Risk factors for serious infections in ANCA-associated vasculitis.

OBJECTIVES: Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial. METHODS: Data on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models. RESULTS: Eighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA. CONCLUSIONS: The use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.

Probiotic vs. placebo and metformin: probiotic dietary intervention in polycystic ovary syndrome - A randomized controlled trial.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as metformin, however both treatments are limited to specific symptoms and have common side effects. METHODS: This phase IV study is a monocentric, double blinded randomized clinical trial comparing the effects of six months of probiotic intervention to a placebo, with an additional open-label metformin arm as a positive control in a total of 180 participants with PCOS. The first of three visits is the screening visit, where inclusion/exclusion criteria are assessed. At the first visit, they are randomised into one of the three treatment arms equally and receive their study medication. After six months, all assessments from the first two visits are repeated. The primary endpoint is the change in free testosterone levels after the intervention, while secondary endpoints include changes in hormonal and metabolic parameters associated with PCOS as well as the gut microbial composition and diversity after intervention. DISCUSSION: Based on new insights into the role of the gut microbiome in PCOS development, this study is exploring the potential of using probiotics to treat women with PCOS symptoms. If successful, this new therapy approach could open a new realm of possibilities for treating PCOS. To our knowledge, this is the first study comparing probiotic intervention with not only placebo treatment, but also metformin. This study has been approved by the ethics committee of the Medical University of Graz (EC number 32-230 ex 19/20). REGISTRATION: EudraCT number: 2020-000228-20. CLINICALTRIALS: gov identifier: NCT04593459. PROTOCOL VERSION: Version 1.5 dated 29th November 2021.

Idebenone Treatment in Patients with OPA1-Dominant Optic Atrophy: A Prospective Phase 2 Trial.

The aim of this study was to evaluate the therapeutic effect of idebenone in patients with OPA1-dominant optic atrophy (DOA). Sixteen patients with genetically confirmed OPA1-DOA were treated with 900 mg idebenone daily for 12 months. The primary endpoint was the best recovery/least deterioration of visual acuity. Secondary endpoints were the changes of visual acuity, colour vision, contrast sensitivity, visual field, peripapillary retinal nerve fibre layer thickness (pRNFLT), and visual-related quality of life. For the primary endpoint, a significant increase was observed for the right eye (p = .0027), for the left eye (p = .0111) and for the better-seeing eye (p = .0152). For visual fields, a significant improvement was observed for the left eye between baseline and 9 months (p = .0038). Regarding pRNFLT, a significant decrease was found for the left eye between baseline and 3 months (p = .0413) and between baseline and 6 months (p = .0448). In the visual function questionnaire, a significant improvement was observed in the subscale general vision (p = .0156) and in the composite score (p = .0256). In conclusion, best recovery of visual acuity improved, even though the amount of improvement was small. Furthermore, a maintenance of visual function after 12 months of idebenone intake could be observed as well as a significant improvement in vision-related quality of life.Whether this effect is due to idebenone treatment, the placebo effect, or is explainable by the natural progression of DOA, remains unclear. Trial registration: EU Clinical Trials Register, EudraCT Number: 2019-001493-28.

Cotinine and cytokine levels in the vitreous body and blood serum of smokers and non-smokers - A pilot study.

Tobacco smoking is a risk factor for many ocular diseases. Of the multiple tobacco smoke compounds nicotine and its main metabolite cotinine are likely agents in disease modulation. The interaction of these compounds with exposed tissue is complex and ranges from proinflammatory to potentially neuroprotective properties. We aimed to determine cotinine and cytokines in the vitreous in smokers and non-smokers in this prospective, cross-sectional study at the Department of Ophthalmology, Medical University Graz, Austria. We included 10 smokers and 10 non-smokers. Vitreous and serum samples were analyzed for cotinine and cytokines. The cytokine analysis was performed with multiplex assay and cotinine was quantified with enzyme-linked immunosorbent assay. Cotinine was detectable in smokers only with a mean of 154.0 ng/ml ± 107.3 ng/ml in the vitreous and of 194.1 ng/ml ± 121.3 ng/ml in the serum. The difference between intraocular and systemic levels was statistically significant. There were no statistically significant differences between the cytokine levels of smokers and non-smokers. However, intravitreal VEGF-A was by trend elevated in smokers and correlated positively with intravitreal cotinine (r = 0.59, p = 0.073). In conclusion cotinine is detectable in the vitreous of smokers and is lower than the serum. There is a trend towards elevation of VEGF-A in the vitreous of smokers.

Bicycle spiroergometry: comparison of standardized examination protocols for adolescents: is it necessary to define own standard values for each protocol?

PURPOSE: To compare performance data of adolescents collected with five different bicycle spiroergometry protocols and to assess the necessity for establishing standard values for each protocol. METHODS: One-hundred-twenty adolescents completed two bicycle spiroergometries within 14 days. One of the two tests was performed based on our institutional weight-adapted protocol (P0). The other test was performed based on one out of four exercise protocols widely used for children and adolescents (P1, 2, 3 or 4) with 30 persons each. The two tests were performed in a random order. Routine parameters of cardiopulmonary exercise tests (CPET) such as VO2peak, maximum power, O2 pulse, OUES, VE/VCO2 slope as well as ventilatory and lactate thresholds were investigated. Agreement between protocols was evaluated by Bland-Altman analysis, coefficients of variation (CV) and intra-class correlation coefficients (ICC). RESULTS: None of the CPET parameters were significantly different between P0 and P1, 2, 3 or 4. For most of the parameters, low biases between P0 and P1-P4 were found and 95% confidence intervalls were narrow. CV and ICC values largely corresponded to well-defined analytical goals (CV < 10% and ICC > 0.9). Only maximal power (Pmax) showed differences in size and drift of the bias depending on the length of the step duration of the protocols. CONCLUSION: Comparability between examination protocols has been shown for CPET parameters independent on step duration. Protocol-dependent standard values do not appear to be necessary. Only Pmax is dependent on the step duration, but in most cases, this has no significant influence on the fitness assessment.

Long-Term Results after Suprapubic ARC Procedure for the Treatment of Stress Urinary Incontinence in Women: A Retrospective Data Analysis.

INTRODUCTION: The aim of this study was to evaluate long-term safety and efficacy of the suprapubic arc (SPARC) procedure for the surgical treatment of stress urinary incontinence (SUI). MATERIALS AND METHODS: 139 female patients treated by SPARC were included in this retrospective analysis, whereby 126 patients were available for follow-up after 1 year, 70 after 6 years, and 41 after 9 years. The cough test, pad test, uroflowmetry, and post-void residual volume measurements were performed. Severity of bother (visual analogous scale [VAS] 0-10), continence, and the satisfaction rate were assessed. Objective cure was defined as a negative cough test and pad weight ≤1 g, subjective cure as no urine loss during daily activities and no usage of pads. The VAS, pad weight, number of pads per day, and maximal flow rate were compared preoperatively and postoperatively. RESULTS: Objective cure rates at 1, 6, and 9 years were 78.6, 71.4, and 70.7% and subjective cure rates were 72.2, 55.7, and 65.8%, respectively. The VAS, pad weight, number of pads, and maximal flow rate decreased significantly. Study limitations include a relatively small sample size and the retrospective fashion of the analysis. CONCLUSIONS: In the long-term context, SPARC showed to represent an efficient and safe procedure for treatment of female SUI.

Malnutrition as predictor of poor outcome after total hip arthroplasty.

INTRODUCTION: The aim of this study was to assess the prevalence of protein energy malnutrition (PEM) and correlation with poor post-operative outcome in the elderly undergoing primary total hip arthroplasty (THA). HYPOTHESIS: Patients with PEM would have inferior post-operative outcome after THA. MATERIALS AND METHOD: We retrospectively evaluated the nutritional status of 220 hospitalized patients undergoing THA, 65 years and older. PEM was assessed using serum albumin and total lymphocyte count (TLC). Studied outcome parameters were length of pre-operative and post-operative stay, complications up to six months after surgery and 12-month mortality. Clinical and demographic data were retrieved from medical records from the hospital database. RESULTS: The prevalence of PEM among patients undergoing THA was 12.3% (27/220). Patients with PEM were significantly older (mean age 81.3 ± 7.0, p < 0.001), had a lower BMI (24.7 ± 4.1 kg/m 2, p = 0.022), and showed more comorbid conditions (mean CCI 2.8 ± 2.0, p = 0.002) compared with well-nourished patients (age 75.6 ± 6.2, BMI 26.8 ± 4.3 kg/m 2, CCI: 1.7 ± 1.7). Length of pre-operative stay differed significantly (p < 0.001) between PEM (median 7, range 1-36 days) and non PEM (median 1, range 1-22 days). In the PEM group, 12 (44.4%) patients had post-operative complications within six months after OP and 15 (7.8%) patients in the non PEM group (HR = 6.3, 95% CI 1.7-23.1). CONCLUSION: We observed a higher post-operative complication rate for malnourished patients undergoing elective THA. These results underline the importance of pre-operative nutritional assessment in the elderly. Therefore, serum albumin and TLC are valuable clinical markers of PEM and the post-operative outcome.

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study.

AIMS: To investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes. MATERIALS AND METHODS: This monocentric, open, single-arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic-hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later. RESULTS: While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry-based measurement of platelet surface activation markers showed hypoglycaemia-induced activation 24 hours (PAC1pos CD62Ppos , PAC1pos CD63Ppos and PAC1pos CD62Ppos CD63pos ; P < .01) and 7 days after the hypoglycaemic clamp (P < .001 for PAC1pos CD63pos ; P < .01 for PAC1pos CD62Ppos and PAC1pos CD62Ppos CD63pos ) in comparison to baseline. Coagulation markers, such as fibrinogen, D-dimer, plasminogen activator inhibitor-1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp. CONCLUSION: A single event of insulin-induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.

Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial.

BACKGROUND: Early glucose lowering intervention in subjects with type 2 diabetes mellitus was demonstrated to be beneficial in terms of micro- and macrovascular risk reduction. However, most of currently ongoing cardiovascular outcome trials are performed in subjects with manifest atherosclerosis and long-standing diabetes. Therefore, the aim of this study is to investigate the effects of the dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements. METHODS: In this randomized, placebo-controlled, double-blind, single-center study, we included subjects with early diabetes (postchallenge diabetes (2 h glucose > 200 mg/dl) or T2DM treated with diet only or on a stable dose of metformin monotherapy and an HbA1c < 75 mmol/mol) and established CAD. Participants were randomized to receive either linagliptin (5 mg) once daily orally or placebo for 12 weeks. The primary outcome was the change in flow mediated dilatation (FMD). The secondary objective was to investigate the effect of linagliptin treatment on arginine bioavailability ratios [Global arginine bioavailability ratio (GABR) and arginine to ornithine ratio (AOR)]. Arginine, ornithine and citrulline were measured in serum samples with a conventional usual amino acid analysis technique, involving separation of amino acids by ion exchange chromatography followed by postcolumn continuous reaction with ninhydrin. GABR was calculated by L-arginine divided by the sum of (L-ornithine plus L-citrulline). The AOR was calculated by dividing L-arginine by L-ornithine levels. Group comparisons were calculated by using a two-sample t-test with Satterthwaite adjustment for unequal variances. RESULTS: We investigated 43 patients (21% female) with a mean age of 63.3 ± 8.2 years. FMD at baseline was 3.5 ± 3.1% in the linagliptin group vs. 4.0 ± 2.9% in the placebo group. The change in mean FMD in the linagliptin group was not significantly different compared to the change in the placebo group (0.43 ± 4.84% vs. - 0.45 ± 3.01%; p = 0.486). No significant improvements were seen in the arginine bioavailability ratios (GABR; p = 0.608 and AOR; p = 0.549). CONCLUSION: Linagliptin treatment in subjects with CAD and early T2DM did not improve endothelial function or the arginine bioavailability ratios. Trial registration ClinicalTrials.gov, NCT02350478 ( https://clinicaltrials.gov/ct2/show/NCT02350478 ).

Decreased viability and proliferation of CHANG conjunctival epithelial cells after contact with ultraviolet light-irradiated pollen.

CONTEXT: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase. OBJECTIVE: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells. MATERIALS AND METHODS: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system. RESULTS: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen. DISCUSSION AND CONCLUSIONS: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

IMPORTANCE: Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE: To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS: A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS: Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES: The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS: A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE: Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130181.

Protective Effect of Amblyopia on Age-Related Macular Degeneration.

PURPOSE: Our aim was to evaluate whether patients with age-related macular degeneration (AMD) and cooccurrent amblyopia are more likely to have diseases diagnosed on both the ipsilateral and the contralateral side in a large Austrian database. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Institutional practice. PATIENT POPULATION: Medical records of all patients who visited the Department of Ophthalmology of the Medical University of Graz between December 1996 and June 2021 were searched for the co-occurrence of AMD and amblyopia. MAIN OUTCOME MEASURES: Data from patients with AMD diagnosed on 1 eye side were used for further analysis. Spectral-domain optical coherence tomography images were analyzed to confirm the lateral asymmetry of AMD. RESULTS: A total of 327,443 patients were screened for the co-occurrence of AMD and amblyopia. Of them, 8742 patients had AMD diagnosed on 1 eye side and 5051 patients had unilateral amblyopia. In total, 163 patients were found to have AMD diagnosed on 1 side and unilateral amblyopia in combination. Of these, 126 patients had AMD and amblyopia on contralateral sides and 37 had AMD and amblyopia on the ipsilateral side (P < .001). CONCLUSIONS: Less amblyopic patients had AMD diagnosed on the amblyopic eye compared with the nonamblyopic eye. In cases of lateral asymmetry, the nonamblyopic eye is more likely to have the more advanced form of AMD.

Progression of PROM1-Associated Retinal Degeneration as Determined by Spectral-Domain Optical Coherence Tomography Over a 24-Month Period.

PURPOSE: To evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed PROM1-associated retinal degeneration (RD) over a 24-month period. DESIGN: International, multicenter, prospective case series. METHODS: A total of 13 eyes (13 patients) affected with PROM1-associated RD were enrolled at 5 sites and SD-OCT images were obtained at baseline and after 24 months. Loss of mean thickness (MT) and intact area were estimated after semi-automated segmentation for the following individual retinal layers in the central subfield (CS), inner ring, and outer ring of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OS), inner segments (IS), outer nuclear layer (ONL), inner retina (IR), and total retina (TR). RESULTS: Statistically significant losses of thickness of RPE and TR were detected in the CS and inner ring and of ONL and IS in the outer ring (all P < .05); a statistically significant decrease in the intact area of RPE and IS was observed in the inner ring, and of ONL in the outer ring (all P < .05); the change in MT and the intact area of the other layers showed a trend of decline over an observational period of 24 months. CONCLUSIONS: Significant thickness losses could be detected in outer retinal layers by SD-OCT over a 24-month period in patients with PROM1-associated retinal degeneration. Loss of thickness and/or intact area of such layers may serve as potential endpoints for clinical trials that aim to slow down the disease progression of PROM1-associated retinal degeneration.

Changes of individual retinal layer thickness post-uneventful cataract surgery determined by spectral-domain optical coherence tomography over a 3-months period.

Purpose: To evaluate retinal thickness changes of individual retinal layers using spectral-domain optical coherence tomography (SD-OCT) after uneventful cataract surgery over a 3-months period. Design: Prospective cohort study. Methods: 41 patients who underwent uneventful cataract surgery were included. Retinal SD-OCT images of both eyes were acquired preoperatively, 1 day after surgery as well as 1 month and 3 months postoperatively. Changes of retinal layer thickness were estimated after semi-automated segmentation for the following individual layers in the central subfield (CS, 1 mm) and inner ring (IR, 1-3 mm) of the early treatment diabetic retinopathy study (ETDRS) grid: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), RNFL-GCL-IPL complex, inner nuclear layer (INL), outer plexiform layer (OPL), INL-OPL complex, outer nuclear layer (ONL), inner retina layer (IRL) and the total retina (TR). Furthermore, a sub-analysis with exclusion of patients devoid CME and an analysis in regard of patient age, lens status of the fellow eye, best corrected visual acuity and duration of surgery was conducted. Results: This study found significant alterations in all analysed retinal layers except for the RNFL (p = 0.33) and the GCL (p = 0.06) in the central subfield and the INL-OPL complex (p = 0.07) in the inner ring over the 3-months period (all p < 0.05). Retinal thickness decreases on the first postoperative day, followed by a significant increase 1 month after surgery and subsequent reduction at 3 months following uneventful cataract surgery could be observed. Conclusion: These results assume the hypothesis that the apex of inflammatory response, characterized by an augmentation in the thickness of individual retinal layers, occurs around 1 month after uneventful cataract surgery, and subsequently experience a reduction in activity. Therefore, we suggest that additional therapy for cystoid macular edema does not have to be initiated as early as the first month in mild cases.

Are morphological criteria sufficient for the identification of circulating tumor cells in renal cancer?

BACKGROUND: Single circulating tumor cells (CTCs) or circulating tumor microemboli (CTMs) are potential biomarkers of renal cell cancer (RCC), however studies of CTCs/CTMs in RCC are limited. In this pilot study we aimed to evaluate a novel blood filtration technique suited for cytomorphological classification, immunocytochemical and molecular characterization of filtered, so called circulating non-hematologic cells (CNHCs) - putative CTCs/CTMs - in patients with RCC. METHODS: Blood of 40 patients with renal tumors was subjected to ScreenCell filtration. CNHCs were classified according to cytomorphological criteria. Immunocytochemical analysis was performed with antibodies against CD45, CD31 and carbonic anhydrase IX (CAIX, a RCC marker). DNA of selected CNHCs and respective primary tumors was analysed by array-CGH. RESULTS: CNHC-clusters with malignant or uncertain malignant cytomorphological features - putative CTMs - were negative for CD45, positive for CD31, while only 6% were CAIX positive. Array-CGH revealed that 83% of malignant and uncertain malignant cells did represent with a balanced genome whereas 17% presented genomic DNA imbalances which did not match the aberrations of the primary tumors. Putative single CTCs were negative for CD45, 33% were positive for CD31 and 56% were positive for CAIX. CONCLUSIONS: The majority of CNHC-clusters, putative CTMs, retrieved by ScreenCell filtration may be of endothelial origin. Morphological criteria seem to be insufficient to distinguish malignant from non-malignant cells in renal cancer.

Blood transfusions and the subsequent risk of cancers in the United States elderly.

BACKGROUND: Blood transfusions are common in older adults and also may modulate the immune system. However, the impact of transfusion on cancer risk in the elderly has not been studied. STUDY DESIGN AND METHODS: Cancer risk after blood transfusion was evaluated in a US population-based case-control study using 552,951 elderly cases identified from cancer registries and 100,000 frequency-matched controls. Transfusions received 0 to 12, 13 to 30, and 31 to 48 months before cancer diagnosis or selection date were identified using Medicare claims. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models. A Bonferroni correction adjusted for multiple testing. RESULTS: Transfusions received 0 to 12 months before cancer diagnosis and/or selection were associated with significantly elevated risk of cancer overall (OR,2.05; 95% CI, 1.95-2.16) and cancer of the stomach; cancer of the colon; cancer of the liver, kidney, renal pelvis, and/or ureter; lymphoma; myeloma; and leukemia. No significant associations for cancer overall were observed for the two earlier intervals. No site was associated with transfusions received 13 to 30 or 31 to 48 months before diagnosis and/or selection. Nonetheless, overall cancer risk increased with the number of transfused periods (p-trend<0.0001). CONCLUSION: Risk of overall cancer and specific sites was elevated 0 to 12 months after blood transfusion and associated with multiple transfusions, possibly due to reverse causation, that is, incipient cancers or cancer precursors causing anemia.

Fecal carriage and intrafamilial spread of extended-spectrum ß-lactamase-producing enterobacteriaceae following colonization at the neonatal ICU.

OBJECTIVE: Fecal carriage of extended-spectrum ß-lactamase-producing enterobacteriaceae may contribute to the spread of extended-spectrum ß-lactamase-producing enterobacteriaceae into the community. The objective of this study was to assess the duration of fecal carriage after discharge and the occurrence of intrafamilial transmission. DESIGN: Case series. SETTING: Quaternary care children's hospital. PATIENTS: Patients colonized with extended-spectrum ß-lactamase-producing enterobacteriaceae at the neonatal ICU and the respective household members. INTERVENTIONS: Screening for intestinal extended-spectrum ß-lactamase-producing enterobacteriaceae colonization was done at 1, 2, 4, 6, 9, and 12 months after discharge. Genetic relatedness of isolated extended-spectrum ß-lactamase-producing enterobacteriaceae strains was determined using automated rep-PCR. RESULTS: Twenty-five neonates (case-patients) colonized with extended-spectrum ß-lactamase-producing enterobacteriaceae (one extended-spectrum ß-lactamase-Escherichia coli; six extended-spectrum ß-lactamase-Klebsiella pneumoniae; 11 extended-spectrum ß-lactamase-Klebsiella oxytoca; and seven extended-spectrum ß-lactamase-Serratia marcescens) were included. Duration of fecal carriage was longer (up to 1 yr) in case-patients colonized with Klebsiella species than in case-patients colonized with Serratia marcescens (<4 months). During follow-up, strains and species of extended-spectrum ß-lactamase-producing enterobacteriaceae different from the primary strain were found in four and three case-patients, respectively. In nine of 49 (18.4%) included household members, extended-spectrum ß-lactamase-producing enterobacteriaceae were found during the follow-up period. In two of nine colonized household members, the isolated extended-spectrum ß-lactamase-producing enterobacteriaceae was identical to the primary strains of the respective case-patients. CONCLUSIONS: After intestinal colonization with extended-spectrum ß-lactamase-producing enterobacteriaceae at the neonatal ICU, infants potentially remain carriers during the first year after discharge. Intrafamilial spread has been proven.

Diagnostic value of two-time point [68Ga]Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer.

The emerging PET tracer [68Ga]Ga-PSMA-11 has been established for staging in prostate cancer (PCa). Aim was to determine the value of early static imaging in two-phase PET/CT. 100 men with newly diagnosed histopathologically confirmed untreated PCa who underwent [68Ga]Ga-PSMA-11 PET/CT from January 2017 to October 2019 were included. The two-phase imaging protocol consisted of an early static scan of the pelvis (6 min p.i.) and a late total-body scan (60 min p.i). Associations of semi-quantitative parameters derived via volumes of interest (VOI) with Gleason grade group and PSA were investigated. In 94/100 patients (94%) the primary tumor was detected in both phases. In 29/100 patients (29%) metastases were detected at a median PSA level of 32.2 ng/ml (0.41-503 ng/ml). In 71/100 patients (71%) without metastasis a median PSA level of 10.1 ng/ml (0.57-103 ng/ml) was observed (p = < 0.001). Primary tumors demonstrated a median standard uptake value maximum (SUVmax) of 8.2 (3.1-45.3) in early phase versus 12.2 (3.1-73.4) in late phase and a median standard uptake value mean (SUVmean) of 4.2 (1.6-24.1) in early phase versus 5.8 (1.6-39.9) in late phase, significantly increasing over time (p = < 0.001). Higher SUVmax and SUVmean were associated with higher Gleason grade group (p = 0.004 and p = 0.003, respectively) and higher PSA levels (p = < 0.001). In 13/100 patients the semi-quantitative parameters including SUVmax were declining in the late phase compared to early phase. Two-phase [68Ga]Ga-PSMA-11 PET/CT demonstrates a high detection rate for primary tumor of untreated PCa of 94% and improves diagnostic accuracy. Higher PSA levels and Gleason grade group are associated with higher semi-quantitative parameters in the primary tumor. Early imaging provides additional information in a small sub-group with declining semi-quantitative parameters in the late phase.

Evaluating a Periapical Lesion Detection CNN on a Clinically Representative CBCT Dataset-A Validation Study.

The aim of this validation study was to comprehensively evaluate the performance and generalization capability of a deep learning-based periapical lesion detection algorithm on a clinically representative cone-beam computed tomography (CBCT) dataset and test for non-inferiority. The evaluation involved 195 CBCT images of adult upper and lower jaws, where sensitivity and specificity metrics were calculated for all teeth, stratified by jaw, and stratified by tooth type. Furthermore, each lesion was assigned a periapical index score based on its size to enable a score-based evaluation. Non-inferiority tests were conducted with proportions of 90% for sensitivity and 82% for specificity. The algorithm achieved an overall sensitivity of 86.7% and a specificity of 84.3%. The non-inferiority test indicated the rejection of the null hypothesis for specificity but not for sensitivity. However, when excluding lesions with a periapical index score of one (i.e., very small lesions), the sensitivity improved to 90.4%. Despite the challenges posed by the dataset, the algorithm demonstrated promising results. Nevertheless, further improvements are needed to enhance the algorithm's robustness, particularly in detecting very small lesions and the handling of artifacts and outliers commonly encountered in real-world clinical scenarios.