC (TGAC) method that does not require TX PET data for AC in cat 2-deoxy-2-[F-(18)fluoro-D-glucose (FDG) brain PET imaging. Methods: PET scans were acquired using a microPET Focus 120 scanner. TX data were obtained using a (68)Ge point source before the injection of FDG. To generate the attention map (mu-map) template for the TGAC, a target image of emission (EM) PET was selected, and spatial normalization parameters of individual EM data onto the target were reapplied to the corresponding mu-maps. The inverse transformations of the mu-map template into the individual spaces were performed, and the transformed template was forward projected to generate the AC factor. The TGAC method was compared with measured AC (MAC) and calculated AC (CAC) methods using region of interest (ROI) and SPM analyses. Results: The ROI analysis showed that the activity of the TGAC EM PET images strongly correlated with those of the MAC data (y = 0.98x + 0.01, R(2)=0.96). In addition, no significant difference was observed in the SPM analysis. By contrast, the CAC showed a significantly higher uptake in the deep gray regions compared to the MAC (corrected P<0.05). The ROI correlation with MAC was worse than with the TGAC (R(2)=0.84). In SPM analysis for the voxel-wise group comparisons between before and after the induction of deafness, only the TGAC showed equivalent results with the MAC. Conclusions: The TGAC was reliable in cat FDG brain PET studies in terms of compatibility with the MAC method. The TGAC might be a useful option for increasing study throughput and decreasing the probability of subject movement. In addition, it might reduce the possible biological effects of long-term anesthesia on the cat brain in investigations using animal-dedicated PET scanners.This work was supported by grants from the World Class University Program (R32-10142), Atomic Energy R&D Program (2008-03852), Basic Atomic Energy Research Institute Program (M20508050002-05B0805-00210, 2008-02334), Nuclear R&D Program (M20702010002-08N0201-00200, 20090078289), and Brain Research Center of the 21st Century Frontier Research Program (M103KV010014-04K2201-01400) through the Korea Science and Engineering Foundation funded by the Ministry of Education, Science and Technology.Kim SJ, 2008, J NUCL MED, V49, P2057, DOI 10.2967/jnumed.108.053215Hofmann M, 2008, J NUCL MED, V49, P1875, DOI 10.2967/jnumed.107.049353Zhou VW, 2008, MOL IMAGING BIOL, V10, P315, DOI 10.1007/s11307-008-0157-0Vandervoort E, 2008, J NUCL MED, V49, P1852, DOI 10.2967/jnumed.108.051193Riemann B, 2008, Q J NUCL MED MOL IM, V52, P215Hong SJ, 2008, IEEE T NUCL SCI, V55, P882, DOI 10.1109/TNS.2008.924082Beyer T, 2008, EUR J NUCL MED MOL I, V35, P1142, DOI 10.1007/s00259-008-0734-0Kim JS, 2008, MOL IMAGING BIOL, V10, P154, DOI 10.1007/s11307-008-0140-9Judenhofer MS, 2008, NAT MED, V14, P459, DOI 10.1038/nm1700Catana C, 2008, P NATL ACAD SCI USA, V105, P3705, DOI 10.1073/pnas.0711622105van Velden FHP, 2008, PHYS MED BIOL, V53, P99, DOI 10.1088/0031-9155/53/1/007Woo SK, 2008, NUCL MED BIOL, V35, P143, DOI 10.1016/j.nucmedbio.2007.10.003KIM JS, 2008, NUCL MED MOL IMAGING, V42, P112Kim JS, 2007, J NUCL MED, V48, P1527, DOI 10.2967/jnumed.107.040550Judenhofer MS, 2007, RADIOLOGY, V244, P807, DOI 10.1148/radiol.2443061756Lee JS, 2007, PHARM RES, V24, P1202, DOI 10.1007/s11095-007-9264-xKIM JS, 2007, J NUCL MED S, V48, P411Zhang YM, 2006, MOL IMAGING BIOL, V8, P300, DOI 10.1007/s11307-006-0052-5Lehnert W, 2006, PHYS MED BIOL, V51, P4003, DOI 10.1088/0031-9155/51/16/008Herrero P, 2006, J NUCL MED, V47, P477KIM JS, 2006, NUCL MED MOL IMAGING, V40, P40Lee JS, 2005, EUR J NUCL MED MOL I, V32, P696, DOI 10.1007/s00259-004-1739-yChow PL, 2005, PHYS MED BIOL, V50, P1837, DOI 10.1088/0031-9155/50/8/014Montandon ML, 2005, NEUROIMAGE, V25, P278Pomper MG, 2005, CURR PHARM DESIGN, V11, P3247Waldherr C, 2005, J NUCL MED, V46, P114Ahn SH, 2004, HEARING RES, V196, P33, DOI 10.1016/j.heares.2004.05.012Green LA, 2004, J NUCL MED, V45, P1560Woody C, 2004, NUCL INSTRUM METH A, V527, P166, DOI 10.1016/j.nima.2004.03.114Toyama H, 2004, NUCL MED BIOL, V31, P251, DOI 10.1016/S0969-8051(03)00124-0Matsumura A, 2003, NEUROIMAGE, V20, P2040, DOI 10.1016/j.neuroimage.2003.08.020Knoess C, 2003, EUR J NUCL MED MOL I, V30, P737, DOI 10.1007/s00259-002-1052-6Yang HH, 2003, PROSTATE, V55, P39, DOI 10.1002/pros.10208Huber JS, 2002, PHYS MED BIOL, V47, P3535, DOI 10.1088/0031-9155/47/19/307Burger C, 2002, EUR J NUCL MED MOL I, V29, P922, DOI 10.1007/s00259-002-0796-3Weinzapfel BT, 2001, J NUCL MED, V42, P483Stodilka RZ, 2000, J NUCL MED, V41, P1569Watson CC, 2000, IEEE T NUCL SCI, V47, P1587, DOI 10.1109/23.873020Nuyts J, 1999, IEEE T NUCL SCI, V46, P1136, DOI 10.1109/23.790847Nuyts J, 1999, IEEE T MED IMAGING, V18, P393, DOI 10.1109/42.774167Ashburner J, 1999, HUM BRAIN MAPP, V7, P254Kinahan PE, 1998, MED PHYS, V25, P2046Kalter SS, 1997, LAB ANIM SCI, V47, P461Friston KJ, 1995, HUM BRAIN MAPP, V3, P165SMITH RJ, 1994, IEEE T NUCL SCI, V41, P1526, DOI 10.1109/23.322943SIEGEL S, 1992, IEEE T NUCL SCI, V39, P1117, DOI 10.1109/23.159770XU EZ, 1991, J NUCL MED, V32, P161CARSON RE, 1988, J NUCL MED, V29, P1558ROGERS JG, 1987, IEEE T MED IMAGING, V6, P239

A zeolite family with expanding structural complexity and embedded isoreticular structures

The prediction and synthesis of new crystal structures enable the targeted preparation of materials with desired properties. Among porous solids, this has been achieved for metal–organic frameworks1, 2, 3, but not for the more widely applicable zeolites4, 5, where new materials are usually discovered using exploratory synthesis. Although millions of hypothetical zeolite structures have been proposed6, 7, not enough is known about their synthesis mechanism to allow any given structure to be prepared. Here we present an approach that combines structure solution with structure prediction, and inspires the targeted synthesis of new super-complex zeolites. We used electron diffraction to identify a family of related structures and to discover the structural ‘coding’ within them. This allowed us to determine the complex, and previously unknown, structure of zeolite ZSM-25 (ref. 8), which has the largest unit-cell volume of all known zeolites (91,554 cubic ångströms) and demonstrates selective CO2 adsorption. By extending our method, we were able to predict other members of a family of increasingly complex, but structurally related, zeolites and to synthesize two more-complex zeolites in the family, PST-20 and PST-25, with much larger cell volumes (166,988 and 275,178 cubic ångströms, respectively) and similar selective adsorption properties. Members of this family have the same symmetry, but an expanding unit cell, and are related by hitherto unrecognized structural principles; we call these family members embedded isoreticular zeolite structures.</p