Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

The 100 Most-Cited Articles Focused on Ultrasound Imaging: A Bibliometric Analysis.

Purpose The number of citations that an article has received reflects its impact on a particular research area. The aim of this study was to identify the 100 most-cited articles focused on ultrasound (US) imaging and to analyze the characteristics of these articles. Methods We determined the 100 most-cited articles on US imaging via the Web of Science database, using the search term. The following parameters were used to analyze the characteristics of the 100 most-cited articles: publication year, journal, journal impact factor, number of citations and annual citations, authors, department, institution, country, type of article, and topic. Results The number of citations for the 100 most-cited articles ranged from 1849 to 341 (median: 442.0) and the number of annual citations ranged from 108.0 to 8.1 (median: 22.1). The majority of articles were published in 1990 - 1999 (39 %), published in radiology journals (20 %), originated in the United States (45 %), were clinical observation studies (67 %), and dealt with the vessels (35 %). The Department of Internal Medicine at the University of California and the Research Institute of Public Health at the University of Kuopio (n = 4 each) were the leading institutions and Salonen JT and Salonen R (n = 4 each) were the most prolific authors. Conclusion Our study presents a detailed list and analysis of the 100 most-cited US articles, which provides a unique insight into the historical development in this field.

Percutaneous radiofrequency ablation for symptomatic uterine leiomyomas: a systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) in the treatment of uterine leiomyomas. MATERIALS AND METHODS: Medline, Embase, and Cochrane databases were searched through August 2014 for all relevant studies on RFA for uterine leiomyomas. The efficacy and safety of RFA were assessed using the outcome measures of tumor volume, symptom severity score, health-related quality of life (HRQL) score, procedure-related complications, and reintervention. The authors calculated pooled event rates with 95% confidence intervals using random-effects model to assess the effects of RFA. RESULTS: Eight observational studies were identified as eligible for inclusion in this meta-analysis and included 370 patients. All analyzed outcomes showed statistically significant improvements from baseline to final follow-up. Twenty-seven complications were identified and five of them qualified as major complications. Five patients required reintervention after RFA. CONCLUSIONS: Percutaneous RFA is an effective and safe treatment for patients with uterine leiomyomas.

Inhibition of monocarboxylate transporter-4 depletes stem-like glioblastoma cells and inhibits HIF transcriptional response in a lactate-independent manner.

Hypoxic regions are frequent in glioblastoma (GBM), the most common type of malignant adult brain tumor, and increased levels of tumor hypoxia have been associated with worse clinical outcomes. To unmask genes important in hypoxia, we treated GBM neurospheres in hypoxia and identified monocarboxylate transporter-4 (MCT4) as one of the most upregulated genes. To investigate the clinical importance of MCT4 in GBM, we examined clinical outcomes and found that MCT4 overexpression is associated with shorter patient survival. Consistent with this, MCT4 upregulation correlated with the aggressive mesenchymal subset of GBM, and MCT4 downregulation correlated with the less aggressive G-CIMP (Glioma CpG Methylator Phenotype) subset of GBM. Immunohistochemical analysis of tissue microarrays confirmed that MCT4 protein levels were increased in high-grade as compared with lower-grade astrocytomas, further suggesting that MCT4 is a clinically relevant target. To test the requirement for MCT4 in vitro, we transduced neurospheres with lentiviruses encoding short-hairpin RNAs (shRNAs) against MCT4, resulting in growth inhibition of 50-80% under hypoxia in two lines. MCT4 knockdown was associated with a decreased percentage of cells expressing the stem-cell marker CD133 and increased apoptotic fraction. We also found that flow-sorted CD133-positive cells had almost sixfold higher MCT4 levels than CD133-negative cells, suggesting that the stem-like population might have a greater requirement for MCT4. Most importantly, MCT4 silencing also slowed GBM intracranial xenograft growth in vivo. Interestingly, whereas MCT4 is a well-characterized lactate exporter, we found that both intracellular and extracellular lactate levels did not change following MCT4 silencing, suggesting a novel lactate export-independent mechanism for growth inhibition in GBMs. To identify this potential mechanism, we performed microarray analysis on control and shMCT4-expressing neurospheres and found a dramatic reduction in the expression of multiple Hypoxia-Inducible Factor (HIF)-regulated genes following MCT4 knockdown. The overall reduction in HIF transcriptional response was further validated using a hypoxia response element (HRE)-dependent green-fluorescent protein (GFP) reporter line.

Colour Doppler sonography of hepatic haemangiomas with arterioportal shunts.

OBJECTIVES: To determine the frequency of intratumoural flow and peritumoural hepatofugal portal flow using colour Doppler sonography (CDS) on hepatic haemangiomas with arterioportal shunt (APS), and to investigate possible factors that may affect the capability of CDS to depict such findings. METHODS: The study included 45 patients (35 men, 10 women; mean age, 56 years) with hepatic haemangiomas with APS on CT or MRI. Locating the tumour on greyscale sonography, the depth, size and echogenicity of the tumour were evaluated. CT or MR images were evaluated for fatty liver. CDS was performed to determine the presence of intratumoural flow and peritumoural hepatofugal portal flow. Differences in frequency of intratumoural flow and peritumoural hepatofugal portal flow according to the depth, size, echogenicity and fatty liver were evaluated by Student's t-test and Fisher's exact test. RESULTS: On CDS, intratumoural flow and peritumoural hepatofugal portal flow were found in 66.7% and 60%, respectively. The tumour depth was the significant variable that affected the capability of CDS to depict such findings. The frequencies of intratumoural flow and peritumoural hepatofugal portal flow were as high as 88% and 80% for shallow (≤30 mm) lesions, and they were 40% and 35% for deep (>30 mm) lesions (p=0.0012; p=0.0051). CONCLUSION: CDS can commonly depict intratumoural flow and peritumoural hepatofugal portal flow in patients with hepatic haemangiomas with APS. Therefore, CDS should be routinely performed when an incidental mass is encountered during the screening sonography, especially when the lesion is shallow.

Characterization of the major allergens of Pachycondyla chinensis in ant sting anaphylaxis patients.

BACKGROUND: The ant species Pachycondyla chinensis, which has spread from Far Eastern Asia to New Zealand and North America, induces anaphylactic reactions in human with its sting. However, the major allergens of P. chinensis have not yet been characterized. METHODS: We selected seven patients with histories of anaphylaxis induced by P. chinensis. Two-dimensional electrophoresis (2-DE) was used to identify the major allergens. We subsequently performed Western blots for P. chinensis-specific IgEs, N-terminal amino acid sequencing, ESI-MS/MS, and RT-PCR using primers based on the N-terminal sequence. RESULTS: Six of the anaphylactic subjects had an IgE specific to a 23 kDa allergen of P. chinensis. Two candidates for major allergens, 23 kDa (pI 8.7) and 25 kDa (pI 6.2), were revealed by 2-DE using P. chinensis-specific IgE immunoblotting. In N-terminal sequencing and ESI-MS/MS analysis, 23 kDa (pI 8.7) and 25 kDa (pI 6.2) allergens, belonging to the protein families of antigen 5, were identified and share marked amino acid sequence similarity. The 23 kDa allergen is 206 amino acids in length and homology searches showed 54.0% and 50.0% homology with Sol i 3 and Ves v 5, respectively. CONCLUSION: The major allergens of P. chinensis are 23 kDa (pI 8.7) and 25 kDa (pI 6.2) proteins that belong to the antigen 5 family of proteins.

Detection and characterization of intracranial aneurysms with 16-channel multidetector row CT angiography: a prospective comparison of volume-rendered images and digital subtraction angiography.

BACKGROUND AND PURPOSE: The aim of our study was to compare multidetector row CT angiography (MDCTA) with digital subtraction angiography (DSA) in the detection and characterization of intracranial aneurysms. MATERIALS AND METHODS: In our blinded prospective study, 85 patients with suspected intracranial aneurysm (47 women, 38 men; age range, 19-83 years) underwent both 16-channel MDCTA and DSA. The MDCT angiograms were interpreted for the presence, location, size, ratio of the neck to the dome (N/D ratio), and lobularity of the aneurysms and relationship of the aneurysm with the adjacent arterial branches, by using volume-rendering techniques. MDCTA and DSA images (reference standard) were interpreted by 2 independent readers, and the results were compared. RESULTS: A total of 93 aneurysms were detected at DSA in 71 patients, whereas no aneurysms were detected in 14 patients. Compared with DSA, the overall sensitivity, specificity, and accuracy of MDCTA on a per-aneurysm basis were 92.5%, 93.3%, and 92.6%, respectively, for both independent readers. For aneurysms of <3 mm, however, MDCTA had a sensitivity of 74.1% for reader 1 and 77.8% for reader 2. There was excellent agreement between readers in the detection of aneurysms (kappa = 0.822). In addition, MDCTA was also accurate in determining N/D ratio of aneurysms, aneurysm lobularity, and adjacent arterial branches. CONCLUSION: MDCTA is accurate in the detection and characterization of intracranial aneurysms and can be used as a reliable alternative imaging technique to DSA in selected cases.

Effects of calibration on L-THIA GIS runoff and pollutant estimation.

Urbanization can result in alteration of a watershed's hydrologic response and water quality. To simulate hydrologic and water quality impacts of land use changes, the Long-Term Hydrologic Impact Assessment (L-THIA) system has been used. The L-THIA system estimates pollutant loading based on direct runoff quantity and land use based pollutant coefficients. The accurate estimation of direct runoff is important in assessing water quality impacts of land use changes. An automated program was developed to calibrate the L-THIA model using the millions of curve number (CN) combinations associated with land uses and hydrologic soil groups. L-THIA calibration for the Little Eagle Creek (LEC) watershed near Indianapolis, Indiana was performed using land use data for 1991 and daily rainfall data for six months of 1991 (January 1-June 30) to minimize errors associated with use of different temporal land use data and rainfall data. For the calibration period, the Nash-Sutcliffe coefficient was 0.60 for estimated and observed direct runoff. The calibrated CN values were used for validation of the model for the same year (July 1-December 31), and the Nash-Sutcliffe coefficient was 0.60 for estimated and observed direct runoff. The Nash-Sutcliffe coefficient was 0.52 for January 1, 1991 to December 31, 1991 using uncalibrated CN values. As shown in this study, the use of better input parameters for the L-THIA model can improve accuracy. The effects on direct runoff and pollutant estimation of the calibrated CN values in the L-THIA model were investigated for the LEC. Following calibration, the estimated average annual direct runoff for the LEC watershed increased by 34%, total nitrogen by 24%, total phosphorus by 22%, and total lead by 43%. This study demonstrates that the L-THIA model should be calibrated and validated prior to application in a particular watershed to more accurately assess the effects of land use changes on hydrology and water quality.

Forecasting land use change and its environmental impact at a watershed scale.

Urban expansion is a major driving force altering local and regional hydrology and increasing non-point source (NPS) pollution. To explore these environmental consequences of urbanization, land use change was forecast, and long-term runoff and NPS pollution were assessed in the Muskegon River watershed, located on the eastern coast of Lake Michigan. A land use change model, LTM, and a web-based environmental impact model, L-THIA, were used in this study. The outcomes indicated the watershed would likely be subjected to impacts from urbanization on runoff and some types of NPS pollution. Urbanization will slightly or considerably increase runoff volume, depending on the development rate, slightly increase nutrient losses in runoff, but significantly increase losses of oil and grease and certain heavy metals in runoff. The spatial variation of urbanization and its impact were also evaluated at the subwatershed scale and showed subwatersheds along the coast of the lake and close to cities would have runoff and nitrogen impact. The results of this study have significant implications for urban planning and decision making in an effort to protect and remediate water and habitat quality of Muskegon Lake, which is one of Lake Michigan's Areas of Concern (AOC), and the techniques described here can be used in other areas.

Molecular factors in human implantation: adhesion molecules, proteases and cytokines.

Successful human reproduction remains an enigma, but this is slowly changing in the current era of expanding scientific knowledge. The discovery of various molecular factors such as adhesion molecules, proteases and cytokines have in recent years been at the forefront of medical research. The growing importance of immunology in particular has led to novel new immuno-modulatory therapies and increasing research into this new aspect of reproductive immunology may well prove to be the most important breakthrough in understanding the fundamentals of human reproduction. Implantation represents the first step in the complex interactions and processes involved in foetal-maternal interaction, which continues throughout pregnancy gestation and culminates in the birth of an infant. It is therefore vital that we understand the myriad processes controlling implantation in order to build a firm foundation for exploring reproductive immunology research in the new millennium. This review brings together and presents an overview of the potential roles of currently known molecular factors such as adhesion molecules, proteases, cytokines and its interaction with the maternal immune response, incorporating the findings of previous published research performed by the author on cytokines and reproductive immunology.

Is propess a better method of induction of labour in nulliparous women.

Slow release prostaglandin pessary (propess) is compared with instant release prostaglandin gel (prostin) for the induction of labour in nulliparous women with a modified Bishop's score of less than 6. In this randomised study 50 women received prostin gel and 45 received propess. More than one dose of prostaglandin was required to achieve amniotomy more often in the propess group (53%) compared with the prostin group (34%) (P=0.03). Propess was unable to demonstrate any advantage over Prostin gel group. Propess was not cost-effective in this study.

Naturally acquired antibody responses to the C-terminal region of merozoite surface protein 1 of Plasmodium vivax in Korea.

We expressed a protein in Saccharomyces cerevisiae in order to evaluate the humoral immune responses to the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax. This protein (Pv200(18)) had a molecular mass of 18 kDa and was reactive with the sera of individuals with patent vivax malaria on immunoblotting analysis. The levels of immunoglobulin M (IgM) and IgG antibodies against Pv200(18) were measured in 421 patients with vivax malaria (patient group), 528 healthy individuals from areas of nonendemicity (control group 1), and 470 healthy individuals from areas of endemicity (control group 2), using the indirect enzyme-linked immunosorbent assay (ELISA) method. To study the longevity of the antibodies, 20 subjects from the patient group were also tested for the antibody levels once a month for 1 year. When the cutoff values for seropositivity were determined as the mean + 3 x standard deviation of the antibody levels in control group 1, both IgG and IgM antibody levels were negative in 98.5% (465 of 472) of control group 2. The IgG and IgM antibodies were positive in 88.1% (371 of 421) and 94.5% (398 of 421) of the patient group, respectively. The IgM antibody became negative 2 to 4 months after the onset of symptoms, whereas the IgG antibody usually remained positive for more than 5 months. In conclusion, indirect ELISA using Pv200(18) expressed in S. cerevisiae may be a useful diagnostic method for vivax malaria.

The role of T-helper cytokines in human reproduction.

OBJECTIVE: To explore the role of maternal periimplantation endometrial T-helper-1 (TH-1) and T-helper-2 (TH-2) cytokines in the success or failure of human reproduction and their relation to the endocrine system and subsequent pregnancy outcome. DESIGN: Controlled, prospective study. SETTING: A tertiary care hospital with a university-based reproductive medicine clinic. PATIENT(S): Healthy women and women with recurrent miscarriage who had no history of infertility or autoimmune disease. INTERVENTION(S): Measurement of qualitative cytokine expression by RT-PCR and quantitative by ELISA, also hormone levels and pregnancy outcome. MAIN OUTCOME MEASURE(S): Expression of TH-1 and TH-2 cytokines and correlation with hormone levels and subsequent pregnancy outcome. RESULT(S): Levels of TH-1 cytokines were significantly greater and higher in women with recurrent miscarriage compared with controls, whereas levels of TH-2 cytokine interleukin-6 were significantly lower in women with recurrent miscarriage than in controls. There was no correlation between cytokine expression and serum hormone levels, and periimplantation cytokine levels were not predictive of subsequent pregnancy outcome in women with recurrent miscarriage. CONCLUSION(S): This study demonstrated in vivo that women with recurrent miscarriage exhibit primarily TH-1 cytokines, whereas healthy women exhibit decreased TH-1 cytokines and increased TH-2 cytokines. This suggests a potential role for a dichotomous T-helper response in the mediation of subsequent reproductive events. This maternal T-helper response appears to operate independently of hormonal factors in influencing the success or failure of human reproduction, as no correlation was evident between serum hormone levels and cytokine levels. An attempt to use periimplantation TH-1 and TH-2 cytokine profiles as a predictor of subsequent pregnancy outcome (live birth or no live birth) was limited by the small number of patients studied.

Profile of cytokine mRNA expression in peri-implantation human endometrium.

The human embryo and subsequent fetus is a semi-allograft and immunologically foreign to the mother. Successful embryonic implantation and maintenance of normal pregnancy depends on intricate interactions between the invading embryo, maternal endometrium and maternal immune response. Cytokines are pivotal in determining the type of maternal T-helper immune response, which can be divided into T-helper 1 (TH1)-mediated delayed hypersensitivity and T-helper 2 (TH2)-mediated humoral immunity. We examined the pattern of TH1 [interleukin (IL)-2, IL-12 and interferon-gamma] and TH2 (IL-4 and IL-6) cytokine expression in the peri-implantation endometrium of 10 fertile, multiparous women. Endometrial samples were timed to the mid-cycle luteinizing hormone (LH) surge, with collection on days LH+7 to LH+9. Analysis for cytokine mRNA was by mRNA extraction and reverse transcription-polymerase chain reaction. The results show a lack of TH1 and predominant TH2 cytokine expression. We postulate that endometrial cytokines may contribute to the local modulation of maternal adaptive immune response in peri-implantation endometrium, to facilitate successful embryonic implantation and maintenance of pregnancy.

Cytokines and immuno-endocrine factors in recurrent miscarriage.

Recurrent miscarriage remains an enigma. The main aetiologies are endocrinological, immunological and unexplained. With the growth in molecular biology, it is now possible to look at the effect of these aetiologies in more detail, allowing greater understanding of the underlying pathogenesis.

Treatment of corneal neovascularization with argon laser.

Corneal neovascularization, which is associated with complications in corneal diseases, can cause lipid deposit, decreasing vision, and graft rejection after penetrating keratoplasty (PKP). Corneal laser photocoagulation using an argon laser or yellow dye laser for ablation of corneal neovascularization has been described. We performed corneal argon laser photocoagulation (CALP) in two male patients with corneal neovascularization after herpetic keratitis. One PKP was performed after CALP and restored good vision with no rejection of the graft during an 8 month follow-up period. In the other case we observed visual improvement and no recurrence of corneal neovascularization after CALP.

Surgical correction of hyperopia: a new experimental approach using X-incision and suture technique in rabbits.

BACKGROUND: A new experimental surgical technique to correct hyperopia by steepening the central corneal curvature was performed on the eyes of rabbits. METHODS: After X-shaped incisions at four quadrants of the paracentral cornea, four deep, transverse interrupted sutures were placed across the incisions and the knots were tightened to compress the corneal tissue in the direction of the suture. Twenty-three eyes of 12 albino rabbits were divided into group A (7 eyes) with a 4-millimeter diameter clear zone, group B (9 eyes) with a 6-millimeter diameter clear zone, and control group C, consisting of 7 contralateral eyes of group A without any incision or suture. RESULTS: There was significant (p < .01) steepening of the central cornea as measured by the keratometer at postoperative 8 weeks in group A (+1.88 diopters) and group B (+1.68 D) compared with that of the control group C (-3.44 D). The difference in effect of hyperopic correction between groups of A and B was not statistically significant. CONCLUSIONS: This procedure serves only as an experimental model of corneal response to incisions and sutures and is not for use in human corneas.

Ocular dimensions with aging in normal eyes.

To quantify the dynamic changes taking place in the anterior segment, we measured the anterior chamber depth (ACD), lens thickness (LT) and their difference between sexes and age groups in normal eyes using contact ultrasonography and anterior chamber photography. There were 141 women (241 eyes) and 76 men (130 eyes) between the ages of 10 and 70 years. In normal eyes, the lens thickness was increased and the anterior chamber depth was decreased with aging in both sexes. The anterior chamber depth showed an accelerated decrease between the 4th and 5th decades in females and the ratio of anterior chamber depth to axial length was smaller in females than in males after the 5th decade. The results suggested that the prevalence of angle closure glaucoma will be increased in females after middle age.

Measurement of the tear meniscus height using 0.25% fluorescein sodium.

Measuring the tear meniscus height (TMH) is easy after fluorescein installation, but the TMH after fluorescein instillation is higher than the TMH before fluorescein instillation. Therefore, we measured the time that the TMH after fluorescein instillation became the same with the TMH, we studied the difference in the TMH between normal eyes and dry eyes. The TMH 0.19 +/- 0.05 mm in the normal eyes and 0.10 +/- 0.04 mm in the dry eyes, and there was a significant difference between the 2 groups. The time that the TMH after fluorescein instillation became the same with the TMH before fluorescein instillation was 2.19 +/- 0.81 min. in the normal eyes and 2.29 +/- 0.73 min. in the dry eyes. Within 4 min. after fluorescein instillation, the TMH became the same with the TMH before fluorescein instillation in all cases and the height persisted until 7 min. after fluorescein instillation. Therefore, measuring the TMH will be easy if it is measured at 4-7 min. after fluorescein instillation.

An immunohistochemical and morphological study of amyloidosis complicating leprosy in Malaysian patients.

Congo red screening of tissue blocks from 37 consecutive autopsies on leprosy patients revealed 7 cases of systemic amyloidosis, indicating a prevalence rate of 19%. 5 were males and 2 females. All were ethnic Chinese. Their ages ranged from 52 to 85 years with a mean of 69 years. Six had lepromatous leprosy while the remaining 1 had tuberculoid leprosy. In all 7 cases, the amyloid was AA in type, being permanganate-sensitive and immunoreactive with anti-human AA protein antiserum. Hepatic deposition was limited to blood vessels, a pattern typical of AA (secondary) amyloidosis. With regard to renal involvement, 4 showed a predominantly vascular pattern of infiltration while 3 exhibited the more ominous glomerular pattern. Three died of chronic renal failure and 2 of congestive cardiac failure attributable to renal and cardiac amyloidosis respectively. One patient succumbed to septicaemia and the remaining 1 to acute myocardial infarction. AA amyloidosis remains a serious and significant complication of leprosy among Malaysians.