Follow-up of colorectal cancer patients: quality of life and attitudes towards follow-up.

The aims of our study were to assess the effect of follow-up on the quality of life of colorectal cancer patients and to assess the attitudes of patients towards follow-up as a function of patient characteristics. Patients who had been treated with curative intent were selected from four types of hospitals. Eighty-two patients were interviewed using a structured questionnaire, whereas 130 patients received the questionnaire by mail. To assess the effect of follow-up on the quality of life, the interviewed patients were randomly allocated to three groups and interviewed at different times in relation to the follow-up visit. Analysis did not show an effect of the follow-up visit on quality of life. Patients reported a positive attitude towards follow-up: it reassured them, they judged the communication with the physician to be positive, and they experienced only slight nervous anticipation and few other disadvantages. Patients reported a strong preference for follow-up, and a large majority would prefer follow-up even if it would not lead to earlier detection of a recurrence. Apart from living situation, no patient characteristics were clearly associated with the attitude towards follow-up. Implications for clinical practice are discussed

Short-term emission line and continuum variations in Mrk110

We present results of a variability campaign of Mrk110 performed with the 9.2-m Hobby-Eberly Telescope (HET) at McDonald Observatory. The high S/N spectra cover most of the optical range. They were taken from 1999 November through 2000 May. The average interval between the observations was 7.3 days and the median interval was only 3.0 days. Mrk110 is a narrow-line Seyfert 1 galaxy. During our campaign the continuum flux was in a historically low stage. Considering the delays of the emission lines with respect to the continuum variations we could verify an ionization stratification of the BLR. We derived virial masses of the central black hole from the radial distances of the different emission lines and from their widths. The calculated central masses agree within 20%. Furthermore, we identified optical HeI singlet emission lines emitted in the broad-line region. The observed line fluxes agree with theoretical predictions. We show that a broad wing on the red side of the [OIII]5007 line is caused by the HeI singlet line at 5016A.Comment: 11 pages, 16 figures, A&A Latex. Accepted for publication in A&A Main Journa

A Decade of Experience With Alemtuzumab Therapy for Severe or Glucocorticoid-Resistant Kidney Transplant Rejection

Alemtuzumab is used as lymphocyte-depleting therapy for severe or glucocorticoid-resistant kidney transplant rejection. However, the long-term efficacy and toxicity of alemtuzumab therapy are unclear. Therefore, all cases of alemtuzumab anti-rejection therapy between 2012 and 2022 in our institution were investigated. Graft survival, graft function, lymphocyte depletion, serious infections, malignancies, and patient survival were analyzed and compared with a reference cohort of transplanted patients who did not require alemtuzumab anti-rejection therapy. A total of 225 patients treated with alemtuzumab were identified and compared with a reference cohort of 1,668 patients. Over 60% of grafts was salvaged with alemtuzumab therapy, but graft survival was significantly poorer compared to the reference cohort. The median time of profound T- and B lymphocyte depletion was 272 and 344 days, respectively. Serious infection rate after alemtuzumab therapy was 54.1/100 person-years. The risk of death (hazard ratio 1.75, 95%-CI 1.28–2.39) and infection-related death (hazard ratio 2.36, 95%-CI 1.35–4.11) were higher in the alemtuzumab-treated cohort. In conclusion, alemtuzumab is an effective treatment for severe kidney transplant rejection, but causes long-lasting lymphocyte depletion and is associated with frequent infections and worse patient survival outcomes.</p

Ultraviolet and optical properties of Narrow-Line Seyfert 1 galaxies

Narrow Line Seyfert 1 (NLS1) galaxies are remarkable for their extreme continuum and emission line properties which are not well understood. New results bearing on the spectroscopic characteristics of these objects are presented here, with the aim of establishing their typical ultraviolet and optical spectral behavior. We employ HST observations of 22 NLS1s, which represent a substantial improvement over previous work in terms of data quality and sample size. High signal-to-noise NLS1 composite spectra are constructed, allowing accurate measurements of the continuum shape and the strengths, ratios, and widths for lines, including weak features which are barely identifiable in other Active Galactic Nuclei (AGN) composites. We find that the NLS1 sources have redder UV-blue continua than those typically measured in other quasars and Seyferts. Objects with UV line absorption show redder spectra, suggesting that dust is important in modifying the continuum shapes. The data also permit a detailed investigation of the previously proposed link between NLS1s and z >~ 4 quasars. Direct comparison of their composite spectra, as well as a Principal Component Analysis, suggest that high-z QSOs do not show a strong preference toward NLS1 behavior.Comment: 23 pages (incl. 9 figures, 4 tables), to appear in The Publications of the Astronomical Society of the Pacifi

Multiwavelength Monitoring of the Narrow-Line Seyfert 1 Galaxy Akn 564. II. Ultraviolet Continuum and Emission-line Variability

We present results of an intensive two-month campaign of approximately daily spectrophotometric monitoring of the narrow-line Seyfert 1 galaxy Akn 564 with HST. The fractional variability amplitude of the continuum variations between 1365-3000 A is ~6%, about a factor 3 less than that found in typical Seyfert 1 galaxies over a similar period of time. However, large amplitude, short time-scale flaring behavior is evident, with trough-to-peak flux changes of about 18% in approximately 3 days. We present evidence for wavelength-dependent continuum time delays, with the variations at 3000 A lagging behind those at 1365 A by about 1 day. These delays may be interpreted as evidence for a stratified continuum reprocessing region, possibly an accretion-disk structure. The Lyman-alpha 1216 emission-line exhibits flux variations of about 1% amplitude.Comment: 27 pages, 14 figures. Accepted by Astrophysical Journa

Alloreactive T cells to assess acute rejection risk in kidney transplant recipients

Background.Memory T cells are important mediators of transplant rejection but are not routinely measured before or after kidney transplantation. The aims of this study were as follows: (1) validate whether pretransplant donor-reactive memory T cells are reliable predictors of acute rejection (AR) (2) determine whether donor-reactive memory T cells can distinguish AR from other causes of transplant dysfunction. Methods.Samples from 103 consecutive kidney transplant recipients (2018-2019) were obtained pretransplantation and at time of for-cause biopsy sampling within 6 mo of transplantation. The number of donor-reactive interferon gamma (IFN-gamma) and interleukin (IL)-21-producing memory T cells was analyzed by enzyme-linked immunosorbent spot (ELISPOT) assay. Results.Of the 63 patients who underwent a biopsy, 25 had a biopsy-proven acute rejection (BPAR; 22 aTCMR and 3 aAMR), 19 had a presumed rejection, and 19 had no rejection. Receiver operating characteristic analysis showed that the pretransplant IFN-gamma ELISPOT assay distinguished between patients who later developed BPAR and patients who remained rejection-free (area under the curve [AUC] 0.73; sensitivity 96% and specificity 41%). Both the IFN-gamma and IL-21 assays were able to discriminate BPAR from other causes of transplant dysfunction (AUC 0.81; sensitivity 87% and specificity 76% and AUC 0.81; sensitivity 93% and specificity 68%, respectively). Conclusions.This study validates that a high number of donor-reactive memory T cells before transplantation is associated with the development of AR after transplantation. Furthermore, it demonstrates that the IFN-gamma and IL-21 ELISPOT assays are able to discriminate between patients with AR and patients without AR at the time of biopsy sampling.Personalised Therapeutic

Ex Vivo Administration of Mesenchymal Stromal Cells in Kidney Grafts Against Ischemia-reperfusion Injury-Effective Delivery Without Kidney Function Improvement Posttransplant

Background. Mesenchymal stromal cell (MSC) therapy may improve renal function after ischemia-reperfusion injury in transplantation. Ex vivo renal intraarterial administration is a targeted delivery method, avoiding the lung vasculature, a known barrier for cellular therapies. In a randomized and blinded study, we tested the feasibility and effectiveness of MSC therapy in a donation after circulatory death autotransplantation model to improve posttransplant kidney function, using an ex vivo MSC delivery method similar to the clinical standard procedure of pretransplant cold graft flush. Methods. Kidneys exposed to 75 minutes of warm ischemia and 16 hours of static cold storage were intraarterially infused ex vivo with 10 million male porcine MSCs (Tx-MSC, n = 8) or vehicle (Tx-control, n = 8). Afterwards, the kidneys were autotransplanted after contralateral nephrectomy. Biopsies an hour after reperfusion confirmed the presence of MSCs in the renal cortex. Animals were observed for 14 days. Results. Postoperatively, peak plasma creatinine was 1230 and 1274 mu mol/L (Tx-controls versus Tx-MSC, P = 0.69). During follow-up, no significant differences over time were detected between groups regarding plasma creatinine, plasma neutrophil gelatinase-associated lipocalin, or urine neutrophil gelatinase-associated lipocalin/creatinine ratio. At day 14, measured glomerular filtration rates were 40 and 44 mL/min, P = 0.66. Renal collagen content and fibrosis-related mRNA expression were increased in both groups but without significant differences between the groups. Conclusions. We demonstrated intraarterial MSC infusion to transplant kidneys as a safe and effective method to deliver MSCs to the graft. However, we could not detect any positive effects of this cell treatment within 14 days of observation

Clinical Translation of Ex Vivo Sentinel Lymph Node Mapping for Colorectal Cancer Using Invisible Near-Infrared Fluorescence Light

BACKGROUND: Sentinel lymph node (SLN) mapping in colorectal cancer may have prognostic and therapeutic significance; however, currently available techniques are not optimal. We hypothesized that the combination of invisible near-infrared (NIR) fluorescent light and ex vivo injection could solve remaining problems of SLN mapping in colorectal cancer. METHODS: The FLARE imaging system was used for real-time identification of SLNs after injection of the NIR lymphatic tracer HSA800 in the colon and rectum of (n = 4) pigs. A total of 32 SLN mappings were performed in vivo and ex vivo after oncologic resection using an identical injection technique. Guided by these results, SLN mappings were performed in ex vivo tissue specimens of 24 consecutive colorectal cancer patients undergoing resection. RESULTS: Lymph flow could be followed in real-time from the injection site to the SLN using NIR fluorescence. In pigs, the SLN was identified in 32 of 32 (100%) of SLN mappings under both in vivo and ex vivo conditions. Clinically, SLNs were identified in all patients (n = 24) using the ex vivo strategy within 5 min after injection of fluorescent tracer. Also, 9 patients showed lymph node involvement (N1 disease). In 1 patient, a 3-mm mesenteric metastasis was found adjacent to a tumor-negative SLN. CONCLUSIONS: The current pilot study shows proof of principle that ex vivo NIR fluorescence-guided SLN mapping can provide high-sensitivity, rapid, and accurate identification of SLNs in colon and rectum. This creates an experimental platform to test optimized, non-FDA-approved NIR fluorescent lymphatic tracers in a clinical setting.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Raman Scattered He II Line in the Planetary Nebula M2-9 and the Symbiotic Stars RR Telescopii and He 2-106

In this Letter, we report the detection of an emission feature around 6545 \AA in the spectra of the bipolar planetary nebula M2-9 and the symbiotic stars RR Telescopii and He 2-106 and propose to identify it as the He II Raman scattered feature. This feature was predicted by Nussbaumer, Schmid & Vogel (1989), who suggested that it is formed through Raman scattering by atomic hydrogen of He II $n=6\to n=2$ photons with slightly shorter wavelength than that of Ly$\beta$. The scattering cross section $\sim 10^{-20}{\rm cm^2}$ for this process implies the existence of a neutral hydrogen component with a column density $N_{HI}\sim 10^{20}{\rm cm^{-2}}$ around the He II emission regions in these objects, which are believed to be associated with the mass loss process in the late stage of stellar evolution. Brief discussions on the astrophysical implications of Raman scattering in these objects are presented.Comment: 8 pages, 2 figures, accepted for publication in the Astrophysical Journal Letter

Melanoma-inhibiting activity (MIA) mRNA is not exclusively transcribed in melanoma cells: low levels of MIA mRNA are present in various cell types and in peripheral blood

The detection of minimal amounts of melanoma cells by tyrosinase reverse transcription polymerase chain reaction (RT-PCR) is seriously hampered by false negative reports in blood of melanoma patients with disseminated melanoma. Therefore, additional assays which make use of multiple melanoma markers are needed. It has been shown that introduction of multiple markers increases the sensitivity of detection. Melanoma inhibitory activity (MIA) is one such melanoma-specific candidate gene. To test the specificity of MIA PCR, we performed 30 and 60 cycles of PCR with two different sets of MIA specific primers on 19 melanoma and 16 non-melanoma cell lines. MIA mRNA was detected in 16 out of 19 melanoma cell lines and in seven out of 16 non-melanoma cell lines after 30 cycles of PCR. However, MIA mRNA could be detected in all cell lines after 60 cycles of PCR. Also, in 14 out of 14 blood samples of melanoma patients, five out of six blood samples of non-melanoma patients and in seven out of seven blood samples of healthy volunteers, MIA mRNA was detected after 60 cycles of PCR, whereas no MIA PCR product could be detected in any of the blood samples after 30 cycles of PCR. We conclude that low levels of MIA transcripts are present in various normal and neoplastic cell types. Therefore, MIA is not a suitable marker gene to facilitate the detection of minimal amounts of melanoma cells in blood or in target organs of the metastatic process. © 1999 Cancer Research Campaig