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1.
Int J Mol Sci ; 25(6)2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38542462

ABSTRACT

Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all UCs. Immune checkpoint inhibitors (ICIs) have been established for UCs. The prognostic and predictive potential of programmed cell death ligand 1 (PD-L1) expression to stratify patients benefiting from ICIs is not fully understood, and additional markers influencing the impact of PD-L1-mediated ICI response are needed. Previously, the chemokine-like MARVEL transmembrane domain-containing protein 6 (CMTM6) was identified as a positive regulator of PD-L1. Our aim was to investigate the expression profiles and impact of PD-L1 and CMTM6 protein status on the prognostic parameters and survival of UTUC patients. In this retrospective study, the combined positive score (CPS), tumor proportion score (TPS), and immune cell score (ICS) for PD-L1 and CMTM6 were determined. High PD-L1 CPS, ICS, and TPS were found in 77.4%, 58.3%, and 45.2% of cases, and high CMTM6 CPS, ICS, and TPS were seen in 52.5%, 51.5%, and 55.5% of cases, respectively. The scores of both markers had a significant positive correlation. High PD-L1 and CMTM6 expression was coupled with higher pT status, WHO grade, necrosis, and metastasis (p < 0.05, respectively). In the univariate survival analysis, patients with a PD-L1 ICS high and higher degree of intratumoral inflammation showed significantly longer overall survival. Compared to other studies on UC, our study shows a substantially higher rate of PD-L1-positive tumors. CMTM6 was associated with more aggressive tumors.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/metabolism , B7-H1 Antigen , Prognosis , Retrospective Studies , Ligands , Apoptosis , Biomarkers , Chemokines , MARVEL Domain-Containing Proteins/genetics
2.
Liver Int ; 43(1): 69-76, 2023 01.
Article in English | MEDLINE | ID: mdl-35861306

ABSTRACT

BACKGROUND AND AIMS: Achieving Hepatitis B e antigen seroconversion (HBeAg SC) at an earlier age confers a better prognosis. We examined baseline and post-partum factors associated with HBeAg SC after pregnancy. We developed a tool, the SydPregScore, to estimate the likelihood of HBeAg SC in the years after pregnancy. METHODS: A retrospective analysis of an HBeAg-positive pregnant cohort was conducted. Variables including baseline age, parity, alanine aminotransferase level, HBV viral load, quantitative HBsAg, use of antiviral therapy and post-partum flare were collected. Univariate and multivariate Cox regression analyses to determine predictors of HBeAg SC and develop a predictor score were performed. RESULTS: We analysed HBeAg SC rates in 220 pregnancies to 149 HBeAg-positive women from 2006 to 2019. At baseline, their median age was 33 (IQR 29-37), ALT 23 U/L (IQR 17-33) and viral load 8 log10 IU/mL (IQR 6.3-8.2 log10 IU/mL). The majority (133/198, 67.2%) received short-course antiviral therapy to prevent mother-to-child transmission, and 109/192 (56.8%) had a post-partum flare. HBeAg SC occurred in 74/220 (33.6%) after pregnancy (median follow-up 814 days, IQR 405-1531). Multivariate analysis identified baseline viral load <8 log10 IU/mL (HR 2.426 [1.224-4.809], p = .011), baseline ALT ≥2 ULN (HR 2.726 [1.299-5.721], p = .008) and age <35 (HR 2.859 [1.255-6.513], p = .012) to be positive predictors of HBeAg SC. The 'SydPreg Score' estimated the probability of HBeAg SC at 2000 days as 10%, 30%, 70% and 80% for 0, 1, 2, and 3 predictors respectively. CONCLUSION: The SydPreg Score allows the prediction of HBeAg SC in the years after pregnancy. Even in those without elevated ALT, age <35 and viral load <8 log10 IU/mL can identify women with a good chance of subsequent HBeAg SC. Those without a chance may benefit from viral suppression.


Subject(s)
Hepatitis B e Antigens , Hepatitis B, Chronic , Pregnancy , Humans , Female , Adult , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/drug therapy , Seroconversion , Retrospective Studies , Infectious Disease Transmission, Vertical/prevention & control , Hepatitis B Surface Antigens , DNA, Viral , Antiviral Agents/therapeutic use , Hepatitis B virus/genetics
3.
J Women Aging ; 34(3): 309-322, 2022.
Article in English | MEDLINE | ID: mdl-34097589

ABSTRACT

Coastal Carolina is a popular retirement destination. Ten individuals, previously interviewed regarding their decision to retire here, were re-interviewed after Hurricane Florence. This sample of eight women and two men, mean age 74.4 (range = 68-88), provided a unique opportunity to learn about their hurricane experiences and to compare their pre- and post-responses about their choice to move to the coast. Nine evacuated, including one to a local shelter. Respondents reported a lack of preparations, but neighbors played an important supportive role. Issues about the shelter and for single women were identified. Results have implications for future disaster preparations.


Subject(s)
Cyclonic Storms , Disaster Planning , Aged , Disaster Planning/methods , Female , Humans , Learning , Male , Retirement
4.
J Women Aging ; 32(1): 3-27, 2020.
Article in English | MEDLINE | ID: mdl-31663431

ABSTRACT

Data were collected at five elder cohousing neighborhoods to understand more about who lives in these communities, their reasons for moving, their satisfaction, and to explore the intersection between loneliness and sense of community. The average age of the predominantly white, female, and well-educated sample (n = 86, 56% response rate), was 68 ± 6.573 at move-in. Respondents moved in search of a sense of community and were generally satisfied with their experiences. Prevalence of loneliness was lower than the national average, but still affected 24% of the sample. Findings suggest that senior cohousing is delivering on the promise to promote sense of community.


Subject(s)
Housing for the Elderly/statistics & numerical data , Loneliness , Personal Satisfaction , Residence Characteristics , Aged , Aged, 80 and over , Female , Humans , Middle Aged
5.
Dig Dis Sci ; 64(5): 1158-1170, 2019 05.
Article in English | MEDLINE | ID: mdl-30569336

ABSTRACT

BACKGROUND: Short bowel syndrome results from extensive small bowel resection and induces adaptation of the remaining intestine. Ileocecal resection (ICR) is the most frequent situation in humans. Villus hypertrophy is one hallmark of mucosal adaptation, but the functional mechanisms of mucosal adaptation are incompletely understood. AIMS: The aim of the study was to characterize a clinically relevant model of short bowel syndrome but not intestinal failure in mice and to identify outcome predictors and mechanisms of adaptation. METHODS: Male C57BL6/J mice underwent 40% ICR and were followed for 7 or 14 days. Small bowel transection served as control. All mice underwent autopsy. Survival, body weight, wellness score, stool water content, plasma aldosterone concentrations, and paracellular permeability were recorded. RESULTS: Unlike controls, resected mice developed significant diarrhea with increased stool water. This was accompanied by sustained weight loss throughout follow-up. Villus length increased but did not correlate positively with adaptation. Plasma aldosterone concentrations correlated inversely with body weight at day 14. After ICR, intestinal epithelial (i.e., tight junctional) sodium permeability was increased. CONCLUSIONS: 40% ICR results in moderate to severe short bowel syndrome. Successful adaptation to the short bowel situation involves villus elongation but does not correlate with the degree of villus elongation alone. In addition, increased intestinal epithelial sodium permeability facilitates sodium-coupled solute transport. Hyperaldosteronism correlates with the severity of weight loss, indicates volume depletion, and counterregulates water loss.


Subject(s)
Disease Models, Animal , Hyperaldosteronism/metabolism , Intestinal Mucosa/metabolism , Short Bowel Syndrome/metabolism , Sodium/metabolism , Animals , Hyperaldosteronism/pathology , Intestinal Mucosa/pathology , Male , Mice , Mice, Inbred C57BL , Organ Culture Techniques , Random Allocation , Short Bowel Syndrome/pathology
6.
Acta Neurochir (Wien) ; 161(8): 1723-1732, 2019 08.
Article in English | MEDLINE | ID: mdl-31254065

ABSTRACT

BACKGROUND: The objective of this study was to evaluate the morphology of glioblastoma on structural pretreatment magnetic resonance imaging (MRI), defining imaging prognostic factors. METHOD: We conducted a retrospective analysis of MR images from 114 patients harboring a primary glioblastoma, derived from two neurosurgical departments. Tumor segmentation was carried out in a semi-automated fashion. Tumor compartments comprised contrast-enhancing volume (CEV+), perifocal hyperintensity on fluid-attenuated inversion recovery (FLAIR) images (FLAIR+) excluding CEV+, and a non-enhancing area within the CEV+ lesion (CEV-). Additionally, two ratios were calculated from these volumes, the edema-tumor ratio (ETR) and necrosis-tumor ratio (NTR). All patients received surgical resection, followed by concomitant radiation and chemotherapy. RESULTS: Tumor segmentation revealed the strongest correlation between the CEV+ volume and the CEV-, presenting intratumoral necrosis (p < 0.001). The relation between the tumor surrounding the FLAIR+ area and the CEV+ volume and the ETR is inversely correlated (p = 0.001). The most important prognostic factor in multivariable analysis was NTR (HR 2.63, p = 0.016). The cut-off value in our cohort for NTR was 0.33, equivalent to a decrease in survival if the necrotic core of the tumor (CEV-) accounts for more than 33% of the tumor mass itself (CEV+). CONCLUSIONS: Our data emphasizes the importance of the necrosis-tumor ratio as a biomarker in glioblastoma imaging, rather than single tumor compartment volumes. NTR can help to identify a subset of tumors with a higher resistance to therapy and a dismal prognosis.


Subject(s)
Brain Neoplasms/diagnostic imaging , Glioblastoma/diagnostic imaging , Adult , Aged , Brain Neoplasms/epidemiology , Brain Neoplasms/pathology , Female , Glioblastoma/epidemiology , Glioblastoma/pathology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Necrosis , Prognosis , Survival Analysis
7.
Liver Int ; 38(7): 1212-1219, 2018 07.
Article in English | MEDLINE | ID: mdl-29532580

ABSTRACT

BACKGROUND & AIMS: Antipartum antiviral therapy in the setting of high viral load is recommended to prevent mother-to-child transmission of hepatitis B although recommended viral load cut-offs vary. Quantitative HBsAg has been proposed as an alternative screening strategy to identify high viral load in this setting. Guidelines suggest testing all infants for vaccine response and infection. We set out to re-examine viral load cut-offs; the predictive value of quantitative HBsAg and the need for follow-up infant testing in our cohort. METHODS: A retrospective cohort study of 469 HBsAg positive mother-baby pairs from 2 tertiary hospitals in Sydney was performed. Antiviral therapy (lamivudine or tenofovir disoproxil fumarate) was offered to women with viral load ≥6 log10  IU/mL (high) from 32 weeks gestation. Transmission and vaccine response was analysed according to viral load. The utility of quantitative HBsAg in identifying high viral load was examined. RESULTS: Mother-to-child transmission only occurred in setting of high viral load, in 0.85% (1/117) of those who received antiviral therapy and in 8.66% (2/23) of those who chose not to. Quantitative HBsAg did not accurately identify high-risk mothers HBV DNA ≥6 log10  IU/mL. Successful infant vaccine response was 98.7% overall, and 99.4% when viral load was <6 log10  IU/mL. CONCLUSION: Antiviral therapy initiated at 32 weeks when maternal viral load is ≥6 log10  IU/mL almost completely abrogates transmission. Quantitative HBsAg does not reliably predict high viral load. When maternal viral load is <6 log10  IU/mL, high vaccine efficacy and zero transmission suggests testing infants is of little value.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B Vaccines/therapeutic use , Hepatitis B/drug therapy , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy Complications, Infectious/prevention & control , Viral Load , Adult , Australia , Female , Gestational Age , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/genetics , Humans , Infant , Infant, Newborn , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Infectious/virology , ROC Curve , Retrospective Studies
8.
BMC Pregnancy Childbirth ; 18(1): 118, 2018 May 02.
Article in English | MEDLINE | ID: mdl-29716537

ABSTRACT

BACKGROUND: The aim of the study was to investigate the accuracy of ultrasound-derived estimated fetal weight (EFW) and to determine its impact on management and outcome of delivery. METHODS: In this single-center cohort analysis, women with a singleton term pregnancy in the beginning stages of labor were included. Women with immediately antepartum EFW (N = 492) were compared to women without ultrasound (N = 515). RESULTS: EFW was correct (deviation from birth weight ≤ 10%) in 72.2% (355/492) of patients with fetal biometry; 19.7% (97/492) were underestimated, and 8.1% (40/492) were overestimated. Newborns with a lower birth weight were more frequently overestimated, and newborns with higher birth weight were more frequently underestimated. The mean difference between EFW and real birth weight was - 114.5 g (standard deviation ±313 g, 95% confidence interval 87.1-142.0). The rate of non-reassuring fetal heart tracing (9.8% vs. 1.9%, P < 0.001) and of caesarean delivery (9.1% vs. 5.0%, P = 0.013) was higher in women with EFW. Overestimation was associated with an increased risk for delivery by caesarean section (odds ratio 2.80; 95% confidence interval 1.2-6.5, P = 0.017). After adjustment, EFW remained associated with increased non-reassuring fetal heart tracing (odds ratio 4.73; 95% confidence interval 2.3-9.6) and caesarean delivery (odds ratio 1.86; 95% confidence interval 1.1-3.1). The incidence of perineal tears of grade 3/4, shoulder dystocia, postnatal depression and neonatal acidosis did not differ between groups. CONCLUSIONS: Antepartum ultrasound-derived EFW does not improve maternal and fetal outcome and is therefore not recommended.


Subject(s)
Birth Weight , Delivery, Obstetric/statistics & numerical data , Fetal Weight , Ultrasonography , Acidosis/epidemiology , Adult , Cesarean Section/statistics & numerical data , Cohort Studies , Delivery, Obstetric/methods , Depression, Postpartum/epidemiology , Dystocia/epidemiology , Female , Fetal Distress/epidemiology , Humans , Infant, Newborn , Lacerations/epidemiology , Perineum/injuries , Peripartum Period , Predictive Value of Tests , Pregnancy , Young Adult
9.
Cell Physiol Biochem ; 42(1): 254-268, 2017.
Article in English | MEDLINE | ID: mdl-28535507

ABSTRACT

AIMS: Stem cell-based regenerative therapies for the treatment of ischemic myocardium are currently a subject of intensive investigation. A variety of cell populations have been demonstrated to be safe and to exert some positive effects in human Phase I and II clinical trials, however conclusive evidence of efficacy is still lacking. While the relevance of animal models for appropriate pre-clinical safety and efficacy testing with regard to application in Phase III studies continues to increase, concerns have been expressed regarding the validity of the mouse model to predict clinical results. Against the background that hundreds of preclinical studies have assessed the efficacy of numerous kinds of cell preparations - including pluripotent stem cells - for cardiac repair, we undertook a systematic re-evaluation of data from the mouse model, which initially paved the way for the first clinical trials in this field. METHODS AND RESULTS: A systematic literature screen was performed to identify publications reporting results of cardiac stem cell therapies for the treatment of myocardial ischemia in the mouse model. Only peer-reviewed and placebo-controlled studies using magnet resonance imaging (MRI) for left ventricular ejection fraction (LVEF) assessment were included. Experimental data from 21 studies involving 583 animals demonstrate a significant improvement in LVEF of 8.59%+/- 2.36; p=.012 (95% CI, 3.7-13.8) compared with control animals. CONCLUSION: The mouse is a valid model to evaluate the efficacy of cell-based advanced therapies for the treatment of ischemic myocardial damage. Further studies are required to understand the mechanisms underlying stem cell based improvement of cardiac function after ischemia.


Subject(s)
Myocardial Infarction/therapy , Stem Cell Transplantation , Animals , Cell- and Tissue-Based Therapy , Databases, Factual , Disease Models, Animal , Heart/physiopathology , Humans , Mice , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Regeneration , Ventricular Function, Left/physiology
10.
J Neurooncol ; 135(2): 391-402, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28755324

ABSTRACT

The potential impact of different radiological features of glioblastoma multiforme (GBM) on overall survival (OS) like tumor volume, peritumoral edema (PTE), necrosis volume, necrosis-tumor ratio (NTR) and edema-tumor ratio (ETR) is still very controversial. To determine the influence of volumetric data on OS und to compare different measuring techniques described in literature. We prospectively evaluated preoperative MR images from 30 patients harboring a primary supratentorial GBM. All patients received gross-total tumor resection followed by standard radiation and chemotherapy (temozolomide). By 3D semi-automated segmentation, we measured tumor volume, necrosis volume, PTE, postoperative residual tumor volume and calculated ETR, NTR and the extent of resection. After critical review of the existing literature we compared alternative measuring techniques with the gold standard of 3D segmentation. Statistical analysis showed a significant impact of the preoperative tumor and necrosis volumes on OS (p = 0.041, respectively p = 0.039). Furthermore, NTR also showed a significant association with OS (p = 0.005). Comparison of previously described measuring techniques and scorings with our results showed that no other technique is reliable and accurate enough as a predictive tool. The critical review of previously published studies revealed mainly inaccurate measurement techniques and patient selection as potential reasons for inconsistent results. Preoperatively measured necrosis volume and NTR are the most important radiological features of GBM with a strong influence on OS. No other measuring techniques are specific enough and comparable with 3D segmentation.


Subject(s)
Brain/diagnostic imaging , Glioblastoma/diagnostic imaging , Image Interpretation, Computer-Assisted , Magnetic Resonance Imaging , Supratentorial Neoplasms/diagnostic imaging , Tumor Burden , Aged , Brain/pathology , Combined Modality Therapy , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Female , Glioblastoma/pathology , Glioblastoma/therapy , Humans , Image Interpretation, Computer-Assisted/methods , Imaging, Three-Dimensional , Isocitrate Dehydrogenase/genetics , Male , Middle Aged , Necrosis/diagnostic imaging , Necrosis/pathology , Pattern Recognition, Automated , Prognosis , Prospective Studies , Supratentorial Neoplasms/pathology , Supratentorial Neoplasms/therapy , Survival Analysis , Tumor Suppressor Proteins/genetics
11.
J Oral Pathol Med ; 46(10): 911-920, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28677249

ABSTRACT

BACKGROUND: Uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium, but parameters of OED are unknown. METHODS: Mucosal nuclei were imaged in 34 toluidine blue-stained oral lesions with a commercial endomicroscopy. Histopathological diagnosis showed four biopsies in "dys-/neoplastic," 23 in "inflammatory," and seven in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count, and automated nuclear analysis were measured by area under ROC curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected. RESULTS: Best-performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=0.986) and 6-nearest neighborhood relation (AUC=0.896), and best parameters of nuclear polymorphism were the count of atypical nuclei (AUC=0.996) and compactness of nuclei (AUC=0.922). Excluding low-grade OED, nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% were seen for distances of 6-nearest neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=0.779 vs 0.687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased. CONCLUSIONS: Nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error.


Subject(s)
Carcinoma in Situ/pathology , Cell Nucleus/pathology , Mouth Neoplasms/pathology , Mouth/pathology , Aged , Aged, 80 and over , Automation , Endoscopy , Epithelium/pathology , Female , Humans , Image Processing, Computer-Assisted , Male , Microscopy , Middle Aged , Pilot Projects
12.
Palliat Med ; 31(9): 861-867, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28659011

ABSTRACT

BACKGROUND: A palliative approach is recommended in the care of Parkinson's disease patients; however, many patients only receive this care in the form of hospice at the end of life. Physician attitudes about palliative care have been shown to influence referrals for patients with chronic disease, and negative physician perceptions may affect early palliative referrals for Parkinson's disease patients. AIM: To use Social Exchange Theory to examine the association between neurologist-perceived costs and benefits of palliative care referral for Parkinson's disease patients and their reported referral practices. DESIGN: A cross-sectional survey study of neurologists. SETTING/PARTICIPANTS: A total of 62 neurologists recruited from the National Parkinson Foundation, the Medical Association of Georgia, and the American Academy of Neurology's clinician database. RESULTS: Participants reported significantly stronger endorsement of the rewards ( M = 3.34, SD = 0.37) of palliative care referrals than the costs ( M = 2.13, SD = 0.30; t(61) = -16.10, p < 0.0001). A Poisson regression found that perceived costs, perceived rewards, physician type, and the number of complementary clinicians in practice were significant predictors of palliative care referral. CONCLUSION: Physicians may be more likely to refer patients to non-terminal palliative care if (1) they work in interdisciplinary settings and/or (2) previous personal or patient experience with palliative care was positive. They may be less likely to refer if (1) they fear a loss of autonomy in patient care, (2) they are unaware of available programs, and/or (3) they believe they address palliative needs. Initiatives to educate neurologists on the benefits and availability of non-terminal palliative services could improve patient access to this care.


Subject(s)
Attitude of Health Personnel , Neurologists/psychology , Palliative Care/economics , Parkinson Disease/economics , Parkinson Disease/therapy , Referral and Consultation/economics , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , United States
13.
Biol Blood Marrow Transplant ; 22(4): 637-643, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26802322

ABSTRACT

The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P < .001) and low TNC cell count (P = .044) were identified as significant independent risk factors for graft rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT model.


Subject(s)
Bone Marrow Cells/radiation effects , Bone Marrow Transplantation/methods , Gamma Rays/therapeutic use , Graft Rejection/immunology , Graft vs Host Disease/immunology , Animals , Bone Marrow Cells/cytology , Bone Marrow Cells/immunology , Bone Marrow Transplantation/adverse effects , Cell Count , Cyclosporine/pharmacology , Dogs , Dose-Response Relationship, Radiation , Everolimus/pharmacology , Female , Graft Rejection/pathology , Graft Survival , Graft vs Host Disease/pathology , Graft vs Host Disease/prevention & control , HLA Antigens/genetics , HLA Antigens/immunology , Immunosuppressive Agents/pharmacology , Male , Models, Animal , Mycophenolic Acid/pharmacology , Retrospective Studies , Risk Factors , Transplantation Chimera , Transplantation Conditioning , Transplantation, Homologous , Whole-Body Irradiation
14.
J Neurooncol ; 126(3): 585-92, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26603163

ABSTRACT

There is a distinct diversity between the appearance of every glioblastoma multiforme (GBM) on pretreatment magnetic resonance imaging (MRI) with a potential impact on clinical outcome and survival of the patients. The object of this study was to determine the impact of 10 different single nucleotide polymorphisms (SNPs) on various volumetric parameters in patients harboring a GBM. We prospectively analyzed 20 steroid-naïve adult patients who had been treated for newly diagnosed GBM. The volumetry was performed using MRI with the help of a semiautomated quantitative software measuring contrast enhancing tumor volume including necrosis, central necrosis alone and peritumoral edema (PTE). We calculated ratios between the tumor volume and edema (ETR), respectively necrosis (NTR). SNP analysis was done using genomic DNA extracted from peripheral blood genotyped via PCR and sequencing. There was a strong correlation between tumor volume and PTE (p < 0.001), necrosis (p < 0.001) and NTR (p = 0.003). Age and sex had no influence on volumetric data. The Aquaporin 4-31G > A SNP had a significant influence on the ETR (p = 0.042) by decreasing the measured edema compared with the tumor volume. The Interleukin 8-251A > T SNP was significantly correlated with an increased tumor (p = 0.048), PTE (p = 0.033) and necrosis volume (p = 0.028). We found two SNPs with a distinct impact on pretreatment tumor characteristics, presenting a potential explanation for the individual diversity of GBM appearance on MRI and influence on survival.


Subject(s)
Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Glioblastoma/genetics , Glioblastoma/pathology , Polymorphism, Genetic/genetics , Adult , Aged , Aged, 80 and over , Brain Neoplasms/surgery , Female , Follow-Up Studies , Glioblastoma/surgery , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Necrosis , Neoplasm Grading , Preoperative Care , Prognosis , Prospective Studies , Tumor Burden
15.
J Soc Work End Life Palliat Care ; 12(1-2): 23-46, 2016.
Article in English | MEDLINE | ID: mdl-27143572

ABSTRACT

Little is known about end-of-life care for individuals with Alzheimer's disease and other dementias. Four case studies are presented, using data collected by qualitative interviews conducted with family caregivers who were closely involved with end-of-life care for relatives with dementia. The case studies are formatted in two pairs, with one reflecting two deaths occurring at home and the other pair representing two deaths in the nursing home. The cases reveal a range of end-of-life experiences, suggesting that there is not just one "good" path. The extent of care needed, the responsiveness of the individual, the health of the caregiver(s), and the residence and support situations, can all intersect in a variety of ways that make no one scenario the answer for all. Although most people say they would prefer to die at home, in some situations the nursing home can be a satisfactory choice, particularly if hospice is involved. These narrative case studies give the reader insight into the variety of the end-of-life experiences and suggest the environment should be considered as part of the care provision.


Subject(s)
Caregivers/psychology , Dementia/nursing , Family/psychology , Palliative Care/organization & administration , Terminal Care/organization & administration , Aged , Alzheimer Disease/nursing , Female , Homes for the Aged , Hospice Care/organization & administration , Humans , Interviews as Topic , Male , Middle Aged , Nursing Homes , Pilot Projects , Qualitative Research , Retrospective Studies
16.
J Gerontol Soc Work ; 59(7-8): 554-571, 2016.
Article in English | MEDLINE | ID: mdl-27749212

ABSTRACT

Social isolation has serious negative public health impacts for older adults. Survey data were collected at three resident-managed elder intentional neighborhoods in the United States (n = 59), to determine if these neighborhoods, each based on the cohousing model, promote development of social resources for their residents. Social resources were measured on three dimensions: social networks, neighborly support, and satisfaction with the neighborhood community. Respondents were White, mean age of 73.3 (range = 63-91), primarily female (76.3%), and generally had high levels of education and self-reported health. Almost half (47%) were never married/divorced and 37% were childless. Inclusion of neighborhood ties ameliorated risk of social isolation. Satisfaction with support and a variety of neighboring behaviors were reported. These neighborhoods are meeting the needs of a potentially at-risk population as an avenue to promote social resources and reduce social isolation. The implications for gerontological social workers include a role in helping to mobilize and support these types of neighborhoods as a way to encourage mutual support among older adults. With the increase in the aging population, such models of proactive interdependence and communal coping have the potential to lessen or delay the demands that socially isolated elders place on social workers.


Subject(s)
Interpersonal Relations , Residence Characteristics , Residential Facilities/standards , Social Isolation/psychology , Social Work/methods , Adaptation, Psychological , Aged , Aged, 80 and over , Aging/psychology , Female , Humans , Male , Middle Aged , Social Support , United States
17.
J Hepatol ; 61(3): 502-7, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24801414

ABSTRACT

BACKGROUND & AIMS: Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. METHODS: We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. RESULTS: 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, with baseline viral load mean 7.8 log IU/ml (±0.72) and ALT median 25 U/L (18.75-33). Duration of antiviral theraphy before birth was mean 58 days (±19) TDF and 53 (±14) lamivudine. Viral load declined by 3.64 log IU/ml (±0.9) TDF and 2.81 log IU/ml (±1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3% and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to 2% and 0% in TDF and lamivudine cohorts, compared with 20% in untreated. CONCLUSIONS: TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.


Subject(s)
Adenine/analogs & derivatives , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Hepatitis B/prevention & control , Hepatitis B/transmission , Organophosphonates/adverse effects , Organophosphonates/therapeutic use , Pregnancy Complications, Infectious/prevention & control , Adenine/adverse effects , Adenine/therapeutic use , Adult , Cohort Studies , Female , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Hepatitis B/drug therapy , Hepatitis B virus/physiology , Humans , Incidence , Lamivudine/adverse effects , Lamivudine/therapeutic use , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Outcome , Prospective Studies , Tenofovir , Time Factors , Treatment Outcome , Viral Load
18.
Dtsch Med Wochenschr ; 149(16): e67-e75, 2024 Aug.
Article in German | MEDLINE | ID: mdl-38977000

ABSTRACT

BACKGROUND: Doctors in German hospitals are critical of their working conditions. They complain about long working hours, inadequate remuneration for their work, poor training and development opportunities, and increasing time spent on administrative tasks. As these points of criticism are largely based on subjective perception, in the present study we documented in detail the workflows of physicians in a major regional hospital, determined the time taken for the workflows, and performed a statistical evaluation of the data. METHODS: Nine doctors from the specialties of internal medicine, surgery, and anesthesia/intensive care medicine were observed during their shifts for a total period of 216 hours at an urban hospital in Germany. All of the tasks performed by the doctors were recorded in an observation protocol. RESULTS: The time spent daily on documentation by doctors of all specialties was on average 93.1 ±â€Š23.4 minutes, accounting for 19.4 % of a doctor's working hours. The specialists who spent the longest period of time on documentation were internists (120.2 ±â€Š15.0 minutes; 25 %). During an eight-hour working day, computers were used on average for 123.5 ±â€Š44.4 minutes; surgeons spent the shortest period of time on computers (71.5 ±â€Š16.6 minutes). The direct patient-related work time (excluding the time spent on operations) was considerably lower (33.8 + 22.7 minutes; 7 %) than the time spent daily on documentation, increased to 80.7 ±â€Š62.9 minutes when the time expended on actual surgical tasks was taken into account, and was then similar to the time spent on documentation (93.1 minutes). DISCUSSION: This pilot study was the first to determine, in real time, the work processes of doctors from different specialties at a German hospital. We noted a disparity between administrative and patient-related tasks in the in-patient setting. Legal and economic requirements exert a negative impact on medical care. We need to develop strategies for effective utilization of medical resources and for ensuring a high standard of medical care.


Subject(s)
Documentation , Germany , Humans , Workload/legislation & jurisprudence , Internal Medicine , Physicians/legislation & jurisprudence , Workflow
19.
PLoS One ; 19(8): e0301304, 2024.
Article in English | MEDLINE | ID: mdl-39173016

ABSTRACT

INTRODUCTION: Patients with head and neck cancer (PwHNC) benefit from targeted exercise interventions: symptom relief, compensation for dysfunction, improvement in quality of life (QoL). Data on acceptance physical interventions in PwHNC are rare. The 'OSHO #94' trial investigates the short- and medium-term effects of individualized home exercise in PwHNC on QoL, physical activity and functionality. The study includes a feasibility phase (proof of concept) in order to evaluate the acceptance. Here we present the study protocol as well as the feasibility results. METHODS AND ANALYSIS: This prospective, multicentre, single-arm intervention study includes PwHNC ≥18 years of age in aftercare or palliative care with stable remission under immunotherapy. The study opened in January 01, 2021, with estimated completion by December 31, 2024. The PwHNC receive an individualized home exercise program consisting of mobilization, coordination, strengthening and stretching exercises. This should be carried out at least three times a week over 12 weeks for 15 to 30 minutes, supplemented by aerobic training two to three times a week for 30 minutes (intervention). Once weekly telephone calls with a physiotherapist are performed. Subsequently, there is a 12-week follow-up (FU) without exercise specifications/contact. Outcomes are measured before and after the intervention and following the FU. Primary outcome of the feasibility phase (n = 25) was the determination of the dropout rate during the intervention with a termination cut off if more than 30% PwHNC withdrew premature. The primary outcome of the OSHO #94' trial (N = 53) is the change in global QoL score from pre- to post-intervention (EORTC QLQ-C30). Secondary outcomes include clinical and patient-reported measures, training details as well as functional diagnostic data (e.g. level of physical activity, training frequency, flexibility, fall risk and aerobic performance). RESULTS: 25 PwHNC were enrolled onto the feasibility cohort. Only16% (4/25 patients) did not complete the study. Therefore, recruitment of PwHNC was continued. The dropout rate was adjusted from 30% (N = 60) to 20% (N = 53, calculated sample size n = 42 PwHNC and 20% (n = 11) to dropout). CONCLUSIONS: Individualized home exercise programs in PwHNC in aftercare seem feasible. Consequently, the aim is now to evaluate the short and medium-term effects of individualized home exercise.


Subject(s)
Exercise Therapy , Feasibility Studies , Head and Neck Neoplasms , Quality of Life , Humans , Head and Neck Neoplasms/therapy , Exercise Therapy/methods , Prospective Studies , Male , Female , Middle Aged , Aged , Exercise , Adult
20.
J Women Aging ; 24(3): 242-61, 2012.
Article in English | MEDLINE | ID: mdl-22757762

ABSTRACT

Approximately 52 million Americans provide informal (unpaid) care to a family member or friend who is disabled or ill. The most common informal caregiving relationship is that of an adult child providing assistance to an aging parent. This article describes a qualitative study examining how adult daughters between the ages of 50 and 65 become caregivers to their parent or parent-in-law. Data were collected through in-depth, face-to-face interviews with 15 female caregivers. Analysis revealed that assistance provided to parents was initiated by one or more triggering event, after which participants became caregivers in either an emergent or deliberate manner.


Subject(s)
Caregivers , Health Status , Parent-Child Relations , Aged , Aged, 80 and over , Female , Humans , Income , Middle Aged , Social Support
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