The Electrophysiology Laboratory: Anesthetic Considerations and Staffing Models.

The electrophysiology laboratory facilitates complex procedures on patients, many of whom have advanced disease processes and extensive comorbidities. Historically, nurses administered sedation as required, but in recent years a shift to anesthesiologist-led sedation has been promoted for patient safety and advanced therapeutic considerations. Uncertainty remains, however, regarding whether the electrophysiology laboratory is best staffed with general or cardiothoracic anesthesiologists. In this article, the authors discuss the anesthetic considerations of some commonly performed electrophysiology and structural cardiac procedures and the pros and cons of staffing with general or cardiothoracic anesthesiologists.

Endocrine emergencies in anesthesia.

PURPOSE OF REVIEW: An increasing number of patients with endocrine disorders will present to the operating rooms. In this review, we outline the common endocrine disorders that the anesthesiologist may face in the perioperative time span, review the controversies in optimal management, as well as summarize the recent literature for the management of these complex patients. RECENT FINDINGS: Perioperative management of pheochromocytoma and paraganglioma has been facilitated by improved medical management and the adoption of minimally invasive surgical techniques. An improved understanding of the sequelae of carcinoid syndrome has resulted in safer perioperative management. Perioperative glycemic management requires a fundamental understanding of perioperative fluid resuscitation and adverse events associated with the new generation oral hyperglycemic agents to prevent avoidable complications. SUMMARY: Endocrine disorders will commonly present in the perioperative time period and the anesthesiologist plays a critical role in achieving good operative outcomes.

Prevalence of Thyroid Autoimmunity in Women with Recurrent Pregnancy Loss.

Background and objectives: Thyroid autoimmunity (TAI) has been associated with a significantly increased risk of miscarriage in women with recurrent pregnancy loss (RPL). The aim of this study was to determine the prevalence of TAI in women with RPL and compare the clinical characteristics of positive and negative TAI women. Materials and Methods: This is a retrospective cross-sectional study; 203 women with RPL were included. Thyroid profile, anti-thyroid peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies were measured in all participants. Clinical characteristics and causes of RPL were compared between positive and negative TAI. Results: Prevalence of TAI was 14.8%; prevalence of positive TPO-Ab and TG-Ab was 12.3% and 4.9%, respectively. Women with TAI had significantly higher concentrations of thyrotropin (TSH) compared to women without TAI (4.8 ± 3.8 versus 3.1 ± 1.1, p = 0.001). There was no significant difference in age, the number of gestations, miscarriages, state of antiphospholipid antibodies (aPL), or causes of RPL between women that were TAI-positive versus TAI-negative. Prevalence of positive TAI by cause of RPL was: endocrine 7/25 (28%), genetic 1/5 (20%), autoimmune 1/5 (20%), anatomic 8/55 (14.5%), and unexplained cause 13/112 (11.6%). Conclusions: The prevalence of TAI in women with RPL is 14.8%. Women with an endocrine cause have the highest prevalence of TAI.

Modified Anesthesia Protocol for Electroconvulsive Therapy Permits Reduction in Aerosol-Generating Bag-Mask Ventilation during the COVID-19 Pandemic.

INTRODUCTION: Electroconvulsive therapy (ECT) is a critical procedure in psychiatric treatment, but as typically delivered involves the use of bag-mask ventilation (BMV), which during the COVID-19 pandemic exposes patients and treatment staff to potentially infectious aerosols. OBJECTIVE: To demonstrate the utility of a modified anesthesia protocol for ECT utilizing preoxygenation by facemask and withholding the use of BMV for only those patients who desaturate during the apneic period. METHODS: This chart review study analyzes patients who were treated with ECT using both the traditional and modified anesthesia protocols. RESULTS: A total of 106 patients were analyzed, of whom 51 (48.1%) required BMV using the new protocol. Of clinical factors, only patient BMI was significantly associated with the requirement for BMV. Mean seizure duration reduced from 52.0 ± 22.4 to 46.6 ± 17.1 s, but seizure duration was adequate in all cases. No acute physical, respiratory, or psychiatric complications occurred during treatment. CONCLUSIONS: A modified anesthesia protocol reduces the use of BMV by more than 50%, while retaining adequate seizure duration.

Perioperative ß-blocker use: what is new in 2020?

PURPOSE OF REVIEW: Although the indications for ß-blockers in the management of patients with congestive heart failure and myocardial infarction are well established, the use of ß-blockers in the perioperative setting remains controversial. RECENT FINDINGS: Since 2008 PeriOperative ISchemic Evaluation Trial, there have been numerous studies suggesting that perioperative ß-blockers are associated with adverse events such as hypotension, bradycardia, increased mortality, and stroke. SUMMARY: In this article, we review the most recent evidence to suggest an approach to perioperative ß-blocker use tailored to patient and surgical risk factors. We also review recent studies on off-label uses for perioperative ß-blockers.

Nonoperating room anesthesia in different parts of the world.

PURPOSE OF REVIEW: Advances in early diagnosis and treatment of diseases using minimally invasive procedures has led to an increase in the number of cases in locations outside the operating room. This surge created the need for anesthesia services to expand to these areas to provide well tolerated and favorable procedural conditions. The present review describes nonoperating room anesthesia patterns in different parts of the world. RECENT FINDINGS: Nonoperating room anesthesia has grown exponentially over the last years. Patients scheduled in these areas are sicker and older compared to the operating room patients. Anesthesiologist-directed care has proven to be well tolerated, with less serious complications and improvement in patients and proceduralist satisfaction. SUMMARY: There are marked variations in how anesthesia services are delivered in out of operating room locations in different parts of the world. Although there are some data available from the United States, expansion of minimally invasive procedures across continents will likely lead to the emergence of various models of delivering anesthetic care.

Suplementos nutricionales para prevención de diabetes mellitus gestacional: lecciones aprendidas basadas en la evidencia.

INTRODUCTION: Gestational diabetes mellitus (GDM) affects between 5 and 40% of pregnant women. Recently different interventions with nutritional supplements have been evaluated for prevention of GDM. AIM: To perform a synthesis of the evidence on the efficacy of nutritional supplements (myo-inositol, probiotics, and vitamin D) in the prevention of GDM. METHODS: A systematic search in PubMed and Cochrane library was performed, including systematic reviews of randomized clinical trials (RCTs), published in English or Spanish until May 2020, using the keywords: "prevention", "gestational diabetes", "hyperglycemia and pregnancy", "supplementation", "probiotics", "myo-inositol" and "vitamin D". RESULTS: 10 systematic reviews that met the inclusion criteria were analyzed. Myo-inositol supplementation compared to placebo decreased the incidence of GDM (RR: 0.44 [0.27-0.87]; five RCTs), low quality of evidence. Although the supplementation with vitamin D or probiotics during pregnancy could reduce the incidence of GDM the evidence is limited. CONCLUSIONS: Myo-inositol supplementation is effective for prevention of GDM in high-risk women. Supplementation with vitamin D or probiotics probably decreases the incidence of GDM.

INTRODUCTION: La diabetes mellitus gestacional (DMG) afecta a entre el 5 y el 40% de mujeres embarazadas. Recientemente se han evaluado diferentes intervenciones con suplementos nutricionales para prevenir la DMG. OBJETIVO: Realizar una síntesis de la evidencia sobre eficacia de suplementos nutricionales (mioinositol, probióticos y vitamina D) para prevenir DMG. MÉTODO: Se realizó una búsqueda sistemática en PubMed y la biblioteca Cochrane, se incluyeron revisiones sistemáticas de estudios clínicos aleatorizados (ECAs), publicados en idioma inglés o español hasta mayo de 2020; se utilizaron las palabras clave: "prevención", "diabetes gestacional", "hiperglicemia y embarazo", "suplementación", "probióticos", "mio-inositol" y "vitamina D". RESULTADOS: Se analizaron 10 revisiones sistemáticas que cumplieron los criterios de inclusión. La suplementación con mioinositol comparado con placebo disminuyó la incidencia de DMG (RR: 0.44; IC 95%: 0.27-0.87; cinco ECAs). Si bien la suplementación con vitamina D o probióticos durante el embarazo podría disminuir la incidencia de DMG, la evidencia es limitada. CONCLUSIONES: La suplementación con mioinositol es efectiva para prevenir DMG en mujeres de alto riesgo. La suplementación con vitamina D o probióticos probablemente disminuye la incidencia de DMG.

Uso de mioinositol más Bifidobacterium lactis y Lactobacillus rhamnosus para la prevención de diabetes mellitus gestacional en mujeres mexicanas.

AIM: To compare the incidence of gestational diabetes mellitus (GDM) in women with three or more risk factor to developing GDM supplemented with myo-inositol plus probiotics versus women care without supplementation. METHODS: Retrospective cohort study, group 1, women with supplementation (myo-inositol 2g plus Bifidobacterium lactis and Lactobacillus rhamnosus 5x108 UFC, twice per day, from 12-14 to 28 weeks of gestation; group 2, women with prenatal care without supplementation, matched by age and body mass index (BMI). The primary outcome was the incidence of GDM using the International Association of Diabetes and Pregnancy Study Groups criteria. RESULTS: Group 1 n=48, group 2 n=96. There were no significant baseline differences between groups in age, BMI and number of risk factors. The incidence of GDM in group 1 was n=14 (29.2%), and for group 2 n=46 (47.9%); RR: 0.61 (95% CI: 0.37-0.99; p = 0.03). CONCLUSIONS: Supplementation from 12-14 weeks of gestation with myo-inositol plus probiotics decrease the incidence of GDM in Mexican women.

OBJETIVO: Comparar la incidencia de diabetes mellitus gestacional (DMG) en mujeres con tres o más factores de riesgo para desarrollar DMG suplementadas con mioinositol más probióticos versus mujeres sin suplementación.­. MATERIAL Y ­MÉTODOS: Estudio de cohorte retrospectivo, grupo 1, mujeres con suplementación (mioinositol 2 g más Bifidobacterium lactis y Lactobacillus rhamnosus 5x108unidades formadoras de colonias, dos veces al día, de las 12-14 hasta las 28 semanas de gestación); grupo 2, mujeres con control prenatal habitual sin suplementación, pareadas por edad e índice de masa corporal (IMC). El resultado primario fue la incidencia de DMG utilizando los criterios de la Asociación Internacional de Grupos de Estudio de Diabetes y Embarazo. RESULTADOS: Grupo 1, n = 48, y grupo 2 n = 96. No hubo diferencias significativas en características basales como edad, IMC, y numero de factores de riesgo entre los grupos. La incidencia de DMG en el grupo 1 fue n = 14 (29.2%) y en el grupo 2 n = 46 (47.9%); RR: 0.61 (IC 95%: 0.37-0.99; p = 0.03). CONCLUSIONES: La suplementación desde las 12-14 semanas de gestación con mioinositol más probióticos disminuye la incidencia de DMG en mujeres mexicanas.

Adherence to the Western, Prudent, and Mediterranean dietary patterns and chronic lymphocytic leukemia in the MCC-Spain study.

Diet is a modifiable risk factor for several neoplasms but evidence for chronic lymphocytic leukemia (CLL) is sparse. Previous studies examining the association between single-food items and CLL risk have yielded mixed results, while few studies have been conducted on overall diet, reporting inconclusive findings. This study aimed to evaluate the association between adherence to three dietary patterns and CLL in the multicase-control study (MCC-Spain) study. Anthropometric, sociodemographic, medical and dietary information was collected for 369 CLL cases and 1605 controls. Three validated dietary patterns, Western, Prudent and Mediterranean, were reconstructed in the MCC-Spain data. The association between adherence to each dietary pattern and CLL was assessed, overall and by Rai stage, using mixed logistic regression models adjusted for potential confounders. High adherence to a Western dietary pattern (i.e. high intake of high-fat dairy products, processed meat, refined grains, sweets, caloric drinks, and convenience food) was associated with CLL [ORQ4 vs. Q1=1.63 (95%CI 1.11; 2.39); P-trend=0.02; OR 1-SD increase=1.19 (95%CI: 1.03; 1.37)], independently of Rai stages. No differences in the association were observed according to sex, Body Mass Index, energy intake, tobacco, physical activity, working on a farm, or family history of hematologic malignancies. No associations were observed for Mediterranean and Prudent dietary patterns and CLL. This study provides the first evidence for an association between a Western dietary pattern and CLL, suggesting that a proportion of CLL cases could be prevented by modifying dietary habits. Further research, especially with a prospective design, is warranted to confirm these findings.

[Alternative HPV vaccination schedules in Latin America].

In 2008, the first HPV vaccination program in Latin America started in Panama, targeting girls aged 10-11 years with a 3-dose vaccine schedule, an initiative that was to be followed by other Latin American countries after local feasibility and population acceptability evaluations were completed. A 3-dose vaccine regimen over six months was originally chosen for HPV vaccines, copying the Hepatitis B vaccine schedule (0, 1-2, 6 months). Alternative vaccine schedules have been proposed afterwards based on: i) noninferior immunogenicity or immune response levels compared to those at which clinical efficacy has been proven (i.e., those observed in a 3-dose HPV vaccine schedule in women aged 15-26), and, ii) proven efficacy in clinical trials and/or effectiveness among women who were provided less than three doses due to a lack of adherence to a 3-dose vaccine schedule. In 2014, based on the available evidence and the potential increase in coverage by expansion of vaccination target groups, particularly in low and middle income countries (LMIC), the World Health Organization recommended a 2-dose schedule with at least a 6-month interval between doses for females up to 15 years of age and a 3-dose schedule for older women. More recently, it has been suggested that 1-dose HPV vaccination schemes may provide enough protection against HPV infection and may speed up the introduction of HPV vaccination in LMIC, where most needed.

En 2008, se inició en Panamá el primer programa de vacunación contra el virus del papiloma humano (VPH), dirigido a niñas de 10 a 11 años, utilizando un esquema de tres dosis en seis meses, iniciativa que fue adoptada por otros países de la región tras evaluar la aceptabilidad en la población y la viabilidad de llevar a cabo el programa. Inicialmente, el esquema de tres dosis para las vacunas contra el VPH se basó en el utilizado en la vacunación contra la hepatitis B (0, 1-2, 6 meses). Posteriormente, se han propuesto esquemas de vacunación alternativos, utilizando evidencia sobre: i) la inmunogenicidad o niveles de respuesta inmune no inferiores a aquéllos con los cuales la eficacia clínica de la vacuna fue probada (es decir, aquéllos observados con tres dosis en mujeres de 15 a 26 años); y ii) la eficacia demostrada en ensayos clínicos y efectividad demostrada en mujeres a quienes se vacunó con menos de tres dosis debido a falta de adherencia al esquema completo de tres dosis. En 2014, la Organización Mundial de la Salud recomendó un esquema de dos dosis con al menos seis meses de intervalo entre dosis para mujeres de hasta 15 años de edad y uno de tres dosis para mujeres mayores. La recomendación se basó en la evidencia disponible hasta entonces y a un posible aumento en cobertura mediante la ampliación de los grupos etarios a vacunarse, particularmente en países de ingresos bajos y medios (PIBMs). Más recientemente, se ha sugerido un esquema de vacunación contra el VPH de una sola dosis, el cual podría proporcionar suficiente protección contra la infección por VPH y así acelerar la introducción de la vacunación contra el VPH en PIBMs donde más se necesita.

Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia.

PURPOSE: There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic variability in vitamin C transporter gene SLC23A2 could explain some inconsistencies in the literature. METHODS: Fruit/vegetable/vitamin C consumption from food frequency questionnaires and six low-penetrance genetic susceptibility polymorphisms in vitamin C transporter gene SLC23A2 (rs1715364, rs6133175, rs1776948, rs6139587, rs369270 and rs6052937) were examined in 434 CLL cases and 1257 randomly selected controls from primary care centres with genetic data of whom 275 cases and 1094 controls having both diet and genetic information. Logistic regression models were used to estimate odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: CLL patients were more likely to have a higher fruit consumption than controls (highest versus lowest quartile in g/day OR: 1.48; 95 % CI: 1.00 to 2.18; P = 0.03), whereas no associations were found with vegetable or total vitamin C intake. Based on log-additive models, rs6133175_A > G (OR: 1.19, 95 % CI: 1.00 to 1.41; P = 0.05) and rs1776948_T > A (OR: 1.20; 95 %CI: 1.01 to 1.41; P = 0.04) were associated with CLL. The haplogenotype analysis (rs1715364, rs6133175) supported the genotype results. No gene-diet interactions in CLL remained statistically significant after correction for multiple testing. CONCLUSIONS: These data suggest that both fruit intake and genetic marker in SLC23A2 may play an independent role in CLL biology.

Night shift work and chronic lymphocytic leukemia in the MCC-Spain case-control study.

Chronic lymphocytic leukemia (CLL) has few known modifiable risk factors. Recently, circadian disruption has been proposed as a potential contributor to lymphoid neoplasms' etiology. Serum melatonin levels have been found to be significantly lower in CLL subjects compared with healthy controls, and also, CLL prognosis has been related to alterations in the circadian molecular signaling. We performed the first investigation of an association between night shift work and CLL in 321 incident CLL cases and 1728 population-based controls in five areas of Spain. Participants were interviewed face-to-face by trained interviewers to collect information on sociodemographic factors, familial, medical and occupational history, including work shifts and other lifestyle factors. We used logistic regression models adjusted for potential confounders to estimate odds ratios (OR) and 95% confidence intervals (CI). Seventy-nine cases (25%) and 339 controls (20%) had performed night work. Overall, working in night shifts was not associated with CLL (OR = 1.06; 95% CI = 0.78-1.45, compared with day work). However, long-term night shift (>20 years) was positively associated with CLL (OR(tertile 3 vs . day-work) = 1.77; 95% = 1.14-2.74), although no linear trend was observed (P trend = 0.18). This association was observed among those with rotating (OR(tertile 3 vs . day-work) = 2.29; 95% CI = 1.33-3.92; P trend = 0.07), but not permanent night shifts (OR(tertile 3 vs . day-work) = 1.16; 95% CI = 0.60-2.25; P trend = 0.86). The association between CLL and long-term rotating night shift warrants further investigation.

HPV vaccination impact on a cervical cancer screening program: methods of the FASTER-Tlalpan Study in Mexico.

OBJECTIVE: To outline the design of a clinical trial to evaluate the impact of HPV vaccination as part of a hrHPV-based primary screening program to extend screening intervals. MATERIALS AND METHODS: A total of 18,000 women aged 25-45 years, attending the regular cervical cancer-screening program in primary health care services in Tlalpan, Mexico City, will be invited to the study. Eligible participants will be assigned to one of three comparison groups: 1) HPV16/18 vaccine and hrHPV-based screening; 2) HPV6/11/16/18 vaccine and hrHPV-based screening; 3) Control group who will receive only hrHPV-based screening. Strict surveillance of hrHPV persistent infection and occurrence of precancerous lesions will be conducted to estimate safety profiles at different screening intervals; participants will undergo diagnosis confirmation and treatment as necessary. CONCLUSION: The FASTER-Tlalpan Study will provide insights into new approaches of cervical cancer prevention programs. It will offer valuable information on potential benefits of combining HPV vaccination and hrHPV-based screening to safety extend screening intervals.

Seroreactivity against Merkel cell polyomavirus and other polyomaviruses in chronic lymphocytic leukaemia, the MCC-Spain study.

Merkel cell polyomavirus (MCPyV) has been suspected to cause chronic lymphocytic leukaemia (CLL) but previous data are inconsistent. We measured seroreactivities of nine polyomaviruses (MCPyV, BKPyV, JCPyV, LPyV, KIPyV, WUPyV, HPyV-6, HPyV-7 and TSPyV) in 359 CLL cases and 370 controls using bead-based multiplex serology technology. We additionally tested two herpesviruses (HSV-1 and CMV). Associations between disease and viral seroreactivities were assessed using logistic regression. All human viruses showed high seroprevalences (69-99%) against structural proteins in controls but significantly lower viral seroprevalences in cases (58-94%; OR range = 0.21-0.70, P value < 0.05), except for MCPyV (OR = 0.79, 95% CI = 0.54-1.16). Lower seroreactivity levels were observed among CLL subjects, with significant differences already observed at early stages of disease, unrelated to treatment status. Seroreactivities against polyomavirus related oncoproteins were almost null. Our data suggest no association for MCPyV polyomavirus with CLL development and an unlikely association for other polyomaviruses tested.

Preoperative management of medications for psychiatric disorders.

Perioperative medication management is a complex topic. Physicians working in the perioperative space are frequently called upon to make decisions regarding continuing or stopping certain medications. For patients with psychiatric disorders, the overwhelming recommendation is to continue therapy with heightened awareness of anesthesiologists regarding potential side effects or medication interactions.

Pancreatic beta cell function and insulin resistance profiles in first-degree relatives of patients with prediabetes and type 2 diabetes.

AIMS: To evaluate insulin secretion and insulin resistance profiles in individuals with family history of prediabetes and type 2 diabetes. METHODS: This was a cross-sectional study to evaluate clinical and metabolic profiles between individuals with type 2 diabetes, prediabetes and their relatives. There were 911 subjects divided into five groups: (i) normoglycemic (NG), (ii) type 2 diabetes, (iii) prediabetes, (iv) first-degree relatives of patients with type 2 diabetes (famT2D), and (v) first-degree relatives of patients with prediabetes (famPD); anthropometrical, biochemical and nutritional evaluation, as well as insulin resistance and pancreatic beta cell function measurement was performed by oral glucose tolerance to compare between groups. RESULTS: The most prevalent type 2 diabetes risk factors were dyslipidemia (81%), family history of type 2 diabetes (76%), central obesity (73%), male sex (63%), and sedentary lifestyle (60%), and most of them were progressively associated to prediabetes and type 2 diabetes groups. Insulin sensitivity was lower in famT2D groups in comparison to NG group (p < 0.0001). FamPD and famT2D had a 10% lower pancreatic beta cell function (DI) than the NG group (NG group 2.78 ± 1.0, famPD 2.5 ± 0.85, famT2D 2.4 ± 0.75, p˂0.001). CONCLUSIONS: FamPD and famT2D patients had lower pancreatic beta cell function than NG patients, highlighting that defects in insulin secretion and insulin sensitivity appear long time before the development of hyperglycemia in patients genetically predisposed.

Impact of the COVID-19 pandemic on cervical cancer screening participation, abnormal cytology prevalence and screening interval in Catalonia.

Background: The COVID-19 pandemic led to a national lockdown and the interruption of all cancer preventive services, including cervical cancer screening. We aimed to assess the COVID-19 pandemic impact on opportunistic screening participation, abnormal cytology (ASCUS+) prevalence and screening interval in 2020 and 2021 within the Public Health System of Catalonia, Spain. Methods: Individual data on cytology and HPV testing of women aged 25-65 from 2014 to 2021 were retrieved from the Information System for Primary Care Services (SISAP). Time-series regression models were used to estimate expected screening participation and abnormal cytology prevalence in 2020 and 2021. The impact was determined by comparing observed and expected values (ratios). Additionally, changes in screening interval trends between 2014 and 2021 were assessed by fitting a Piecewise linear regression model. Results: Cervical cancer screening participation decreased by 38.8% and 2.2% in 2020 and 2021, respectively, with the most significant impact on participation (-96.1%) occurring in April 2020. Among older women, participation was lower, and it took longer to recover. Abnormal cytology prevalence was 1.4 times higher than expected in 2020 and 2021, with variations by age (range=1.1-1.5). From June 2020 onwards, the screening interval trend significantly changed from an increase of 0.59 to 3.57 months per year, resulting in a median time of 48 months by December 2021. Conclusions: During the pandemic, fewer women have participated in cervical cancer screening, abnormal cytology prevalence has increased, and the screening interval is more prolonged than before. The potential cervical cancer lifetime risk implications highlight the need for organized HPV-based screening.

Bladder cancer and seroreactivity to BK, JC and Merkel cell polyomaviruses: the Spanish bladder cancer study.

An infectious etiology for bladder cancer has long been suspected. Merkel cell virus (MCV), BKV and JCV polyomaviruses are possible causative agents but data remain scarce. Therefore, we evaluated the seroresponse to these three polyomaviruses in association with bladder cancer risk. 1,135 incident bladder cancer subjects from five Spanish regions and 982 hospital controls matched by sex, age and region were included. 99% of cases were urothelial-cell carcinomas. Antibody response against MCV, BKV and JCV was measured by enzyme immunoassay using Virus-Like-Particles. Our results show a similar seroprevalence in cases and controls: 64/60% for BKV, 83/82% for MCV and 87/83% for JCV. However, among seropositive subjects, higher median seroreactivities were observed in cases compared to controls for BKV (0.84 vs. 0.70, p-value = 0.009) and MCV (1.81 vs. 0.65, p-value < 0.001). Increased bladder cancer risk was observed for BKV (OR = 1.4, 95%CI 1.04-1.8) and for MCV (OR = 1.5, 95%CI 1.2-1.9), when comparing highest to lowest seroreactivity tertiles. The associations of BKV and MCV with bladder cancer were independent of each other and neither smoking status nor disease stage and grade modified them. Furthermore, no association was observed between seroresponse to JCV and bladder cancer. Therefore, we conclude that BKV and MCV polyomavirus infection could be related to an increased bladder cancer risk.