Monogenic features of urolithiasis: A comprehensive review.

Objective: Urolithiasis formation has been attributed to environmental and dietary factors. However, evidence is accumulating that genetic background can contribute to urolithiasis formation. Advancements in the identification of monogenic causes using high-throughput sequencing technologies have shown that urolithiasis has a strong heritable component. Methods: This review describes monogenic factors implicated in a genetic predisposition to urolithiasis. Peer-reviewed journals were evaluated by a PubMed search until July 2023 to summarize disorders associated with monogenic traits, and discuss clinical implications of identification of patients genetically susceptible to urolithiasis formation. Results: Given that more than 80% of urolithiases cases are associated with calcium accumulation, studies have focused mainly on monogenetic contributors to hypercalciuric urolithiases, leading to the identification of receptors, channels, and transporters involved in the regulation of calcium renal tubular reabsorption. Nevertheless, available candidate genes and linkage methods have a low resolution for evaluation of the effects of genetic components versus those of environmental, dietary, and hormonal factors, and genotypes remain undetermined in the majority of urolithiasis formers. Conclusion: The pathophysiology underlying urolithiasis formation is complex and multifactorial, but evidence strongly suggests the existence of numerous monogenic causes of urolithiasis in humans.

Application of novel burst wave lithotripsy and ultrasonic propulsion technology for the treatment of ureteral calculi in a bottlenose dolphin (Tursiops truncatus) and renal calculi in a harbor seal (Phoca vitulina).

Marine mammals may develop kidney stones, which can be challenging to treat. We describe burst wave lithotripsy (BWL) and ultrasonic propulsion to treat ureteral calculi in a 48-year-old female bottlenose dolphin (Tursiops truncatus) and to reduce renal stone burden in a 23-year-old male harbor seal (Phoca vitulina). BWL and ultrasonic propulsion were delivered transcutaneously in sinusoidal ultrasound bursts to fragment and reposition stones. Targeting and monitoring were performed with real-time imaging integrated within the BWL system. Four dolphin stones were obtained and fragmented ex vivo. The dolphin case received a 10-min and a 20-min BWL treatment conducted approximately 24 h apart to treat two 8-10 mm partially obstructing right mid-ureteral stones, using oral sedation alone. For the harbor seal, while under general anesthesia, retrograde ureteroscopy attempts were unsuccessful because of ureteral tortuosity, and a 30-min BWL treatment was targeted on one 10-mm right kidney stone cluster. All 4 stones fragmented completely to < 2-mm fragments in < 20 min ex vivo. In the dolphin case, the ureteral stones appeared to fragment, spread apart, and move with ultrasonic propulsion. On post-treatment day 1, the ureteral calculi fragments shifted caudally reaching the ureteral orifice on day 9. On day 10, the calculi fragments passed, and the hydroureter resolved. In the harbor seal, the stone cluster was observed to fragment and was not visible on the post-operative computed tomography scan. The seal had gross hematuria and a day of behavior indicating stone passage but overall, an uneventful recovery. BWL and ultrasonic propulsion successfully relieved ureteral stone obstruction in a geriatric dolphin and reduced renal stone burden in a geriatric harbor seal.

Development and external validation of a machine learning-based model to classify uric acid stones in patients with kidney stones of Hounsfield units < 800.

The correct diagnosis of uric acid (UA) stones has important clinical implications since patients with a high risk of perioperative morbidity may be spared surgical intervention and be offered alkalization therapy. We developed and validated a machine learning (ML)-based model to identify stones on computed tomography (CT) images and simultaneously classify UA stones from non-UA stones. An international, multicenter study was performed on 202 patients who received percutaneous nephrolithotomy for kidney stones with HU < 800. Data from 156 (77.2%) patients were used for model development, while data from 46 (22.8%) patients from a multinational institution were used for external validation. A total of 21,074 kidney and stone contour-annotated CT images were trained with the ResNet-18 Mask R-convolutional neural network algorithm. Finally, this model was concatenated with demographic and clinical data as a fully connected layer for stone classification. Our model was 100% sensitive in detecting kidney stones in each patient, and the delineation of kidney and stone contours was precise within clinically acceptable ranges. The development model provided an accuracy of 99.9%, with 100.0% sensitivity and 98.9% specificity, in distinguishing UA from non-UA stones. On external validation, the model performed with an accuracy of 97.1%, with 89.4% sensitivity and 98.6% specificity. SHAP plots revealed stone density, diabetes mellitus, and urinary pH as the most important features for classification. Our ML-based model accurately identified and delineated kidney stones and classified UA stones from non-UA stones with the highest predictive accuracy reported to date. Our model can be reliably used to select candidates for an earlier-directed alkalization therapy.

Innovations in Endourologic Stone Surgery: Contemporary Practice Patterns from a Global Survey.

Objective: The purpose of this study is to evaluate the current availability of technology for urolithiasis treatment and ureteroscopy (URS). Perioperative practice patterns, availability of ureteroscopic technologies, pre- and poststenting practices, and methods to alleviate stent-related symptoms (SRS) were assessed via a survey of members of the Endourological Society. Methods: We distributed a 43-question survey online via the Qualtrics platform to members of the Endourological Society. The survey consisted of questions pertaining to the following topics: general (6), equipment (17), preoperative URS (9), intraoperative URS (2), and postoperative URS (9). Results: A total of 191 urologists responded to the survey and 126 completed all questions of the survey (66%). Fifty-one percent (65/127) of urologists were fellowship trained and dedicated an average of 58% of their practice to stone management. In terms of procedures, most urologists performed URS most commonly (68%), followed by percutaneous nephrolithotomy (23%) and extracorporeal shockwave lithotripsy (11%). Ninety percent (120/133) of respondent urologists purchased a new ureteroscope within the last 5 years (16% single-use scopes, 53% reusable, and 31% purchased both). Fifty-three percent (70/132) of the respondents stated that they would be interested in a ureteroscope that can sense intrarenal pressure, with an additional 28% (37/132) stating they would be interested depending on the cost. Seventy-four percent (98/133) of responders purchased a new laser within the last 5 years, and 59% (57/97) changed their lasering technique due to the new laser. Urologists are performing primary ureteroscopy for obstructing stones in 70% of cases, and prefer prestenting patients for subsequent URS in 30% (on average after 21 days). Seventy-one percent (90/126) of responders insert a ureteral stent after uncomplicated URS, which is removed, on average, after 8 days in uncomplicated cases and 21 days after complicated URS. Most urologists give analgesics, alpha-blockers, and anticholinergics for SRS and <10% prescribe opioids. Conclusion: Our survey revealed urologists' eagerness for the early adoption of novel technologies and adherence to conservative practice patterns focused on patient safety.

The Fate of Residual Fragments After Percutaneous Nephrolithotomy: Results from the Endourologic Disease Group for Excellence Research Consortium.

Background: Residual fragments (RFs) after percutaneous nephrolithotomy (PCNL) have a significant impact on patients' quality of life and clinical course. There is a paucity of studies that evaluate the natural history of RFs after PCNL. The objective of this study is to compare rates of reintervention, complications, stone growth, and passage in patients with RFs >4, ≤4, and ≤2 mm after PCNL. Methods: Sites from the Endourologic Disease Group for Excellence (EDGE) research consortium examined data of PCNL patients from 2015 to 2019 with at least 1-year follow-up. RF passage, regrowth, reintervention, and complications were recorded and RFs were stratified into >4 and ≤4 mm groups, as well as >2 and ≤2 mm groups. Potential predictors for stone-related events after PCNL were determined using multivariable logistic regression analysis. It was hypothesized that larger RF thresholds would result in lower passage rates, faster regrowth, and greater clinically significant events (complications and reinterventions) than smaller RF thresholds. Results: A total of 439 patients with RFs >1 mm on CT postoperative day 1 were included in this study. For RFs >4 mm, rates of reintervention were found to be significantly higher and Kaplan-Meier curve analysis showed significantly higher rates of stone-related events. Passage and RF regrowth were not found to be significantly different compared with RFs ≤4 mm. However, RFs ≤2 mm had significantly higher rates of passage, and significantly lower rates of fragment regrowth (>1 mm), complications, and reintervention compared with RFs >2 mm. On multivariable analysis, older age, body mass index, and RF size were found to be predictive of stone-related events. Conclusions: With the largest cohort to date, this study by the EDGE research consortium further confirms that clinically insignificant residual fragment is problematic for patients after PCNL, particularly in older more obese patients with larger RFs. Our study underscores the importance of complete stone clearance post-PCNL and challenges the use of Clinically insignificant residual fragment (CIFR).

Preoperative patient optimization for endourological procedures: the current best clinical practice.

PURPOSE OF REVIEW: Despite technological advancements in endourological surgery, there is room for improvement in preoperative patient optimization strategies. This review updates recent best clinical practices that can be implemented for optimal surgical outcomes. RECENT FINDINGS: Outcome and complication predictions using novel scoring systems and techniques have shown to assist clinical decision-making and patient counseling. Innovative preoperative simulation and localization methods for percutaneous nephrolithotomy have been evaluated to minimize puncture-associated adverse events. Novel antibiotic prophylaxis strategies and further recognition of risk factors that attribute to postoperative infections have shown the potential to minimize perioperative morbidity. Accumulating data on the roles of preoperative stenting and selective oral alpha-blockers adds evidence to the current paradigm of preventive measures for ureteral injury. SUMMARY: Ample tools and technologies exist that can be utilized preoperatively to improve surgical outcomes. The combination of these innovations, along with validation in larger-scale studies, presents the cornerstone of future urolithiasis management.

Prospective randomized trial of 2 versus 12-weeks of postoperative antibiotics after percutaneous nephrolithotomy in complex patients with infection-related kidney stones.

PURPOSE: Treatment of struvite kidney stones requires complete surgical stone removal combined with antibiotic therapy to eliminate urinary tract infections and preventive measures to reduce stone recurrence. The optimal duration of antibiotic therapy is unknown. We sought to determine if 2- or 12-weeks of antibiotics post percutaneous nephrolithotomy (PNL) for infection stones resulted in better outcomes for stone recurrence and positive urine cultures. MATERIAL AND METHODS: This multi-center, prospective randomized trial evaluated patients with the clinical diagnosis of infection stones. Patients were randomized to 2- or 12-weeks of postoperative oral antibiotics (nitrofurantoin or culture-specific antibiotic) and included if residual fragments were ≤4 mm on computed tomography imaging after PNL. Imaging and urine analyses were performed at 3-, 6-, and 12-months post-procedure. RESULTS: Thirty-eight patients were enrolled and randomized to either 2-weeks (n = 20) or 12-weeks (n = 18) of antibiotic therapy post-PNL. Eleven patients were excluded due to residual fragments >4 mm, and 3 patients were lost to follow-up. The primary outcome was the stone-free rate (SFR) at 6 months post-PNL. At 3-, 6-, and 12-months follow-up, SFRs were 72.7% versus 80.0%, 70.0% versus 57.1%, 80.0% versus 57.1% (p = ns), between 2- and 12-week-groups, respectively. At 3-, 6-, and 12-months follow-up, positive urine cultures were 50.0% versus 37.5%, 50.0% versus 83.3%, and 37.5% versus 100% between 2- and 12-week groups, respectively (p = ns). CONCLUSIONS: For patients with stone removal following PNL, neither 2-weeks nor 12-weeks of postoperative oral antibiotics is superior to prevent stones and recurrent positive urine cultures.

Quality of Life of Urolithiasis Patients During the COVID-19 Pandemic: A Multi-Institutional Cross-Sectional Study.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic is an unprecedented global event that has caused significant fear and anxiety across all populations. To date, there have been no studies on how major health crises have affected the stone-related quality of life (QOL) of urolithiasis patients. In this multi-institutional study, we investigated the association between fear of COVID-19 and the QOL of urolithiasis patients during the COVID-19 pandemic using the Fear of COVID-19 Scale (FCV-19S) and the Wisconsin Stone Quality of Life (WISQOL) questionnaires. Materials and Methods: Patient-reported data collection occurred between April and October 2020 during the COVID-19 pandemic where many procedures (radiologic or surgical) and visits were either delayed or cancelled. The scores generated from patient-reported responses to questionnaires were correlated and then further subanalyzed dependent on categorical responses related to procedural delays or care and were analyzed via the Student's t-test. A single factor analysis of variance (ANOVA) was performed to analyze varying QOL scores across the FCV-19S quartiles. Results: Four hundred respondents participated in this study. Overall mean total standardized FCV-19S and WISQOL scores (both transformed to min-max 0-100) were 34.3 and 70.3, respectively. A significant inverse correlation (r = -0.265, p < 0.0001) demonstrated that suggesting greater COVID-19 fear may result in lower stone-related QOL. A significant difference in fear and QOL scores was observed between the sexes, with women having more COVID-19 fear (35.8 vs 28.6, p < 0.01) and lower stone-related QOL (64.2 vs 75.2, p < 0.01). Quartile ANOVA analysis revealed significant mean difference in WISQOL scores across all FCV-19S score quartiles (p < 0.05). Conclusions: Using two validated questionnaires (FCV-19S and WISQOL) and correlating patient-reported responses, we found that greater fear for COVID-19 was associated with lower stone-related QOL in urolithiasis patients.

Evaluation of a Single-Use Flexible Cystoscope: A Multi-Institutional International Study.

Introduction: Acquisition costs and prohibitively expensive technical support for endoscope maintenance, repair, and reprocessing have deterred adoption of flexible cystoscopes by many urologists internationally. This study evaluated the performance of a novel single-use digital cystoscope that can directly connect to a laptop or computer monitor for visualization, obviating the need for a tower. Materials and Methods: The performance characteristics of flexible single-use cystoscopes (NeoScope) were prospectively evaluated vs a reusable flexible cystoscope (Olympus) in three clinical cases and two independent benchtop testing episodes in Canada. Cystoscope maneuverability, imaging, deflection, irrigation, and ease of use of instrumentation were investigated. Additional investigations were performed during clinical use in Zimbabwe (7 patients), Egypt (10 patients), and Dominica (5 patients). Results: Bench testing revealed smaller tip diameter (4.06 vs 6.09 mm) and shorter (35.4 vs 38 cm) single-use cystoscopes vs reusable cystoscopes. Deflection of the single-use scope was superior with an empty working channel (230 up/220 down) vs the reusable (195 up/95 down) but showed a more substantial decrease in deflection on placement of instruments including a grasper. Clinical use revealed satisfactory maneuverability, ease of use of instruments, deflection, and visualization. Conclusions: Benchtop testing performance of the single-use digital flexible cystoscopes was inferior compared with reusable digital cystoscopes. However, these single-use endoscopes offer adequate illumination, imaging, and maneuverability. Direct connection to any computer monitor allowed truly portable use, allowing for treatment of patients in a variety of clinical settings without the need for ancillary equipment.

Ureteral stents: the good the bad and the ugly.

PURPOSE OF REVIEW: Ureteral stents are necessary in the routine practice of an urologist. Choosing the correct stent and being aware of the options available will allow urologists to provide the best possible care for patients and value to the healthcare system. This review seeks to educate urologists regarding improvements in stent technology currently available or in development. RECENT FINDINGS: Research from around the world is underway to discover an ideal stent - one that is comfortable for patients, resists infection and encrustation and is affordable for hospital systems. Stent design alterations and stent coatings are revealing reductions in encrustation and bacterial colonization. Biodegradable stents and magnetic stents are being tested to prevent the discomfort of cystoscopic removal. Intraureteral stents are proving efficacious while eliminating an irritating coil from the bladder and the symptoms associated with it. SUMMARY: The studies highlighted in this review provide encouraging results in the pursuit of the ideal stent while opening discussion around new concepts and further areas of research.

Wheezing in children with pertussis associated with delayed pertussis diagnosis.

BACKGROUND: The classic clinical features of paroxysmal pertussis are often absent in older children and adults and after vaccination. The California pertussis epidemic of 2010 occurred in a highly vaccinated population. METHODS: All pediatric patients (0-18 years) with positive pertussis polymerase chain reaction from July to December 2010 were identified retrospectively from the Kaiser SCAL database. Information extracted by chart review included age at diagnosis, vaccine history, race, cough duration, number of clinic visits before diagnosis, presence of paroxysms, post-tussive emesis or wheezing, treatment for asthma during the course of illness and exposure to confirmed or suspected pertussis cases. RESULTS: Overall 501 pediatric patients (mean age = 8.4 years) with positive pertussis nasopharyngeal polymerase chain reaction were identified. Complete DTaP series and Tdap vaccine had been received by 93% and 38% of eligible patients, respectively. Paroxysms, post-tussive emesis and wheezing on physical examination were present in 34%, 30% and 8% of patients, respectively. Each was associated with a longer duration of symptoms at diagnosis. Wheezing was associated with a delay in diagnosis (60% requiring >1 clinic visit for diagnosis vs. 29% in the overall population, P < 0.0001). Documented exposures were associated with a more timely pertussis diagnosis (after 9.4 days vs. 14.5 days; P < 0.0001). CONCLUSIONS: Wheezing is present on examination of some patients with pertussis in a highly vaccinated pediatric population and appears to delay the diagnosis of pertussis. The presence of wheezing should not be used to exclude this diagnosis in children with chronic cough or other reasons to suspect pertussis.

Factors associated with patient absenteeism for scheduled endoscopy.

AIM: To identify risk factors to help predict which patients are likely to fail to appear for an endoscopic procedure. METHODS: This was a retrospective, chart review, cohort study in a Canadian, tertiary care, academic, hospital-based endoscopy clinic. Patients included were: those undergoing esophagogastroduodenoscopy, colonoscopy or flexible sigmoidoscopy and patients who failed to appear were compared to a control group. The main outcome measure was a multivariate analysis of factors associated with truancy from scheduled endoscopic procedures. Factors analyzed included gender, age, waiting time, type of procedure, referring physician, distance to hospital, first or subsequent endoscopic procedure or encounter with gastroenterologist, and urgency of the procedure. RESULTS: Two hundred and thirty-four patients did not show up for their scheduled appointment. Compared to a control group, factors statistically significantly associated with truancy in the multivariate analysis were: non-urgent vs urgent procedure (OR 1.62, 95% CI 1.06, 2.450), referred by a specialist vs a family doctor (OR 2.76, 95% CI 1.31, 5.52) and office-based consult prior to endoscopy vs consult and endoscopic procedure during the same appointment (OR 2.24, 95% CI 1.33, 3.78). CONCLUSION: Identifying patients who are not scheduled for same-day consult and endoscopy, those referred by a specialist, and those with non-urgent referrals may help reduce patient truancy.

The cytotoxic effect of anthrax lethal toxin on human lung cells in vitro and the protective action of bovine antibodies to PA and LF.

The excretion of protein toxins by vegetative cells of Bacillus anthracis is critical to the development of the lethal consequences of anthrax, particularly inhalational anthrax. Whilst the lung macrophages and other phagocytic cells transfer the spores from the lung cavities into the lymphatic system, and provide an initial germination site for the proliferation of the vegetative cells, it appears that much of the tissue pathology at the time of the host's death could be due to the action of the toxins, especially lethal toxin-protective antigen (PA) plus lethal factor (LF). The widespread tissue oedema and hypoxia may in part reflect a direct attack by lethal toxin on vascular endothelial cells. Also the distribution of the receptor for PA on a variety of cell types including epithelial cells as well as endothelial cells, and the involvement of the lungs in the pathology raises the question of whether lung epithelial cells are also susceptible to lethal toxin. To investigate this possibility a series of in vitro cytotoxicity experiments were carried out with human lung epithelial cells and microvascular endothelial cells. In these experiments lethal toxin (PA 500 ng ml(-1) plus 10-100 ng ml(-1) LF) was shown to cause a progressive loss of cell viability that developed slowly over at least 3 days. Affinity purified bovine colostrum antibodies for both PA and LF were equally effective in providing a 100% protection for epithelial cells from this cytotoxic action of lethal toxin. This was achieved at a 10:1 molar ratio of the particular antibody to its respective target.

Acute sensorineural hearing loss associated with peginterferon and ribavirin combination therapy during hepatitis C treatment: outcome after resumption of therapy.

Peginterferon and ribavirin combination therapy for the treatment of hepatitis C virus (HCV) is well known to be associated with significant adverse effects. Sensorineural hearing loss, that in most cases is unilateral, has been reported as a consequence of therapy with both non-pegylated and pegylated interferon (pegIFN) but is not a well-known adverse effect. We report a 45-year-old Caucasian woman who developed acute sensorineural hearing loss 2 mo after starting therapy with pegIFN-alpha 2b and ribavirin for the treatment of chronic HCV, genotype 1a. She did not report the hearing loss to the hepatitis clinic until 1 mo, later whereupon therapy was promptly discontinued. Although her serum alanine aminotransferase (ALT) normalized and her HCV-RNA became undetectable after 12 wk of pegIFN and ribavirin therapy, after discontinuation, her HCV-RNA became detectable with significant elevations of serum ALT. Four months after initial discontinuation, the patient re-commenced pegIFN and ribavirin combination therapy. After 44 of 48 wk of therapy, the patient's liver biochemistry has normalized and the HCV-RNA is undetectable. She has not developed worsening of her hearing loss and hearing on the left-side is unaffected. Both patients and physicians should be aware that sensorineural hearing loss may occur with pegIFN therapy. Our experience suggests that re-institution of therapy is not always associated with further hearing impairment.

Treatment of chronic hepatitis C in Canadian prison inmates.

PURPOSE: To assess sustained viral response rate and adherence to standard interferon alpha-2b and ribavirin therapy in inmates with chronic hepatitis C (HCV) in Canadian penitentiaries in the Pacific region. METHODS: A retrospective chart review of all inmates with chronic HCV who were treated with standard interferon alpha-2b and ribavirin therapy between March 2001 and October 2002. RESULTS: A total of 90 male inmates were treated. The mean age at time of treatment was 40 years. There were 49 inmates with HCV genotype 1, 11 with HCV genotype 2 and 30 with HCV genotype 3. Eight inmates discontinued treatment because of intolerance to side effects. Nine inmates were stopped by the physician because of nonresponse at an average of 27 weeks. All inmates achieved at least 80% adherence of interferon and ribavirin therapy. The overall sustained virological response (SVR) was 55.9%. SVR was 31.6% for genotype 1, 100% for genotype 2 and 71.4% for genotype 3. CONCLUSION: There was excellent SVR and adherence to treatment with interferon and ribavirin. This experience highlights an important opportunity to treat a population with a high prevalence of HCV-positive persons who may otherwise not seek treatment.

Outsourced teleradiology imaging services: an analysis of discordant interpretation in 124,870 cases.

PURPOSE: Outsourcing after-hours radiology coverage to a teleradiology coverage company has become common in recent years. However, concerns have been raised over the quality of these types of coverage and the implications on patient care. This study details the quality assurance program of a teleradiology company that provides after-hours coverage to 64 California hospitals. METHOD: The records of all examinations interpreted by 10 radiologists during 2003 were reviewed. Interpretations were compared with the final interpretations of the host practices and evaluated for timeliness. RESULTS: A total of 124,870 radiologic studies were interpreted by 10 teleradiologists during 2003. Computed tomography (CT) comprised 74% of these examinations: CT head (35%) examinations were the most commonly transmitted examinations, and CT abdomen/pelvis examinations were the second most common studies (27%). The average turnaround time was 12.2 min; 93% of the examinations were reported within 30 min, and 99% were completed within 1 hour. The overall discordant rate for individual teleradiologists ranged from 0.70% to 1.41%, with an average of 1.09%. Of the most commonly ordered examinations, CT of the abdomen/pelvis had the highest rate of discordance, at 2.1%. CONCLUSIONS: Outsourcing to a teleradiology program with an active quality-assurance program can be safe. An active quality-assurance program should be an integral component of any teleradiology program. Constant feedback improves the performance of the radiologists.

Advanced colon cancer before the age of 20 years: a case for extension of the current colonoscopy surveillance guidelines in hereditary nonpolyposis colorectal cancer syndrome.

BACKGROUND: Hereditary nonpolyposis colorectal cancer (HNPCC) currently accounts for between 2% to 6% of all colorectal adenocarcinomas. Controversies exist regarding the current guidelines for colonoscopic screening for colon cancer. CASE REPORT: A case of colon cancer in a young Japanese man with a family history of colon cancer that did not meet the criteria for HNPCC is reported. A malignant pelvic mass discovered shortly before his 20th birthday prompted a colonoscopy. The findings at colonoscopy determined that the patient and his family fulfilled the criteria of HNPCC. CONCLUSION: Before finding a pelvic mass metastatic from adenocarcinoma of the ascending colon, this patient was clearly outside of the current guidelines for HNPCC screening. It is suggested that in similar patients, even if they do not fulfill all the criteria for HNPCC, it would be appropriate to consider screening well before the recommended lower age.

Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants.

OBJECTIVE: To evaluate the safety and immunogenicity of two lots of a heptavalent Streptococcus pneumoniae conjugate vaccine (PCV) containing seven capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to the outer membrane complex of Neisseria meningitidis serogroup B (OMPC) and administered to infants at 2, 4, 6, and 12 months of age. METHODS: One hundred twenty infants were randomly assigned to concurrently receive PCV-OMPC and one of two Haemophilus influenzae type b (Hib) conjugate-DTwP combination vaccines: (1) Hib with a heterologous protein carrier (CRM(197), TETRAMUNE, Group 1) or (2) an experimental Hib-hepatitis b combination vaccine with the homologous carrier (OMPC, Group 2). All infants in Groups 1 and 2 received PCV-OMPC (lot 1) at 12 months of age. Another separate group of 120 infants (Group 3) received a different lot of PCV-OMPC concurrently with Hib-CRM(197) (TETRAMUNE) at 2, 4, and 6 months of age and then were randomized to receive either PCV-OMPC or a 23-valent polysaccharide (PS) pneumococcal vaccine at 12 months of age. RESULTS: Each PCV-OMPC lot was generally well tolerated and no vaccine-related serious adverse events were reported. Following the primary series, serotype-specific anti-pneumococcal geometric mean concentrations (GMC) were highest for serotypes 14, 19F, and 4 and lowest for serotypes 6B and 23F. GMC and seroconversion rates in Group 3 (lot 2) were lower than in Group 1 (lot 1) for serotypes 6B, 14, 18C, and 23F. Antibody responses to serotypes 6B, 14, and 18C were significantly lower in Group 2 compared to Group 1. Following a booster dose of PCV-OMPC at 12 months of age, each lot was immunogenic with at least a 5-10-fold increase in antibody levels, and responses were significantly higher among those who received the PS vaccine. CONCLUSIONS: PCV-OMPC is generally safe in infants, displays variable immune response by serotype, and concomitant receipt of Hib vaccine with homologous carrier may impact on its immunogenicity.