HIV immunological non-responders are characterized by extensive immunosenescence and impaired lymphocyte cytokine production capacity.

Introduction: Immunological non-responders (INR) are people living with HIV (PLHIV) who fail to fully restore CD4+ T-cell counts despite complete viral suppression with antiretroviral therapy (ART). INR are at higher risk for non-HIV related morbidity and mortality. Previous research suggest persistent qualitative defects. Methods: The 2000HIV study (clinical trials NTC03994835) enrolled 1895 PLHIV, divided in a discovery and validation cohort. PLHIV with CD4 T-cell count <350 cells/mm3 after ≥2 years of suppressive ART were defined as INR and were compared to immunological responders (IR) with CD4 T-cell count >500 cells/mm3. Logistic and rank based regression were used to analyze clinical data, extensive innate and adaptive immunophenotyping, and ex vivo monocyte and lymphocyte cytokine production after stimulation with various stimuli. Results: The discovery cohort consisted of 62 INR and 1224 IR, the validation cohort of 26 INR and 243 IR. INR were older, had more advanced HIV disease before starting ART and had more frequently a history of non-AIDS related malignancy. INR had lower absolute CD4+ T-cell numbers in all subsets. Activated (HLA-DR+, CD38+) and exhausted (PD1+) subpopulations were proportionally increased in CD4 T-cells. Monocyte and granulocyte immunophenotypes were comparable. INR lymphocytes produced less IL-22, IFN-γ, IL-10 and IL-17 to stimuli. In contrast, monocyte cytokine production did not differ. The proportions of CD4+CD38+HLA-DR+ and CD4+PD1+ subpopulations showed an inversed correlation to lymphocyte cytokine production. Conclusions: INR compared to IR have hyperactivated and exhausted CD4+ T-cells in combination with lymphocyte functional impairment, while innate immune responses were comparable. Our data provide a rationale to consider the use of anti-PD1 therapy in INR.

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies.

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.

The 2000HIV study: Design, multi-omics methods and participant characteristics.

Background: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets. Methods: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort. Results: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine. Conclusion: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.

The role of routine follow-up visits of prostate cancer survivors in addressing supportive care and information needs: a qualitative observational study.

PURPOSE: To understand the role of routine follow-up visits in addressing prostate cancer survivors' supportive care and information needs. METHODS: We audio-recorded follow-up visits of 32 prostate cancer survivors. Follow-up visits were analyzed according to the Verona Network of Sequence Analysis. We categorized survivors' cues, concerns, and questions into five supportive care domains and divided the responses by the healthcare professionals into providing versus reducing space that is to determine whether or not the response invites the patient to talk more about the expressed cue or concern. RESULTS: Prostate cancer survivors mostly expressed cues, concerns, and questions (in the health system and information domain) about test results, potential impotence treatment, follow-up appointments, and (their) cancer treatment during follow-up visits. Survivors also expressed urinary complaints (physical and daily living domain) and worry about the recurrence of prostate cancer (psychological domain). Healthcare professionals were two times more likely to provide space on cues and concerns related to the physical and daily living domain than to psychological related issues. CONCLUSION: Follow-up visits can serve to address prostate cancer survivors' supportive care and information needs, especially on the health system, information, and physical and daily living domain. Survivors also expressed problems in the psychological domain, although healthcare professionals scarcely provided space to these issues. We would like to encourage clinicians to use these results to personalize follow-up care. Also, these data can be used to develop tailored (eHealth) interventions to address supportive care and information needs and to develop new models of survivorship care delivery.

Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial.

BACKGROUND: Adjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent. METHODS: In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I-III and IV-V). The primary outcome was LOS. RESULTS: Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0-5.0 days) than in the placebo group (5.0 days, 95% CI 4.6-5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent. CONCLUSION: Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk-benefit ratio is optimal.

EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer-An International Collaborative Multistakeholder Effort†: Under the Auspices of the EAU-ESMO Guidelines Committees.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. PATIENT SUMMARY: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Comparing viral load metrics and evaluating their use for HIV surveillance.

OBJECTIVES: To investigate the value of in-care viral load (ICVL) and other viral load (VL) metrics for HIV surveillance by comparing time trends and associations with numbers of new HIV diagnoses. METHODS: Data from 20,740 HIV patients registered in the Dutch ATHENA-cohort between 2002 and 2013 were used. We compared: six ICVL metrics (i.e. mean of the mean/first/last/highest log VL, median of the median log VL, first log VL for newly diagnosed combined with mean log VL for all others), log VL at diagnosis, proportion of patients with transmission risk (>400 copies/ml) or suppressed VL (≤200 copies/ml). Subgroup differences were assessed using Kruskal-Wallis and chi-square tests. Negative binomial regression was used for studying associations between VL metrics and numbers of new diagnoses 1-4 years later. RESULTS: Most ICVL metrics showed similar decreasing trends over time. Differences in covariables were found for all VL metrics. Mean ICVL showed the strongest association with new diagnoses: a decrease of one log unit in mean ICVL was associated with a 21% decrease in new diagnoses two years later. CONCLUSIONS: VL metrics may be of value for enhancing HIV surveillance by identifying subgroup differences in impact of treatment on viral suppression, and by predicting numbers of new diagnoses in subsequent years.

The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients.

Background. Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment-naive HIV-infected patients. Methods. In a randomized double-blind placebo-controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered. Results. T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P < .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found. Conclusions. Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp).

Comprehensive Geriatric Assessment and Transitional Care in Acutely Hospitalized Patients: The Transitional Care Bridge Randomized Clinical Trial.

IMPORTANCE: Older adults acutely hospitalized are at risk of disability. Trials on comprehensive geriatric assessment (CGA) and transitional care present inconsistent results. OBJECTIVE: To test whether an intervention of systematic CGA, followed by the transitional care bridge program, improved activities of daily living (ADLs) compared with systematic CGA alone. DESIGN, SETTING, AND PARTICIPANTS: This study was a double-blind, multicenter, randomized clinical trial conducted at 3 hospitals with affiliated home care organizations in the Netherlands between September 1, 2010, and March 1, 2014. In total, 1070 consecutive patients were eligible, 674 (63.0%) of whom enrolled. They were 65 years or older, acutely hospitalized to a medical ward for at least 48 hours with an Identification of Seniors at Risk-Hospitalized Patients score of 2 or higher, and randomized using permuted blocks stratified by study site and Mini-Mental State Examination score (<24 vs ≥24). The dates of the analysis were June 1, 2014, to November 15, 2014. INTERVENTIONS: The transitional care bridge program intervention was started during hospitalization by a visit from a community care registered nurse (CCRN) and continued after discharge with home visits at 2 days and at 2, 6, 12, and 24 weeks. The CCRNs applied the CGA care and treatment plan. MAIN OUTCOMES AND MEASURES: The main outcome was the Katz Index of ADL at 6 months compared with 2 weeks before admission. Secondary outcomes were mortality, cognitive functioning, time to hospital readmission, and the time to discharge from a nursing home. RESULTS: The study cohort comprised 674 participants. Their mean age was 80 years, 42.1% (n = 284) were male, and 39.2% (n = 264) were cognitively impaired at admission. Intent-to-treat analysis found no differences in the mean Katz Index of ADL at 6 months between the intervention arm (mean, 2.0; 95% CI, 1.8-2.2) and the CGA-only arm (mean, 1.9; 95% CI, 1.7-2.2). For secondary outcomes, there were 85 deaths (25.2%) in the intervention arm and 104 deaths (30.9%) in the CGA-only arm, resulting in a lower risk on the time to death within 6 months after hospital admission (hazard ratio, 0.75; 95% CI, 0.56-0.99; P = .045; number needed to treat to prevent 1 death, 16). No other secondary outcome was significant. CONCLUSIONS AND RELEVANCE: A systematic CGA, followed by the transitional care bridge program, showed no effect on ADL functioning in acutely hospitalized older patients. TRIAL REGISTRATION: Netherlands Trial Registry: NTR2384.

Stapling for prostate pedicle management during robot-assisted radical prostatectomy.

BACKGROUND: Prostate pedicle management is a crucial step during robot-assisted radical prostatectomy (RARP). Wide excision of prostate pedicle may be required to avoid positive surgical margins (PSMs) whereas preservation of neurovascular bundles requires resection close on the prostate. We studied Endo GIA™ stapling of prostate pedicle during RARP. METHODS: Retrospectively the outcome of 55 men who underwent RARP with Endo GIA™ stapling (45-mm Echelon Ethicon; group A) of the pedicle were compared with 100 men where another method for prostate pedicle management (mono- and bipolar electrocautery, Hem-o-Lock clips or titanium 10-mm clips; group B) was used. Both groups were matched for age, prostate size, clinical T-stage, Gleason Score and fascia preservation (FP) score (as a measure of nerve sparing). Surgical, oncological, functional outcome factors and costs were compared. RESULTS: The overall PSM rate was 33% in group A and 42% in group B (P=0.251). None of the cases had PSMs at the location of staples. PSMs with Endo GIA™ stapler at the periphery of the prostate were less frequent than in control group (4.1% vs. 11.5%; P=0.021). Median pedicle dissection time (7.8 [3.1-15.1] min vs. 10.5 [5.8-28.3] min; P=0.0001) and median operative time for RARP combined with lymphadenectomy (114 [70-129] min vs. 120 [67-200] min; P=0.043) tended to be shorter compared to group B. Erectile function and continence recovery at 12 months were comparable for both groups. Material costs for stapling (€730) were higher compared to variable costs in control group. CONCLUSIONS: Pedicle stapling during RARP reduced peripheral PSMs. It did not compromise functional results, provided a modest operation time gain for pedicle dissection, but is more expensive.

Enterocolic lymphocytic phlebitis: an oncologic surgical resection without a preoperative pathologic diagnosis.

A patient with complaints of an abdominal (mesenteric) mass is presented. Differential diagnosis included neoplastic processes, such as malignant lymphoma, desmoid tumour, a carcinoid or a gastro-intestinal stromal cell tumour. An oncological resection was performed. Despite the malignant appearance of the tumour no malignancy was found with histopathological examination. Vasculitic lesions were seen in venous structures, resembling veno-occlusive disease with signs of recanalization and with the presence of inflammatory cells, mainly lymphocytes. A diagnosis of enterocolic lymphocytic phlebitis was made. This benign condition can mimic malignancy, necessitating a wide excision, also because obtaining a pre-operative histopathological diagnosis is hardly possible.

Impact on quality of life of radical prostatectomy after initial active surveillance: more to lose?

OBJECTIVE: The aim of this study was to determine whether deferred radical therapy for low-risk prostate cancer has an additionally unfavourable effect on quality of life (QoL). Substantial numbers of patients on active surveillance (AS) are eventually treated. MATERIAL AND METHODS: Prostate cancer patients treated with robot-assisted radical prostatectomy (RARP) in the NCI-AvL (Amsterdam, The Netherlands) received systematic QoL questionnaires preoperatively and postoperatively. Questionnaires included the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core Module and Prostate Module (EORTC-QLQ-C30 and EORTC-QLQ-PR25), International Index of Erectile Function-15 (IIEF-15) and International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). Patients with low-risk prostate cancer who received RARP after an initial period of AS (AS-RARP group) were compared with similar patients who primarily elected surgery (direct-RARP group). RESULTS: The AS-RARP group included 29 patients who received RARP after a median period of 15.4 months of AS (range 3.0-18.8 months). Main reasons for deferred radical therapy were repeat biopsy risk reclassification (45%) and prostate-specific antigen progression (38%). The direct-RARP group included 363 patients treated after 3.3 months (range 0.1-45.5 months). RARP generally resulted in clinically relevant unfavourable changes on different QoL domains in both groups. Preoperatively the AS-RARP group showed more favourable scores on multiple QoL domains (physical functioning, p = 0.004; role functioning, p = 0.001; global health, p = 0.043; sexual activity, p = 0.001; sexual functioning, p = 0.029; IIEF-15, p = 0.042). Postoperatively, most of these more favourable scores in the AS-RARP group had changed to scores similar to the direct-RARP group, except for IIEF-15 (p = 0.027) and urinary symptoms (p = 0.001). When using a 12 month treatment delay threshold, a similar but less distinct effect was seen. CONCLUSIONS: Patients with low-risk prostate cancer who choose AS have more favourable preoperative QoL scores than patients who primarily elect radical prostatectomy, but these groups show similar postoperative QoL scores.

Quality of life in patients with low-risk prostate cancer. A comparative retrospective study: brachytherapy versus robot-assisted laparoscopic prostatectomy versus active surveillance.

PURPOSE: To investigate the quality of life (QoL) after different treatment modalities for low-risk prostate cancer, including brachytherapy, robot-assisted laparoscopic prostatectomy (RALP), and active surveillance (AS) with validated questionnaires. MATERIALS AND METHODS: From a prospective database, we selected a total of 144 men with low-grade localized prostate cancer including 65 (45.1%) patients with RALP, 29 (20.2%) with brachytherapy, and 50 (34.7%) whose cancer was managed with AS. QoL was routinely evaluated with validated questionnaires: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), EORTC-QLQ-Prostate Module (PR)25, International Index of Erectile Function (IIEF)-15, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) with a minimum follow-up of 1 year. RESULTS: In comparison with baseline scores, the brachytherapy group showed a significant decrease of QoL domain scores of voiding complaints (P=0.010), use of incontinence aids (P=0.011), sexual functioning domain (P=0.011), and erectile function (P≤0.001). In the RALP group, sexual function (P≤0.001), incontinence (P≤0.001), and erectile function were significantly affected. A decrease in sexual function was observed in 71% of men after RALP and 59% after brachytherapy. In 30% of men under AS, a decrease of erectile function score during follow-up was reported. Overall, no significant decrease in general QoL was observed neither for men under AS nor for men treated by brachytherapy or RALP. Clinical factors such as age, prostate size, prostate-specific antigen level, and nerve preservation during RALP were nonpredictive of overall QoL after treatment for the individual patient (P=0.676). CONCLUSION: Patients with low-risk prostate cancer who are treated with brachytherapy or RALP report deterioration of QoL of specific domains such as voiding, continence, and sexual functioning in comparison with AS patients. A decrease of erectile function was also observed during AS. Overall QoL was similar for all three treatments options.

Salvage radiotherapy after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVE: To assess the incidence and efficacy of salvage radiotherapy (SRT) after robot-assisted radical prostatectomy (RARP). RARP has been linked to an increased use of adjuvant treatments. If RARP would result in an increased local recurrence rate, response rates to SRT could be expected to be better after RARP than after more conventional methods of prostatectomy. The incidence and efficacy of SRT in a RARP population were compared with nomogram prediction. METHODS: Patient data were prospectively registered. Biochemical recurrence (BCR) was defined as a prostate-specific antigen (PSA) ≥0.1 ng/mL. SRT was offered to men with BCR after RARP. The Stephenson nomogram predictions were compared with outcome after SRT. RESULTS: Of 1087 men, 157 (14.4%) received SRT for BCR or persistent PSA levels during a median follow-up of 1078 days after RARP. Median PSA level before SRT was 0.2 ng/mL. Three-year BCR-free rate was 64% for men after SRT. pN (pNx, pN0, pN1) and PSA level before SRT were independent predictors of the BCR interval after SRT. Men with more extensive fascia preservation were more likely to respond favorably to SRT. The Stephenson nomogram prediction showed a concordance rate of 0.66 in this RARP population. Limitations of the study are the retrospective design and limited follow-up duration. CONCLUSION: In our RARP series, the use and efficacy of SRT were comparable with open prostatectomy series. The Stephenson nomogram reliably predicted outcome in patients with RARP with SRT, suggesting that similar characteristics predict response to SRT after RARP compared with open prostatectomy.

Interview-based versus questionnaire-based quality of life outcomes before and after prostatectomy.

INTRODUCTION: Functional outcome and quality of life (QOL) domains are important outcomes after curative therapy for prostate cancer. Although useful for scientific purposes, QOL questionnaires may be too extensive for daily routine, and single questions or interview-assessed outcomes may be more practical alternatives. The QOL outcomes of these measures were compared. MATERIALS AND METHODS: The QOL of patients undergoing Robot-Assisted Radical Prostatectomy (RARP) in our hospital was monitored before and after treatment using both brief standardized interview questions, as well as more extensive validated questionnaires. The interview questions address erectile function and urinary continence with only one question on each subject (both four response items). Questionnaires included a total of 74 questions (EORTC-QLQ-C30, EORTC-QLQ-PR25, international index of erectile function-15, and international consultation on incontinence questionnaire-short form). RESULTS: In 925 RARP patients, pre- and postoperative interview and questionnaire QOL data were available with a median follow up of 20 months. Improvement in both erectile function and continence scores occurred up till 2 years after the RARP for both interview- and questionnaire-based evaluations. On an individual patient basis, interview scores poorly correlated with questionnaire-based domains for continence and erectile function. Single questions from the questionnaire showed better correlation with domain scores. Functional recovery of continence after 1 year was worse when assessed by questionnaire than by interview evaluation. A decrease in physical (8%) and overall QOL (12%) after prostatectomy as assessed by the EORTC-QLQ-C30 questionnaire was better predicted by questionnaire-based than interview-based scores. Continence scores had a greater impact on physical and overall QOL scores than on erectile function scores. CONCLUSION: Interview/assessed continence and erectile function outcome after RARP showed limited association with questionnaire-based evaluation and may overestimate functional recovery. Continence scores for both interviews and questionnaires were stronger correlated with physical and overall QOL than erectile function scores.

[Serious complications of urinary tract infection in diabetes: emphysematous pyelonephritis and endogenous endophthalmitis]. / Ernstige complicaties van urineweginfectie bij diabetes.

BACKGROUND: Patients with poorly regulated diabetes mellitus may develop severe infectious complications. In this article we describe a diabetic patient with urosepsis, complicated by emphysematous pyelonephritis and endogenous endophthalmitis. CASE DESCRIPTION: A 42-year-old diabetic woman presented with drowsiness and flank pain at the right side. She turned out to have diabetic ketoacidosis and urosepsis caused by Escherichia coli. Ultrasonography and CT scan of the abdomen showed subcapsulary gas configurations in the right kidney, which fit with the diagnosis of emphysematous pyelonephritis. Two days later, the patient complained of severe pain of the left eye with photophobia and blurred vision. The diagnosis of endogenous endophthalmitis was made. Treatment consisted of vitrectomy of the left eye, silicone oil injection and intravitreal and systemic antibiotics. The pyelonephritis was treated with antibiotics and percutaneous drainage. CONCLUSION: Both endogenous endophthalmitis and emphysematous pyelonephritis are rare complications of infection, which can result in severe damage to the eye and kidney. Treatment comprises both local and systemic therapy. With the increasing number of diabetics, we can expect more rare complications.

Robot-assisted laparoscopic prostatectomy: nodal dissection results during the first 440 cases by two surgeons.

BACKGROUND: Although many studies address the learning curve for robot-assisted laparoscopic prostatectomy (RALP), little is known concerning the results for pelvic lymph node dissection (LND) during RALP. PATIENTS AND METHODS: Between 2006 and 2011, two surgeons performed 904 RALP procedures. LND was performed in 440 (48.6%) cases based on the European Association of Urology guidelines. Both surgeons had extensive experience with open LND for both prostate and bladder cancer. Clinical data were prospectively recorded into an online database. Complications were reported using the Clavien-Dindo system and documented prospectively. RESULTS: For both surgeons, the operative time for LND decreased over time during the first 150 LND procedures. After that, a mean plateau of operative time of 49 minutes for LND was reached. Nodal yield increased from a mean of 10 nodes for the first 50 cases to 14 for cases 351 to 400. The percentage of positive nodes increased significantly in these intervals from 4% to 23.1% (P<0.001, Mann Whitney U test). Overall complications by grade were not significantly different between RALP with or without LND. In 440 LND cases, 5 (1.5%) grade IIIb complications occurred. All were infection related with bowel perforation in one. Symptomatic lymphoceles necessitating drainage were present in five (1.5%) men. Thromboembolic events (0% vs 1.5%) and anastomosis dehiscence (0.2% vs 1.1%) were more common in men with LND. During the learning curve, the incidence of Clavien grade I and II but not grade III and IV complications decreased. CONCLUSION: An improvement pattern for LND during RALP is observed for operative time, nodal yield node positivity rate, and complication rate during the first 400 cases of LND.

Catheter-assisted 18F-FDG-PET/CT imaging of primary bladder cancer: a prospective study.

OBJECTIVE: The purpose of this study was to prospectively investigate the value of a standardized 18F-fluorodeoxyglucose (18F-FDG)-PET/computed tomography (CT) protocol for imaging of primary bladder cancer, using standardized bladder flushing and filling. METHODS: We included 19 patients with cT1-4 bladder cancer. A Foley catheter was inserted before 18F-FDG injection. PET/CT imaging was performed according to four bladder protocols: (1) bladder empty; (2) bladder empty after flushing; (3) bladder filled with 50 ml saline; and (4) bladder filled with 100 ml saline. Tumour visibility was assessed and compared with histopathology or CT and cystoscopy. RESULTS: The procedure was successfully completed in 16 out of 19 patients. The reference standard revealed a bladder tumour in 16 out of 19 patients. Sensitivity of protocols 1 and 2 was 0.38 [95% confidence interval (CI), 0.16-0.64] compared with 0.63 (95% CI, 0.36-0.84) for protocols 3 and 4. CONCLUSION: Flushing and subsequent retrograde filling of the bladder results in the highest rate of tumour visualization and quantification. Flushing alone is inferior.

Extended nodal dissection reduces sexual function recovery after robot-assisted laparoscopic prostatectomy.

BACKGROUND AND PURPOSE: Considering the anatomic proximity of the internal iliac lymph nodes and the pelvic plexus, it may be expected that more extensive pelvic nodal dissection is associated with an increased risk of damage to the small pelvis neural and vascular structures. We evaluate whether nodal dissection is associated with functional outcome after robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: In a series of 798 RARP procedures, 325 (40.7%) patients underwent a lymph node dissection. Continence, sexual function, and lower urinary tract symptoms (LUTS) were assessed using the International Consultation of Incontinence Questionnaire short form (ICIQ)-SF), International Index of Erectile Function-15, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-PR25 questionnaires before and at 6 months intervals after RARP. RESULTS: Preoperative ICIQ-SF, IIEF-15, and PR25-LUTS scores were similar for men with and without nodal dissection. Normal postoperative erectile function (IIEF-EF >24) at 6 months was reported by 1.7%, 9.1%, and 50.4% of men with no, unilateral, and bilateral nerve preservation and normal preoperative erectile function. All domains of the IIEF-15 score showed a negative correlation with the number of removed lymph nodes. In 70 of 325 (21%) cases with nodal dissection, more than 10 nodes were removed. Men with more than 10 nodes removed had lower IIEF-15 domain scores compared with men with 1 to 10 removed lymph nodes. The postoperative ICIQ-SF and PR25-LUTS scores were not associated with extent of nodal dissection. Nodal metastases were found in 5.9% and 15.7% of men with ≤ 10 nodes and >10 nodes removed (P=0.005). In a multivariate analysis, extent of fascia preservation (FP-score), preoperative IIEF-EF, and number of removed nodes were the strongest independent predictors of postoperative erectile function recovery. CONCLUSION: More extensive nodal dissection was associated with impaired postoperative sexual function recovery but not continence and voiding function after RARP, independent of preoperative function and nerve preservation.