Learning curve and functional outcomes after laser enucleation of the prostate for benign prostate hyperplasia according to surgeon's caseload.

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.

CILIORETINAL ARTERIES INFLUENCE OPTIC NERVE HEAD, PERIPAPILLARY, AND MACULAR VESSEL DENSITIES IN HEALTHY EYES: An Optical Coherence Tomography Angiography Study.

BACKGROUND/PURPOSE: To analyze the influence of a cilioretinal artery (CRA) on macular and peripapillary vessel density in healthy eyes as measured using optical coherence tomography angiography. METHODS: A total of 83 eyes of 83 patients were included in this study. Optical coherence tomography angiography was performed using the RTVue XR Avanti with AngioVue (Optovue Inc). The macula was imaged with a 3 × 3-mm scan, whereas for the optic nerve head a 4.5 × 4.5-mm scan was taken. Optical coherence tomography angiography images of the optic nerve head were screened for the presence of a CRA. RESULTS: In 31 eyes, a CRA was detected (37.3%). The vessel density in eyes with a CRA was significantly lower within the optic nerve head (P = 0.005) but higher in the peripapillary capillary network (P < 0.001) and (whole en face) macular superficial capillary plexus (P = 0.025), when compared with eyes with no CRA. CONCLUSION: Our findings reveal that in eyes with a CRA, the vessel density in the peripapillary and macular superficial capillary plexus is increased, whereas the optic nerve head perfusion (as indicated by vessel density in the inside disk region) is decreased. This has to be considered when analyzing quantitative optical coherence tomography angiography parameters in scientific and clinical applications.

Impact of integrated multiple image averaging on OCT angiography image quality and quantitative parameters.

PURPOSE: Multiple image averaging (MIA) is a new approach to improve OCT angiography (OCTA) imaging. The aim of this work was to analyze the impact of MIA on image quality and quantitative OCTA parameters. METHODS: Twenty eyes from 20 healthy volunteers (55.65 ± 14.8 years) were prospectively enrolled. Imaging was performed using two commercially available OCTA devices (Canon OCT HS-100, Optovue AngioVue) using a uniform imaging protocol. Each participant had two single scans of the macula (3 × 3mm, Canon and Optovue) as well as five continuous single scan imaging procedures (3 × 3mm each) using the Canon device. Three out of five of these images with highest quality were manually chosen and then automatically processed by the Canon device using MIA. The superficial retinal plexus of the single scans and of MIA images was analyzed with regard to the device' own image quality scores (IQS), peak signal-to-noise ratio (PSNR), the size of the foveolar avascular zone (FAZ), and vessel density (VD). Image acquisition times were recorded. Parameters were compared between the devices and the different imaging protocols. RESULTS: Average acquisition time was significantly higher for the MIA compared with the single measurements (29.09 ± 10.19 seconds (s) (MIA) vs. 5.56 ± 2.17 s (Canon single scan) vs. 20.28 ± 6.81 s (Optovue) (p < 0.001)). IQS showed no significant differences between the devices and between the recording protocols. PSNR was 12.38 ± 0.20 (Canon single scan), 13.01 ± 0.36 (Canon MIA), and 14.34 ± 0.60 (Optovue) (p < 0.001 between the groups). Mean FAZ area in Canon single scans was 0.29 ± 0.06 mm2, 0.27 ± 0.07 mm2 using MIA, and 0.27 ± 0.08 mm2 using the Optovue device. There was no significant difference between mean FAZ measurements before and after averaging (Canon single scan vs. MIA, p = 0.168). VD of the parafoveal area using MIA was significantly lower compared with both single scans (p < 0.001). CONCLUSIONS: MIA can improve PSNR, but it also reduces imaging speed and significantly affects VD measurements. Therefore, when comparing OCTA data, the use of uniform imaging protocols is required.

Optical Coherence Tomography Angiography Offers New Insights into Choriocapillaris Perfusion.

The choriocapillaris (CC) represents a fundamentally important vascular layer that is subject to physiologic changes with increasing age and that is also associated with a wide range of chorioretinal diseases. So far, information on blood flow in this specific layer has remained limited. With the advent of optical coherence tomography angiography (OCTA), new perspectives and possibilities of CC imaging have begun to evolve. This article shall review the opportunities and challenges of applying OCTA technology to the CC layer and summarize the current clinical efforts in OCTA CC imaging exemplarily in dry age-related macular degeneration and central serous chorioretinopathy.

Comparison of Choriocapillaris Flow Measurements between Two Optical Coherence Tomography Angiography Devices.

PURPOSE: To evaluate choriocapillaris (CC) perfusion in healthy subjects using 2 different optical coherence tomography angiography (OCT-A) devices. PROCEDURES: Macular OCT-A imaging (36 eyes of 36 subjects) was performed using Optovue AngioVue and Zeiss AngioPlex devices. CC decorrelation signal index was assessed, and CC data were analyzed regarding intra-device variability, inter-device correlation, age, signal strength, and fields of view. RESULTS: The intra-device variability of CC measurements in the 3 × 3 mm2 field was 5.3 and 2.6% (Angiovue and Angioplex, coefficients of variation; 6 × 6 mm2: 8.0 and 2.8%, respectively). Mean CC decorrelation signal index in 3 × 3 mm2 was 104.3 ± 6.7 (Angiovue) and 81.3 ± 9.2 (Angioplex) (6 × 6 mm2: 95.6 ± 8.1, 81.1 ± 6.5) with high correlation between both devices (3 × 3 mm2: p = 0.0053; 6 × 6 mm2: p = 0.0139). CC decorrelation signal index in 3 × 3 mm2 was significantly higher in subjects aged ≤58 years compared to subjects aged ≥59 years (Angiovue: 107.3 ± 3.6, 101.3 ± 7.7, p = 0.0156; Angioplex: 84.6 ± 7.6, 78.0 ± 9.5, p = 0.0371). Signal strength was 64.6 ± 8.9 (Angiovue) and 9.5 ± 0.8 (Angioplex). CONCLUSION: Both devices showed low intra-device variability and a high inter-device correlation. CC decorrelation signal index was negatively correlated with advancing age.

Embodiment of action-related language in the native and a late foreign language - An fMRI-study.

Theories of embodied cognition postulate that language processing activates similar sensory-motor structures as when interacting with the environment. Only little is known about the neural substrate of embodiment in a foreign language (L2) as compared to the mother tongue (L1). In this fMRI study, we investigated embodiment of motor and non-motor action verbs in L1 and L2 including 31 late bilinguals. Half had German as L1 and French as L2, and the other half vice-versa. We collapsed across languages to avoid the confound between language and order of language acquisition. Region of interest analyses showed stronger activation in motor regions during L2 than during L1 processing, independently of the motor-relatedness of the verbs. Moreover, a stronger involvement of motor regions for motor-related as compared to non-motor-related verbs, similarly for L1 and L2, was found. Overall, the similarity between L1 and L2 embodiment seems to depend on individual and contextual factors.

The impact of motion artifacts on quantitative optical coherence tomography angiography analysis in Parkinson's disease.

We have previously shown that OCTA imaging in PD patients can be challenging. Our data suggest that retinal perfusion is reduced in both plexuses in PD, which may serve as a noninvasive biomarker in the future. Yet, control of motion artifacts in OCTA measurements is critical in this motor-impaired cohort.

Longitudinal choriocapillaris changes in the presence of reticular pseudodrusen.

To determine longitudinal changes in choriocapillaris (CC) measures in eyes with reticular pseudodrusen (RPD) using optical coherence tomography angiography (OCTA). In this observational prospective study, 20 patients with exclusively RPD and no other alteration due to age-related macular degeneration were included. Eight RPD patients were re-examined at 5-year follow-up. Multimodal imaging was performed at baseline and at 5-year follow-up. OCTA CC images were analyzed for number, size and total area of flow deficits (FD), mean signal intensity, signal intensity standard deviation and kurtosis of signal intensity distribution in the ring area between a circle of 4 mm diameter and a circle of 6 mm diameter and in the superior ring quadrant. Area affected by RPD increased from 19.36 ± 8.39 mm2 at baseline to 37.77 ± 9.03 mm2 at 5-year follow-up. At baseline, percent of CC FD area was greater in RPD eyes (quadrant: p < 0.001; ring: p < 0.001) compared to controls. Besides, RPD eyes revealed a lower mean intensity signal (quadrant: p < 0.001; ring: p < 0.001). Evaluation of CC parameters suggested significant group × time interaction effects for CC FD (p = 0.04) and mean intensity signal (p = 0.004), in that RPD eyes presented increased CC FD and decreased mean intensity signal at follow-up. OCTA CC decorrelation signal further decreases in RPD patients over 5 years in both RPD-affected and RPD-unaffected macular areas.

Applicability of optical coherence tomography angiography (OCTA) imaging in Parkinson's disease.

To evaluate the significance of motion artifacts in optical coherence tomography angiography (OCTA) images of patients with Parkinson's disease (PD) and healthy controls. In this prospective, cross-sectional study subjects with medicated PD (ON) and healthy, age- and gender-matched volunteers were recruited. Participants underwent specific ophthalmological examinations, including OCTA. Angiograms of the superficial retinal capillary plexus were evaluated for the type and frequency of artifacts using a validated motion artifact score (MAS). A total of 30 PD patients (60 eyes), average disease duration of 9.61 ± 5.55 years, and 30 matched, healthy controls (60 eyes) were recruited. Twenty percent of all eyes had an eye disease, unknown to the participant, with a significant impact on OCTA results. After cleansing the dataset by excluding subjects with confounding ocular comorbidities 42 eyes of 28 PD patients and 53 eyes of 29 healthy controls were further evaluated. Overall MAS and all five subtypes of motion artifacts were comparable without significant differences between groups. OCTA can be used in treated PD patients (ON) without a significant increase in motion artifacts. Nevertheless, special attention should be paid to image quality during the acquisition of OCTA data, for which an experienced OCTA operator is useful.

Communication skills training in oncology: a position paper based on a consensus meeting among European experts in 2009.

BACKGROUND: Communication in cancer care has become a major topic of interest. Since there is evidence that ineffective communication affects both patients and oncology clinicians (physicians and nurses), so-called communication skills trainings (CSTs) have been developed over the last decade. While these trainings have been demonstrated to be effective, there is an important heterogeneity with regard to implementation and with regard to evidence of different aspects of CST. METHODS: In order to review and discuss the scientific literature on CST in oncology and to formulate recommendations, the Swiss Cancer League has organised a consensus meeting with European opinion leaders and experts in the field of CST, as well as oncology clinicians, representatives of oncology societies and patient organisations. On the basis of a systematic review and a meta-analysis, recommendations have been developed and agreed upon. RESULTS: Recommendations address (i) the setting, objectives and participants of CST, (ii) its content and pedagogic tools, (iii) organisational aspects, (iv) outcome and (v) future directions and research. CONCLUSION: This consensus meeting, on the basis of European expert opinions and a systematic review and meta-analysis, defines key elements for the current provision and future development and evaluation of CST in oncology.

Combining gemcitabine, oxaliplatin and capecitabine (GEMOXEL) for patients with advanced pancreatic carcinoma (APC): a phase I/II trial.

BACKGROUND: Gemcitabine remains the mainstay of palliative treatment of advanced pancreatic carcinoma (APC). Adding capecitabine or a platinum derivative each significantly prolonged survival in recent meta-analyses. The purpose of this study was to determine dose, safety and preliminary efficacy of a first-line regimen combining all three classes of active cytotoxic drugs in APC. PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced or metastatic, histologically proven adenocarcinoma of the pancreas were treated with a 21-day regimen of gemcitabine [1000 mg/m² day (d) 1, d8], escalating doses of oxaliplatin (80-130 mg/m² d1) and capecitabine (650-800 mg/m² b.i.d. d1-d14). The recommended dose (RD), determined in the phase I part of the study by interpatient dose escalation in cohorts of three to six patients, was further studied in a two-stage phase II part with the primary end point of response rate by RECIST criteria. RESULTS: Forty-five patients were treated with a total of 203 treatment cycles. Thrombocytopenia and diarrhea were the toxic effects limiting the dose to an RD of gemcitabine 1000 mg/m² d1, d8; oxaliplatin 130 mg/m² d1 and capecitabine 650 mg/m² b.i.d. d1-14. Central independent radiological review showed partial remissions in 41% [95% confidence interval (CI) 26% to 56%] of patients and disease stabilization in 37% (95% CI 22% to 52%) of patients. CONCLUSION: This triple combination is feasible and, by far, met the predefined efficacy criteria warranting further investigations.

Optical coherence tomography angiography image quality assessment at varying retinal expertise levels.

PURPOSE: To compare optical coherence tomography angiography (OCT-A) image quality gradings performed by readers of varying retinal expertise levels in different retinal diseases. METHODS: Central 3 × 3 mm2 OCT-A images (AngioVue, Optovue) of 57 healthy controls (50.9 ± 22.4 years) and 148 patients (66.5 ± 14.1 years) affected by various chorioretinal diseases were retrospectively analyzed including early age-related macular degeneration (AMD, n = 26), neovascular AMD (nAMD, n = 22), and geographic atrophy due to AMD (GA, n = 6), glaucoma (n = 28), central serous chorioretinopathy (CSC, n = 14), epiretinal membrane (EM, n = 26), retinitis pigmentosa (RP, n = 16), and retinal venous occlusion (RVO, n = 10). A senior expert in medical retina (SE), an ophthalmology resident (OR), and a non-ophthalmologic medical doctor (MD) independently assessed OCT-A image quality using the motion artifact score (MAS) and the segmentation accuracy score (SAS). RESULTS: Regarding MAS, inter-reader agreement between SE and OR was 93.7% (Cohen's kappa = 0.907) and 85.4% (Cohen's kappa = 0.786) between SE and MD. Regarding SAS, inter-reader agreement between SE and OR was 95.1% (Cohen's kappa = 0.92) and 92.2% (Cohen's kappa = 0.874) between SE and MD. In the SAS analysis, signal strength index (SSI) and presence of retinal pathology had a significant influence on the overall agreement (P = 0.046; P < 0.001). CONCLUSIONS: OCT-A image quality assessment can be performed most reliably by an ophthalmologist with knowledge in retinal image analysis. Yet, well-instructed non-ophthalmologic assessors show only slightly inferior results and, thus, may be integrated in routine OCT-A image quality assessment as well.

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.

Hepatitis C virus infection and outcome of renal transplantation.

Chronic hepatitis B and C viruses (HBV and HCV) are common problems in renal transplant patients. There is no uniform agreement regarding their influence on graft outcomes and patient survival. We evaluated the influence of anti-HCV and hepatitis B surface antigen-positive status; gender; age>49 years at the time of transplantation; alanine aminotransferase elevation; acute rejection; type of graft; number of transplants; and maintenance/induction immunosuppressive treatment on both graft and patient survivals among a population transplanted in our center between 1991 and 2004. Univariate analysis showed that anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. Over the age of 49 years at the time of transplantation, anti-HCV-positive status, cadaveric donor, kidney-pancreas transplantation, and three-drug immunosuppressive therapy were associated with diminished patient survival. Upon multivariate analysis, reduced patient survival was associated with the same variables as in the univariate analysis: anti-HCV-positive status, three-drug immunosuppressive therapy, and one or more episodes of acute rejection were associated with diminished graft survival. In our experience, anti-HCV-positive compared with anti-HCV-negative status was associated with a reduced graft (56% vs. 75%; P=.0002) and patient survival (68% vs. 83%; P=.0028).

Information Theory Broadens the Spectrum of Molecular Ecology and Evolution.

Information or entropy analysis of diversity is used extensively in community ecology, and has recently been exploited for prediction and analysis in molecular ecology and evolution. Information measures belong to a spectrum (or q profile) of measures whose contrasting properties provide a rich summary of diversity, including allelic richness (q=0), Shannon information (q=1), and heterozygosity (q=2). We present the merits of information measures for describing and forecasting molecular variation within and among groups, comparing forecasts with data, and evaluating underlying processes such as dispersal. Importantly, information measures directly link causal processes and divergence outcomes, have straightforward relationship to allele frequency differences (including monotonicity that q=2 lacks), and show additivity across hierarchical layers such as ecology, behaviour, cellular processes, and nongenetic inheritance.

The modified Dunn procedure for slipped capital femoral epiphysis: the Bernese experience.

PURPOSE: Based on previous investigations on the vascular blood supply to the femoral head, a technique for anatomical reduction after slipped capital femoral epiphysis was developed. This technique is a modification of the original technique by Dunn using a retinacular soft-tissue flap. This allows the visual control of the epiphyseal vascular blood supply. We report the experience at the inventor's institution with a critical discussion of the available literature. METHODS: Using a trochanteric osteotomy for surgical dislocation of the hip, a retinacular soft tissue flap is created containing the deep branch of the medial femoral circumflex artery, the external rotators and the capsule. The femoral epiphysis can be mobilised safely and reduced on the femoral neck after resection of the almost constantly present reactive metaphyseal callus. RESULTS: In our institution, the rate of avascular necrosis with 2% is comparably low to Dunn's original results. It is only present in cases where no bleeding was already evident before reduction of the epiphysis. The ten-year long-term results are favorable in these cases with a good functional result and only little progression of osteoarthritis. However, other authors have reported higher rates of avascular necrosis up to 24% in their initial experience. CONCLUSIONS: In experienced hands using the correct meticulous surgical technique, the results are favorable regarding the rates of avascular necrosis, the functional outcome and the development of radiographic osteoarthritis - even in acute and severe cases. Avascular necrosis is rare but can be observed if there is no evidence of intra-operative femoral head perfusion before and after reduction of the epiphysis.

Randomized trial showing equivalent efficacy of filgrastim 5 micrograms/kg/d and 10 micrograms/kg/d following high-dose chemotherapy and autologous bone marrow transplantation in high-risk lymphomas.

PURPOSE: To evaluate the effect of two filgrastim dosages after autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Eighty-six patients were enrolled onto a multicenter, randomized, open-label study. The study compared the efficacy and safety of two different doses of filgrastim, 5-microgram/kg/d subcutaneous (SC) bolus injection and 10-microgram/kg/d SC continuous infusion, starting on day 1 following ABMT. RESULTS: Both patient groups were well matched in terms of demography and disease. The results showed no statistical difference in the median time to reach an absolute neutrophil count (ANC) of 0.5 x 10(9)/L (11 days; P = .685) and no difference in the median duration of neutropenia (10 v 11 days, respectively; P = .567) between either dose of filgrastim. The incidence and duration of fever and neutropenic fever were the same in both groups. The number and mean duration of clinically and documented infections, duration of intravenous (IV) antibiotics, time to discharge from hospital, and tumor response also were similar in both groups. CONCLUSION: This study demonstrates that a dose of filgrastim 5 micrograms/kg/d administered as a daily SC bolus injection has a similar efficacy and safety profile compared with the 10-microgram/kg/d dose administered as a SC continuous infusion. The lower dose of filgrastim has potential cost-saving implications in terms of both the dose of drug administered and the ease of administration. Based on these findings, the recommended dose of filgrastim after ABMT should be 5 micrograms/kg/d.

Randomized study of recombinant human granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies.

PURPOSE: The aim of this prospective randomized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Patients with poor-risk non-Hodgkin's lymphoma or relapsed Hodgkin's disease were treated in a randomized, open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT. Of 43 assessable patients, 19 were randomized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d, 10 to filgrastim 20 micrograms/kg/d, and 14 to a parallel control group that received no filgrastim after ABMT. RESULTS: For all filgrastim-treated patients analyzed together, the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients (P = .0001). The median number of platelet transfusions was identical in both groups. Clinical parameters, including the median number of days with fever (1 v 4, P = .0418) and neutropenic fever (5 v 13.5, P = .0001) were significantly shorter in the filgrastim than in the control group. The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups; however, the differences did not reach statistical significance. For patients treated with the two different dose levels of filgrastim, the neutrophil recovery and clinical results were similar. Filgrastim-associated toxicity appeared to be minimal, with five adverse events considered at least possibly related to filgrastim: two in the higher-dose group and three in the lower-dose group. All of these were rated moderate, except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose. Survival and relapse-free survival were similar for control and filgrastim-treated patients. CONCLUSION: Taken together, the results of this first randomized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery, as well as in reducing treatment-related morbidity and overall duration of the treatment procedure.