Mucosal boosting enhances vaccine protection against SARS-CoV-2 in macaques.

A limitation of current SARS-CoV-2 vaccines is that they provide minimal protection against infection with current Omicron subvariants1,2, although they still provide protection against severe disease. Enhanced mucosal immunity may be required to block infection and onward transmission. Intranasal administration of current vaccines has proven inconsistent3-7, suggesting that alternative immunization strategies may be required. Here we show that intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 challenge. A total of 40 previously immunized rhesus macaques were boosted with a bivalent Ad26 vaccine by the intramuscular, intranasal and intratracheal routes, or with a bivalent mRNA vaccine by the intranasal route. Ad26 boosting by the intratracheal route led to a substantial expansion of mucosal neutralizing antibodies, IgG and IgA binding antibodies, and CD8+ and CD4+ T cell responses, which exceeded those induced by Ad26 boosting by the intramuscular and intranasal routes. Intratracheal Ad26 boosting also led to robust upregulation of cytokine, natural killer, and T and B cell pathways in the lungs. After challenge with a high dose of SARS-CoV-2 BQ.1.1, intratracheal Ad26 boosting provided near-complete protection, whereas the other boosting strategies proved less effective. Protective efficacy correlated best with mucosal humoral and cellular immune responses. These data demonstrate that these immunization strategies induce robust mucosal immunity, suggesting the feasibility of developing vaccines that block respiratory viral infections.

Bayesian pooling versus sequential integration of small preclinical trials: a comparison within linear and nonlinear modeling frameworks.

Bayesian sequential integration is an appealing approach in drug development, as it allows to recursively update posterior distributions as soon as new data become available, thus considerably reducing the computation time. However, preclinical trials are often characterized by small sample sizes, which may affect the estimation process during the first integration steps, particularly when complex PK-PD models are used. In this case, sequential integration would not be practicable, and trials should be pooled together. This work is aimed at comparing simple Bayesian pooling with sequential integration through a simulation study. The two techniques are compared under several scenarios using linear as well as nonlinear models. The results of our simulation study encourage the use of Bayesian sequential integration with linear models. However, in the case of nonlinear models several caveats arise. This paper outlines some important recommendations and precautions in that respect.

Bayesian sequential integration within a preclinical pharmacokinetic and pharmacodynamic modeling framework: Lessons learned.

The present manuscript aims to discuss the implications of sequential knowledge integration of small preclinical trials in a Bayesian pharmacokinetic and pharmacodynamic (PK-PD) framework. While, at first sight, a Bayesian PK-PD framework seems to be a natural framework to allow for sequential knowledge integration, the scope of this paper is to highlight some often-overlooked challenges while at the same time providing some guidances in the many and overwhelming choices that need to be made. Challenges as well as opportunities will be discussed that are related to the impact of (1) the prior specification, (2) the choice of random effects, (3) the type of sequential integration method. In addition, it will be shown how the success of a sequential integration strategy is highly dependent on a carefully chosen experimental design when small trials are analyzed.

Development of a replication-deficient adenoviral vector-based vaccine candidate for the interception of HPV16- and HPV18-induced infections and disease.

High-risk Human papilloma virus (HPV) types are the causative agents of cervical cancer and several other anogenital malignancies. The viral proteins expressed in the (pre)malignant cells are considered ideal targets for immunological intervention. Many approaches have been evaluated for this purpose, mostly aiming at the induction of HPV16 E7- and/or E6-specific cellular immunogenicity. As clinical success has so far been limited, novel approaches are required. We describe the development and pre-clinical testing of a vaccine candidate consisting of replication-deficient adenovirus type 26 and 35 based vectors for the interception of HPV16- and HPV18-related disease. We developed HPV16- and HPV18-specific antigens consisting of fusion proteins of E2, E6 and E7. The vaccine will be suitable for every disease stage, from incident and persistent infections where E2 is predominantly expressed up to late stages where E6 and E7 expression are upregulated. Importantly E6 and E7 are present as reordered fragments to abrogate the transforming activity of these two proteins. Loss of transforming activity was demonstrated in different in vitro models. Robust T-cell immunogenicity was induced upon immunization of mice with the vaccine candidate. Finally, the developed vaccine vectors showed considerable therapeutic efficacy in the TC-1 mouse model. The absence of transforming activity of the antigens and the favorable immunogenicity profile of the adenovirus based vectors along with the fact that these vectors can be readily produced on a large scale makes this approach attractive for clinical evaluation.

Differential effects of proteins and carbohydrates on postprandial blood pressure-related responses.

Diet composition may affect blood pressure (BP), but the mechanisms are unclear. The aim of the present study was to compare postprandial BP-related responses to the ingestion of pea protein, milk protein and egg-white protein. In addition, postprandial BP-related responses to the ingestion of maltodextrin were compared with those to the ingestion of sucrose and a protein mix. We hypothesised that lower postprandial total peripheral resistance (TPR) and BP levels would be accompanied by higher plasma concentrations of nitric oxide, insulin, glucagon-like peptide 1 (GLP-1) and glucagon. On separate occasions, six meals were tested in a randomised order in forty-eight overweight or obese adults with untreated elevated BP. Postprandial responses of TPR, BP and plasma concentrations of insulin, glucagon, GLP-1 and nitrite, nitroso compounds (RXNO) and S-nitrosothiols (NO(x)) were measured for 4 h. No differences were observed in TPR responses. Postprandial BP levels were higher after the ingestion of the egg-white-protein meal than after that of meals containing the other two proteins (P≤ 0·01). The ingestion of the pea-protein meal induced the highest NO(x) response (P≤ 0·006). Insulin and glucagon concentrations were lowest after the ingestion of the egg-white-protein meal (P≤ 0·009). Postprandial BP levels were lower after the ingestion of the maltodextrin meal than after that of the protein mix and sucrose meals (P≤ 0·004), while postprandial insulin concentrations were higher after the ingestion of the maltodextrin meal than after that of the sucrose and protein mix meals after 1-2 h (P≤ 0·0001). Postprandial NO(x), GLP-1 and glucagon concentrations were lower after the ingestion of the maltodextrin meal than after that of the protein mix meal (P≤ 0·008). In conclusion, different protein and carbohydrate sources induce different postprandial BP-related responses, which may be important for BP management. Lower postprandial BP levels are not necessarily accompanied by higher NO(x), insulin, glucagon or GLP-1 responses.

Peak transgene expression after intramuscular immunization of mice with adenovirus 26-based vector vaccines correlates with transgene-specific adaptive immune responses.

Non-replicating adenovirus-based vectors have been broadly used for the development of prophylactic vaccines in humans and are licensed for COVID-19 and Ebola virus disease prevention. Adenovirus-based vectored vaccines encode for one or more disease specific transgenes with the aim to induce protective immunity against the target disease. The magnitude and duration of transgene expression of adenovirus 5- based vectors (human type C) in the host are key factors influencing antigen presentation and adaptive immune responses. Here we characterize the magnitude, duration, and organ biodistribution of transgene expression after single intramuscular administration of adenovirus 26-based vector vaccines in mice and evaluate the differences with adenovirus 5-based vector vaccine to understand if this is universally applicable across serotypes. We demonstrate a correlation between peak transgene expression early after adenovirus 26-based vaccination and transgene-specific cellular and humoral immune responses for a model antigen and SARS-CoV-2 spike protein, independent of innate immune activation. Notably, the memory immune response was similar in mice immunized with adenovirus 26-based vaccine and adenovirus 5-based vaccine, despite the latter inducing a higher peak of transgene expression early after immunization and a longer duration of transgene expression. Together these results provide further insights into the mode of action of adenovirus 26-based vector vaccines.

The Biodistribution of the Spike Protein after Ad26.COV2.S Vaccination Is Unlikely to Play a Role in Vaccine-Induced Immune Thrombotic Thrombocytopenia.

Ad26.COV2.S vaccination can lead to vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare but severe adverse effect, characterized by thrombocytopenia and thrombosis. The mechanism of VITT induction is unclear and likely multifactorial, potentially including the activation of platelets and endothelial cells mediated by the vaccine-encoded spike protein (S protein). Here, we investigated the biodistribution of the S protein after Ad26.COV2.S dosing in three animal models and in human serum samples. The S protein was transiently present in draining lymph nodes of rabbits after Ad26.COV2.S dosing. The S protein was detected in the serum in all species from 1 day to 21 days after vaccination with Ad26.COV2.S, but it was not detected in platelets, the endothelium lining the blood vessels, or other organs. The S protein S1 and S2 subunits were detected at different ratios and magnitudes after Ad26.COV2.S or COVID-19 mRNA vaccine immunization. However, the S1/S2 ratio did not depend on the Ad26 platform, but on mutation of the furin cleavage site, suggesting that the S1/S2 ratio is not VITT related. Overall, our data suggest that the S-protein biodistribution and kinetics after Ad26.COV2.S dosing are likely not main contributors to the development of VITT, but other S-protein-specific parameters require further investigation.

Blood pressure decreases more after high-carbohydrate meals than after high-protein meals in overweight adults with elevated blood pressure, but there is no difference after 4 weeks of consuming a carbohydrate-rich or protein-rich diet.

The replacement of dietary carbohydrates with proteins can lower blood pressure (BP), but the mechanisms remain unclear. This randomized, double-blind, parallel-group study aimed to compare 12-h postprandial sympathetic and hemodynamic responses after high-protein (HP) meals and high-carbohydrate (HC) meals. Fifty-two men and women with untreated elevated BP were tested on d 1 and after 4 wk of supplementation [3 × 20 g protein (HP) or maltodextrin (HC) per day]. No between-group differences were found in postprandial plasma norepinephrine on d 1 and at wk 4. On d 1, postprandial mean arterial pressure (MAP) decreased more in the HC group than in the HP group (P = 0.002). This difference was not present at 4 wk, because the postprandial decline in MAP tended to become larger in the HP group after 4 wk of supplementation (P = 0.07). On both test days, postprandial total peripheral resistance tended to decrease more in the HC group (P < 0.08). After 4 wk of supplementation, cardiac output tended to increase more in the HC group (P = 0.08). In conclusion, ingestion of an HP diet induced a smaller decrease in BP on d 1 than did ingestion of an HC diet. This difference disappeared after 4 wk due to a more pronounced decrease in BP in the HP group after 4 wk than on d 1. These findings cannot explain the BP-lowering effect ascribed to dietary proteins.

Right-ventricular enlargement in arrhythmogenic right-ventricular cardiomyopathy is associated with decreased QRS amplitudes and T-wave negativity.

BACKGROUND: Arrhythmogenic right-ventricular cardiomyopathy (ARVC) can lead to RV dilatation. We hypothesized that electrocardiographic characteristics including QRS amplitudes in the extremity- and precordial leads, the S amplitude in lead V1 , and extent of T-wave negativity over the precordial leads are related to RV dilatation in this condition. METHODS: In 42 ARVC patients and 42 controls, we correlated total QRS amplitude in the extremity leads (∑QRSext ), precordial leads (∑QRSprec ) and in all leads (∑QRStot : summation of ∑QRSext and ∑QRSprec ), S amplitude in lead V1 and the extent of T-wave inversion in the precordial leads (V1 vs. beyond V1 ) with RV end diastolic diameter (RVEDD) by echocardiography. RESULTS: In the ARVC group, the mean age was 46 ± 14 years, 31 patients were male, 28 had an implantable cardioverter defibrillator (ICD), and 7 had a LV ejection fraction (EF) < 55%. The control group was age- and gender matched to the ARVC cohort. In contrast to controls, the ∑QRSext (regression coefficient (RC), -0.29; P = 0.020), ∑QRSprec (RC, -0.20; P = 0.015), and ∑QRStot (RC, -0.14; P = 0.009) were lower with RV dilatation in ARVC. S amplitude in lead V1 was not related to RV diameter (RC, -0.98; P = 0.088). Precordial T-wave inversion beyond lead V1 (V2 -V6 ) was associated with a larger RV diameter (RC, 8.58; P = 0.012). CONCLUSIONS: Summed QRS amplitudes in the extremity and precordial leads, and T-wave inversion beyond lead V1 are associated with RV dilatation in patients with ARVC.

Ischemia Index to predict post coronary artery bypass graft change in left ventricular ejection fraction.

INTRODUCTION: Both myocardial necrosis and ischemia can decrease the left ventricular ejection fraction (LVEF). An accurate estimate of the relative contributions of these irreversible and potentially reversible factors could lead to better decisions regarding the risk and benefit of coronary artery bypass grafting (CABG). The value of an Ischemia Index calculated by subtracting the ECG estimated infarction dependent LVEF from the measured LVEF to predict post-operative improvement of LVEF was studied in 55 patients with LVEF <40% before CABG. Patients were grouped according to absence or presence of other coexisting ECG confounders. RESULTS: No significant (p=0.083) relationship was found between the Ischemia Index and the improvement in LVEF after CABG in the overall population, but a strong trend was present in the patients with ECGs without confounding QRS changes (p=0.056). CONCLUSION: These results suggest a positive relationship between the Ischemia Index and improvement of LVEF after CABG in patients without electrocardiographic confounders, but a prospective study using a larger sample is needed.

Intravenous Administration of Ad26.COV2.S Does Not Induce Thrombocytopenia or Thrombotic Events or Affect SARS-CoV-2 Spike Protein Bioavailability in Blood Compared with Intramuscular Vaccination in Rabbits.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a very rare but serious adverse reaction that can occur after Ad26.COV2.S vaccination in humans, leading to thrombosis at unusual anatomic sites. One hypothesis is that accidental intravenous (IV) administration of Ad26.COV2.S or drainage of the vaccine from the muscle into the circulatory system may result in interaction of the vaccine with blood factors associated with platelet activation, leading to VITT. Here, we demonstrate that, similar to intramuscular (IM) administration of Ad26.COV2.S in rabbits, IV dosing was well tolerated, with no significant differences between dosing routes for the assessed hematologic, coagulation time, innate immune, or clinical chemistry parameters and no histopathologic indication of thrombotic events. For both routes, all other non-adverse findings observed were consistent with a normal vaccine response and comparable to those observed for unrelated or other Ad26-based control vaccines. However, Ad26.COV2.S induced significantly higher levels of C-reactive protein on day 1 after IM vaccination compared with an Ad26-based control vaccine encoding a different transgene, suggesting an inflammatory effect of the vaccine-encoded spike protein. Although based on a limited number of animals, these data indicate that an accidental IV injection of Ad26.COV2.S may not represent an increased risk for VITT.

Combination Ad26.RSV.preF/preF protein vaccine induces superior protective immunity compared with individual vaccine components in preclinical models.

Respiratory syncytial virus (RSV) is a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously shown that a prefusion (preF) conformation-stabilized RSV F protein antigen and an adenoviral vector encoding RSV preF protein (Ad26.RSV.preF) are immunogenic and protective in animals when administered as single components. Here, we evaluated a combination of the 2 components, administered as a single injection. Strong induction of both humoral and cellular responses was shown in RSV-naïve and pre-exposed mice and pre-exposed African green monkeys (AGMs). Both components of the combination vaccine contributed to humoral immune responses, while the Ad26.RSV.preF component was the main contributor to cellular immune responses in both mice and AGMs. Immunization with the combination elicited superior protection against RSV A2 challenge in cotton rats. These results demonstrate the advantage of a combination vaccine and support further clinical development.

Avulsion of puborectalis muscle and other risk factors for cystocele recurrence: a 2-year follow-up study.

INTRODUCTION AND HYPOTHESIS: This study aimed to determine the relationship of recurrent cystocele with avulsion of puborectalis muscle and other risk factors. METHODS: In this prospective observational cohort study, 245 women undergoing anterior colporrhaphy were invited for a 2-year follow-up visit consisting of a questionnaire, physical examination, and translabial 3D ultrasonography. Women with and without recurrent cystocele were compared to identify recurrence risk factors. RESULTS: Of the 245 women, 156 agreed to the follow-up visit (63.7%). Objective recurrence rate was 80 of 156 (51.3%). Seventeen of the 156 (10.9%) reported subjective recurrence. Risk factors for anatomical recurrence were complete avulsion of puborectalis muscle (OR, 2.4; 95% CI, 1.3, 4.7), advanced preoperative stage (OR, 2.0; 95% CI, 1.0, 4.1), family history of prolapse (OR, 2.4; 95% CI, 1.2, 4.9), and sacrospinous fixation (OR, 6.5; 95% CI, 2.0, 21.2). CONCLUSIONS: Risk factors for anatomical cystocele recurrence after anterior colporrhaphy were complete avulsion of puborectalis muscle, advanced preoperative stage, family history of prolapse, and sacrospinous fixation.

Sequential use of Ad26-based vaccine regimens in NHP to induce immunity against different disease targets.

The adenovirus (Ad)26 serotype-based vector vaccine Ad26.COV2.S has been used in millions of subjects for the prevention of COVID-19, but potentially elicits persistent anti-vector immunity. We investigated if vaccine-elicited immunity to Ad26 vector-based vaccines significantly influences antigen-specific immune responses induced by a subsequent vaccination with Ad26 vector-based vaccine regimens against different disease targets in non-human primates. A homologous Ad26 vector-based vaccination regimen or heterologous regimens (Ad26/Ad35 or Ad26/Modified Vaccinia Ankara [MVA]) induced target pathogen-specific immunity in animals, but also persistent neutralizing antibodies and T-cell responses against the vectors. However, subsequent vaccination (interval, 26-57 weeks) with homologous and heterologous Ad26 vector-based vaccine regimens encoding different target pathogen immunogens did not reveal consistent differences in humoral or cellular immune responses against the target pathogen, as compared to responses in naïve animals. These results support the sequential use of Ad26 vector-based vaccine regimens targeting different diseases.

Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models.

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.

Protection against Marburg Virus and Sudan Virus in NHP by an Adenovector-Based Trivalent Vaccine Regimen Is Correlated to Humoral Immune Response Levels.

The Marburg virus (MARV) and Sudan virus (SUDV) belong to the filovirus family. The sporadic human outbreaks occur mostly in Africa and are characterized by an aggressive disease course with high mortality. The first case of Marburg virus disease in Guinea in 2021, together with the increased frequency of outbreaks of Ebola virus (EBOV), which is also a filovirus, accelerated the interest in potential prophylactic vaccine solutions against multiple filoviruses. We previously tested a two-dose heterologous vaccine regimen (Ad26.Filo, MVA-BN-Filo) in non-human primates (NHP) and showed a fully protective immune response against both SUDV and MARV in addition to the already-reported protective effect against EBOV. The vaccine-induced glycoprotein (GP)-binding antibody levels appear to be good predictors of the NHP challenge outcome as indicated by the correlation between antibody levels and survival outcome as well as the high discriminatory capacity of the logistic model. Moreover, the elicited GP-specific binding antibody response against EBOV, SUDV, and MARV remains stable for more than 1 year. Overall, the NHP data indicate that the Ad26.Filo, MVA-BN-Filo regimen may be a good candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks.

Is the screening method of sacral neuromodulation a prognostic factor for long-term success?

PURPOSE: We evaluated whether there is a difference in long-term outcomes between patients screened with percutaneous nerve evaluation and a first stage tined lead procedure. We also evaluated the outcome in patients who only responded to screening with the tined lead procedure after failed initial percutaneous nerve evaluation. MATERIALS AND METHODS: We evaluated all patients screened for eligibility to receive sacral neuromodulation treatment since the introduction of the tined lead technique in our center in 2002. In May 2009 all implanted patients were asked to maintain a voiding diary to record the effect of sacral neuromodulation on urinary symptoms. Chi-square analysis was used to evaluate differences in the long-term outcomes of the separate screening methods. RESULTS: A total of 92 patients were screened for sacral neuromodulation. Of the 76 patients screened with percutaneous nerve evaluation 35 (46%) met the criteria for permanent implantation. In 11 of the 16 patients (69%) who underwent direct screening with the tined lead procedure permanent stimulators were placed. Of the 41 patients in whom percutaneous nerve evaluation failed and who subsequently underwent screening with tined lead procedure 18 (44%) were implanted with a neurostimulator after a successful response. Statistical analysis showed no difference between screening type and long-term success (p = 0.94). CONCLUSIONS: The first stage tined lead procedure is a more sensitive screening tool than percutaneous nerve evaluation but long-term success seems to be independent of the screening method. Patients in whom percutaneous nerve evaluation initially failed but who responded to prolonged screening the with tined lead procedure appeared to be as successful as those who directly responded to percutaneous nerve evaluation or the tined lead procedure.

The use of bilateral sacral nerve stimulation in patients with loss of unilateral treatment efficacy.

PURPOSE: We evaluated whether bilateral sacral nerve stimulation can be effective to restore treatment efficacy in patients in whom unilateral sacral neuromodulation fails. MATERIALS AND METHODS: Patients in whom unilateral sacral neuromodulation failed were included in analysis. The percutaneous nerve evaluation test was used to evaluate the effect of contralateral and bilateral stimulation. The stimulation electrode was placed in the contralateral S3 foramen and symptoms were self-recorded using a 3-day voiding diary. Clinical success was defined as more than 50% improvement in at least 1 relevant voiding diary parameter vs baseline. RESULTS: The 15 study patients underwent test stimulation with percutaneous nerve evaluation. In 3 patients lead migration was suspected and, thus, they were not included in analysis. Four of the remaining 12 patients had a successful response to percutaneous nerve evaluation, of whom 3 were eventually implanted with a contralateral lead. After 12 months of treatment 2 of the 3 patients had a successful outcome. CONCLUSIONS: In this pilot study only a select group of patients appeared to benefit from bilateral stimulation after unilateral therapy failure. Further investigation is needed to determine the predictive factors and cost-effectiveness of this treatment.

Advanced maternal age, short interpregnancy interval, and perinatal outcome.

OBJECTIVE: The purpose of this study was to evaluate whether the association between short interpregnancy intervals and perinatal outcome varies with maternal age. STUDY DESIGN: We performed a retrospective cohort study among 263,142 Dutch women with second deliveries that occurred between 2000 and 2007. Outcome variables were preterm delivery (<37 weeks of gestation), low birthweight in term deliveries (<2500 g) and small-for-gestational age (<10th percentile for gestational age on the basis of sex- and parity-specific Dutch standards). RESULTS: Short interpregnancy intervals (<6 months) was associated positively with preterm delivery and low birthweight, but not with being small for gestational age. The association of short interpregnancy interval with the risk of preterm delivery was weaker among older than younger women. There was no clear interaction between short interpregnancy interval and maternal age in relation to low birthweight or small for gestational age. CONCLUSION: The results of this study indicate that the association of short interpregnancy interval with preterm delivery attenuates with increasing maternal age.

Postoperative catheterization after anterior colporrhaphy: 2 versus 5 days. A multicentre randomized controlled trial.

INTRODUCTION AND HYPOTHESIS: The aim of this study was to compare the number of temporary catheter replacements and urinary tract infections after indwelling catheterization for 2 versus 5 days following an anterior colporrhaphy. METHODS: Two hundred forty-six patients were randomly assigned to 2 or 5 days of indwelling catheterization. Outcome measures were temporary catheter replacements because of post-voiding residual >200 mL after removal of the indwelling catheter, urinary tract infections, and hospital stay. All patients were analyzed according to the intention to treat principle. RESULTS: Compared to the 5-day protocol group, in the 2-day protocol group more patients needed temporary catheter replacement (9% versus 28%, odds ratio (OR) 4.0, confidence interval (CI) 1.9-8.3, p < 0.01), whereas less patients had a urinary tract infection (37% versus 22%, OR 0.5, CI 0.3-0.9, p = 0.02) and median hospital stay was lower. CONCLUSIONS: Removal of an indwelling catheter after 2 versus 5 days following anterior colporrhaphy is associated with more temporary catheter replacements, but less urinary tract infections and a shorter hospital stay.