Serum biomarkers related to frailty predict negative outcomes in older adults with hip fracture.

PURPOSE: Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. METHODS: A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. RESULTS: The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. CONCLUSIONS: These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

Children's lead exposure in the U.S.: Application of a national-scale, probabilistic aggregate model with a focus on residential soil and dust lead (Pb) scenarios.

Lead (Pb) exposures from soil and dust ingestion contribute to children's blood lead levels (BLLs) in the United States. The U.S. Environmental Protection Agency (EPA)'s Strategy to Reduce Lead Exposures and Disparities in U.S. Communities and the Federal Action Plan to Reduce Childhood Lead Exposure describe multi-pronged collaborative approaches. These include reducing multi-media lead exposures nationally using analytical tools such as EPA's Stochastic Human Exposure and Dose Simulation model for lead [SHEDS-Pb; formerly known as SHEDS-IEUBK (Integrated Exposure Uptake Biokinetic model)], which was initially developed and applied with a focus on children's drinking water exposures. In this study we applied SHEDS-Pb to determine what residential soil Pb and dust Pb concentrations (individually and their sum) can keep BLLs of potentially exposed young children in the general U.S. population below specified values, considering aggregate exposures from water, soil, dust, food, and air. We considered two age groups (1 to <2 years and 2 to <6 years), two BLL values (5 µg/dL and 3.5 µg/dL), and two population percentiles (95th and 97.5th). Sensitivity analyses were conducted using several alternative model inputs and data sets, yielding 15 scenarios summarized in the paper. Of those scenarios, we focused on ones with the most recent science and available data. Modeled soil Pb concentrations by age group, population percentile and reference BLL scenarios for the focus scenarios ranged from 70 ppm to 220 ppm; and modeled dust Pb concentrations ranged from 110 ppm to 240 ppm. These results are consistent with current soil and dust Pb concentrations in the U.S. general population and are lower than most of the current U.S. Federal standards. Estimated BLLs compared well with measured BLLs from CDC's NHANES 2009-2016 (0-27 % relative error for focus scenarios). This analysis can be used to inform EPA and other federal Pb efforts.

Efficacy of Antiresorptive Treatment in Osteoporotic Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: To investigate concerns surrounding the benefits of antiresorptive drugs in older adults, a systematic review was carried out to evaluate the efficacy of these treatments in the prevention of osteoporotic hip fractures in older adults. DESIGN: a systematic review and meta-analysis of randomized clinical trials. SETTING AND PARTICIPANTS: older adults ≥65 years with osteoporosis, with or without a previous fragility fracture. Studies with cancer-related and corticosteroid-induced osteoporosis, participants <65 years and no reported hip fracture were not included. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus databases were searched. The primary outcome was hip fracture, and subgroup analysis (≥75 years, with different drug types and secondary prevention) and sensitivity analysis was carried out using a GRADE evaluation. Secondary outcomes were any type of fractures, vertebral fracture, bone markers and adverse events. The risk of bias was assessment with the Cochrane risk of bias tool. RESULTS: A total of 12 randomised controlled trials (RCTs) qualified for this meta-analysis, with 36,196 participants. Antiresorptive drugs have a statistically significant effect on the prevention of hip fracture (RR=0.70; 95%CI 0.60 to 0.81), but with a moderate GRADE quality of evidence and a high number needed to treat (NNT) of 186. For other outcomes, there is a statistically significant effect, but with a low to moderate quality of evidence. Antiresorptives showed no reduction in the risk of hip fracture in people ≥75 years. The results for different drug types, secondary prevention and sensitivity analysis are similar to the main analyses and have the same concerns. CONCLUSIONS: Antiresorptive drugs have a statistically significant effect on preventing hip fracture but with a moderate quality (unclear/high risk of bias) and high NNT (186). This small benefit disappears in those ≥75 years, but increases in secondary prevention. More RCTs in very old osteoporotic adults are needed.

Overview of virus and cancer relationships. Position paper.

The role of certain viruses in the etiology of some tumors is today indisputable, but there is a lack, however, of annoverview of the relationship between viruses and cancer with amultidisciplinary approach. For this reason, the Health Sciences Foundation has convened a group of professionals from different areas of knowledge to discuss the relationship between viruses and cancer, and the present document is the result of these deliberations. Although viruses cause only 10-15% of cancers, advances in oncology research are largely due to the work done during the last century on tumor viruses. The clearest cancer-inducing viruses are: HPV, HBV, HCV, EBV and, depending on the geographical area, HHV-8, HTLV-1 and HIV. HPVs, for example, are considered to be the causative agents of cervical carcinomas and, more recently, of a proportion of other cancers. Among the Herpes viruses, the association with the development of neoplasms is well established for EBV and HHV-8. Viruses can also be therapeutic agents in certain neoplasms and, thus, some oncolytic viruses with selective tropism for tumor cells have been approved for clinical use in humans. It is estimated that the prophylaxis or treatment of viral infections could prevent at least 1.5 million cancer deaths per year.

International Exercise Recommendations in Older Adults (ICFSR): Expert Consensus Guidelines.

The human ageing process is universal, ubiquitous and inevitable. Every physiological function is being continuously diminished. There is a range between two distinct phenotypes of ageing, shaped by patterns of living - experiences and behaviours, and in particular by the presence or absence of physical activity (PA) and structured exercise (i.e., a sedentary lifestyle). Ageing and a sedentary lifestyle are associated with declines in muscle function and cardiorespiratory fitness, resulting in an impaired capacity to perform daily activities and maintain independent functioning. However, in the presence of adequate exercise/PA these changes in muscular and aerobic capacity with age are substantially attenuated. Additionally, both structured exercise and overall PA play important roles as preventive strategies for many chronic diseases, including cardiovascular disease, stroke, diabetes, osteoporosis, and obesity; improvement of mobility, mental health, and quality of life; and reduction in mortality, among other benefits. Notably, exercise intervention programmes improve the hallmarks of frailty (low body mass, strength, mobility, PA level, energy) and cognition, thus optimising functional capacity during ageing. In these pathological conditions exercise is used as a therapeutic agent and follows the precepts of identifying the cause of a disease and then using an agent in an evidence-based dose to eliminate or moderate the disease. Prescription of PA/structured exercise should therefore be based on the intended outcome (e.g., primary prevention, improvement in fitness or functional status or disease treatment), and individualised, adjusted and controlled like any other medical treatment. In addition, in line with other therapeutic agents, exercise shows a dose-response effect and can be individualised using different modalities, volumes and/or intensities as appropriate to the health state or medical condition. Importantly, exercise therapy is often directed at several physiological systems simultaneously, rather than targeted to a single outcome as is generally the case with pharmacological approaches to disease management. There are diseases for which exercise is an alternative to pharmacological treatment (such as depression), thus contributing to the goal of deprescribing of potentially inappropriate medications (PIMS). There are other conditions where no effective drug therapy is currently available (such as sarcopenia or dementia), where it may serve a primary role in prevention and treatment. Therefore, this consensus statement provides an evidence-based rationale for using exercise and PA for health promotion and disease prevention and treatment in older adults. Exercise prescription is discussed in terms of the specific modalities and doses that have been studied in randomised controlled trials for their effectiveness in attenuating physiological changes of ageing, disease prevention, and/or improvement of older adults with chronic disease and disability. Recommendations are proposed to bridge gaps in the current literature and to optimise the use of exercise/PA both as a preventative medicine and as a therapeutic agent.

Multicomponent exercise program in older adults with lung cancer during adjuvant/palliative treatment: A secondary analysis of an intervention study.

BACKGROUND: Lung cancer is the second most prevalent common cancer in the world and predominantly affects older adults. This study aimed to examine the impact of an exercise programme in the use of health resources in older adults and to assess their changes in frailty status. DESIGN: This is a secondary analysis of a quasi-experimental study with a non-randomized control group. SETTING: Oncogeriatrics Unit of the Complejo Hospitalario de Navarra, Spain. PARTICIPANTS: Newly diagnosed patients with NSCLC stage I-IV. INTERVENTION: Multicomponent exercise programme that combined resistance, endurance, balance and flexibility exercises. Each session lasted 45-50 minutes, and the exercise protocol was performed twice a week over 10 weeks. MEASUREMENTS: Mortality, readmissions and Visits to the Emergency Department. Change in frailty status according to Fried, VES-13 and G-8 scales. RESULTS: 26 patients completed the 10-weeks intervention (IG). Mean age in the control group (CG) was 74.5 (3.6 SD) vs 79 (3 SD) in the IG, and 78,9% were male in the IG vs 71,4% in the CG. No major adverse events or health-related issues attributable to the testing or training sessions were noted. Significant between-group differences were obtained on visits to the emergency department during the year post-intervention (4 vs 1; p:0.034). No differences were found in mortality rate and readmissions, where an increasing trend was observed in the CG compared with the IG in the latter (2 vs 0; p 0.092). Fried scale was the unique indicator that seemed to be able to detect changes in frailty status after the intervention. CONCLUSIONS: A multicomponent exercise training programme seems to reduce the number of visits to the emergency department at one-year post-intervention in older adults with NSCLC during adjuvant therapy or palliative treatment, and is able to modify the frailty status when measured with the Fried scale.

Performance of the Short Physical Performance Battery in Identifying the Frailty Phenotype and Predicting Geriatric Syndromes in Community-Dwelling Elderly.

The early identification of seniors at high risk of geriatric syndromes is fundamental for targeting interventions to those who most need them. To date, the predictive value of the Short Physical Performance Battery (SPPB) for multifactorial clinical conditions has not been clearly established. Thus, the aim of the present study was to determine whether the SPPB could identify frailty and predict geriatric syndromes in community-dwelling older adults. Participants comprised men and women aged 60 years and older who participated in the Health and Well-being and Aging Survey in Colombia 2015 (n=4125, 57.6% women). A structured interview was administered to obtain socio-demographic data which included age, sex, ethnicity, socioeconomic status, and urbanicity. The study included the measurement of body mass, grip strength, SPPB, Lawton´s instrumental ADL scale, specific subjective memory complaints (SSMC), frailty phenotype (Fried and FRAIL Scale), and self-reported falls, geriatric syndromes and/or medical conditions. ROC analysis was used to examine the ability of the SPPB test to predict frailty and geriatric syndromes. The cutoff that maximized both sensitivity and specificity for the frailty phenotype was 8 points or below for men and 7 points or below for women. These cutoff values significantly predicted four geriatric syndromes in descending order: mild dementia (♂ ORajus 3.34, and ♀ ORajus 2.79), low grip strength (♂ ORajus 1.98, and ♀ ORajus 2.45), falls (♂ ORajus 1.39, and ♀ ORajus 1.49), and SSMC (♂ ORajus 1.39). In summary, the main finding of the present study was that SPPB score (i.e., ≤ 8 ♂ and ≤ 7 ♀) seems to be a useful measure for identifying the physical frailty phenotype and predicting geriatric syndromes in community-dwelling older adults.

Circulating Cytokines and Lower Body Muscle Performance in Older Adults at Hospital Admission.

BACKGROUND: Aging-related traits, including gradual loss of skeletal muscle mass and chronic inflammation, are linked to altered body composition and impaired physical functionality, which are important contributing factors to the disabling process. We sought to explore the potential relationship between lower-body muscle strength decline and inflammatory mediators in older adults. METHODS: We performed a cross-sectional analysis in 38 older adults admitted to an acute care of the elderly unit (57.9% women, mean age=87.9±4.9 years; mean body mass index [BMI]=26.5±4.7 kg/m2). Clinical and functional outcomes including weight, height, BMI, dependence, physical and cognitive performance, and muscle strength measured by one-repetition maximum (1RM) for leg-extension, leg-press, chest-press and handgrip strength, were assessed. Blood serum content of 59 cytokines, chemokines and growth factors was assessed by protein arrays. Multivariate linear regression analyses were used to examine the relationship between cytokine concentrations and muscle strength parameters. RESULTS: After controlling for confounding factors (age, sex, BMI, cumulative illness rating score and physical performance score), 1RM leg-press had a significant negative relationship with GRO (CXCL2) (ß= -18.13, p=0.049), MIG (CXCL9) (ß= -13.94, p=0.004), IGF-1 (ß= -19.63, p=0.003), CK-BETA 8 (CCL23) (ß= -28.31, p=0.018) and GCP-2 (CXCL6) (ß= -25.78, p=0.004). Likewise, 1RM leg-extension had a significant negative relationship with IGFBP-1 (ß= -11.49, p=0.023). CONCLUSIONS: Thus, several serum cytokines/chemokines and growth factors are negatively associated with lower muscle strength in older patients. Further investigation is required to elucidate the mechanism of elevated inflammatory mediators leading to lower muscle strength.

Queratoconjuntivitis por Vittaforma corneae: una enfermedad emergente entre los viajeros que regresan del sudeste asiático / Vittaforma Corneae keratoconjunctivitis: An emerging pathology among travelers returning from Southeast Asia

La queratoconjuntivitis por Microsporidium es un cuadro infrecuente. Se ha asociado a brotes epidémicos en Asia relacionados con la exposición a agua o tierra contaminada. Habitualmente estos cuadros son autolimitados y leves, pero pueden tener evoluciones prolongadas. Presentamos el caso de una paciente de 29 años que comenzó con dolor, enrojecimiento, visión borrosa en su ojo derecho tras su vuelta de un viaje a Singapur y que no mejoró tras un tratamiento convencional frente a conjuntivitis. Fue diagnosticada de queratoconjuntivitis por Microsporidium mediante PCR y tinción con PAS del epitelio corneal. El tratamiento inicial fue desbridamiento epitelial, albendazol oral y voriconazol, levofloxacino y propamidina, pero la enfermedad conjuntival y corneal no cedió hasta que si introdujeron corticoides tópicos 5 meses después para tratar la limbitis. Debemos tener la sospecha de queratitis por Microsporidium en casos de queratitis unilateral y conjuntivitis, sobre todo en pacientes que vuelvan de Asia

Microsporidium keratoconjunctivitis is an very rare disease. It is related to outbreaks in Asia due to exposure to contaminated water or soil. Microsporidium keratoconjunctivitis is a a self-limited disease, but it could have long term courses. We present the case of a 29 year old woman who started with pain, redness and blurred vision after a holiday in Singapore and did not respond to conjunctivitis treatment. PCR sequencing and PAS staining of corneal epithelial biopsy identified Vittaforma corneae as the causative organism. Treatment was initiated with corneal debridement, oral albendazol, and intensive topical voriconazole, levofloxacin and propamidine, but the conjunctival and corneal disease was only resolved 5 months later with the introduction of topical steroids to treat her severe limbitis. Suspicion of Microsporidium keratoconjunctivitis should be raised amongst ophthalmologists in unilateral keratitis with mild conjunctivitis in travelers from Asia

Vittaforma Corneae keratoconjunctivitis: An emerging pathology among travelers returning from Southeast Asia. / Queratoconjuntivitis por Vittaforma corneae: una enfermedad emergente entre los viajeros que regresan del sudeste asiático.

Microsporidium keratoconjunctivitis is an very rare disease. It is related to outbreaks in Asia due to exposure to contaminated water or soil. Microsporidium keratoconjunctivitis is a a self-limited disease, but it could have long term courses. We present the case of a 29 year old woman who started with pain, redness and blurred vision after a holiday in Singapore and did not respond to conjunctivitis treatment. PCR sequencing and PAS staining of corneal epithelial biopsy identified Vittaforma corneae as the causative organism. Treatment was initiated with corneal debridement, oral albendazol, and intensive topical voriconazole, levofloxacin and propamidine, but the conjunctival and corneal disease was only resolved 5 months later with the introduction of topical steroids to treat her severe limbitis. Suspicion of Microsporidium keratoconjunctivitis should be raised amongst ophthalmologists in unilateral keratitis with mild conjunctivitis in travelers from Asia.

Update on the major imported helminth infections in travelers and migrants.

Helminth infections cause considerable morbidity worldwide and may be frequently underdiagnosed especially in areas of lower endemicity. Patients may harbor latent infections that may become symptomatic years or decades after the initial exposure and timely diagnosis may be critical to prevent complications and improve outcomes. In this context, disease in special populations, such as immunosuppressed patients, may be of particular concern. Heightened awareness and recent diagnostic developments may contribute to the correct management of helminth infections in nonendemic regions. A review of the main helminth infections in travelers and migrants (strongyloidiasis, taeniasis-neurocysticercosis and schistosomiasis) is presented, focusing on epidemiology, developments in diagnosis, treatment and prevention.

Evaluation of canine leishmaniosis vaccine CaniLeish® under field conditions in native dog populations from an endemic Mediterranean area-A randomized controlled trial.

Dog vaccination is considered an effective way of reducing Leishmania infantum infection incidence in the canine population, as well as its transmission to humans. However, the use of partially effective vaccines can have the detrimental effect of "masking" vaccinated asymptomatic carriers, capable of harbouring the parasite and transmitting it to naïve individuals. After eight years on the European market, few studies have been released on CaniLeish® vaccine safety and efficacy. The present study, a one-year randomized CaniLeish® vaccine field trial, was performed in a canine leishmaniosis endemic area and included animals selected from a native dog population (n = 168). No severe adverse reactions were observed in vaccinated dogs (n = 85). Cases of active L. infantum infection were detected by serological, molecular and clinical follow-up of dogs. One-year post-vaccination, no differences in number or severity of L. infantum active infections were observed between study groups (n = 4 in each group). Vaccine-induced cellular immunity, assessed through interferon-γ quantification, showed significantly higher levels of this cytokine one-month post-vaccination in the vaccine group (p < 0.001), but no differences were observed after nine months between trial groups (p = 0.078). These results fail to support the reported CaniLeish® efficacy in the prevention of active L. infantum infection in dogs from endemic areas and naturally exposed to the parasite.

Comparison of the toxicity of two treatment schemes with benznidazole for chronic Chagas disease: a prospective cohort study in two Spanish referral centres.

OBJECTIVES: Chagas disease (CD) treatment is limited to two therapeutic options: benznidazole (generally the first option in Spain) and nifurtimox. Both drugs present high rates of adverse reactions and treatment discontinuation and there is no consensus regarding the most effective administration schedule for benznidazole or how to prevent and manage treatment toxicity. We aim to compare the tolerability and treatment discontinuation rate between two different treatment schemes with benznidazole. METHODS: This was a prospective observational study of adult patients with CD, enrolled from January 2014 to March 2018 in two referral centres in Madrid (Spain). Participants were treated either with benznidazole 5 mg/kg/day (full dose) over 60 days (benznidazole standard dose scheme (BSD)), or with an escalating dose lasting 5 days up to a maximum of 300 mg/day (benznidazole increasing dose scheme (BID)). RESULTS: 471 patients were analysed: 201 in the BSD group and 270 in the BID group. There were no significant differences regarding age (40.4 (SD 8.7) vs 41 (SD 8.2) years), sex (74.1% (149/201) vs 68.5% (185/270) women), weight (69.4 (SD 12.8) vs 68.9 (SD 11) kg) or nationality (97.5% (196/201) vs 96.7% (261/270) Bolivians) between groups. There were also no differences in adverse reactions rate (55.2% (111/201) vs 55.6% (150/270)), number of adverse reactions per patient, adverse reactions type (except for arthralgias and myalgias which occurred more frequently in the BID group (0% (0/111) BSD vs 8% (12/150) BID; p 0.002)) and degree and time to first adverse reactions. There was significantly more treatment discontinuation (49.8% (100/201) vs 33.0% (89/270); p <0.001) in the BSD group, but not during the first 30 days of treatment (32.3% (65/201) vs 25.6% (69/270); p 0.08). CONCLUSION: The use of increasing doses of benznidazole for 5 days and a maximum dose of 300 mg, does not significantly improve drug tolerability. However, while the treatment discontinuation rates were similar during the first 30 days of treatment, it may improve the treatment completion rate at 60 days.

The impact of canine leishmaniosis vaccination with Canileish® in Leishmania infantum infection seroprevalence studies.

Effective vaccines against Leishmania parasites are a goal for the scientific community working with both canine and human leishmaniosis. However, possible side effects of vaccination should also be considered and evaluated, preferably before vaccine licensing and marketing. One of these possible effects is the cross-reaction of vaccine-induced antibodies with standard serological tests for detection of Leishmania infantum infection. Longitudinal studies were performed on the type of humoral profile induced by Brazilian marketed canine leishmaniosis vaccines, but little is known regarding the European situation. In this study, an annual follow-up of 85 CaniLeish® vaccinated dogs and 83 non-vaccinated control dogs was performed. Blood samples were taken for all animals at pre-determined time points: before vaccination; immediately before each one of the two following vaccine doses (at 21 days intervals); and then one, four, six, nine and 12 months after finishing the vaccination course. All samples were tested by an in-house ELISA, using a whole promastigote antigen, for the presence of anti-L. infantum antibodies. Humoral response detectable by the used serological diagnostic method was significantly higher in the vaccine group when compared with the control group (p < 0.01) until one-month post-vaccination. Results show that CaniLeish® vaccine-induced antibodies cross-react with a commonly used serological test for diagnosis of L. infantum natural infection. Implications of this interference are discussed, with special emphasis on a possible negative impact on canine leishmaniosis surveillance studies.

Anorectal manometry in children with retentive fecal incontinence: What parameters should we evaluate? / Manometría anorrectal en niños con incontinencia fecal retentiva: ¿Qué parámetros debemos evaluar?

INTRODUCTION: Children with functional constipation frequently present with alterations in rectal compliance and the urge-to-defecate sensation that can be evaluated through anorectal manometry (ARM). In the present study, we evaluated the usefulness of the parameters obtained through ARM in children with retentive fecal incontinence (RFI). MATERIALS AND METHODS: Children with functional constipation, aged 4 to 17years, that underwent ARM were included in the study. RESULTS: Of the 35 children evaluated, 21 presented with functional constipation and 14 had functional constipation and RFI. The children with both constipation and RFI tolerated greater volumes of air insufflation for triggering the urge to defecate and reaching maximum tolerance of pain, compared with the children that did not have RFI. We identified the cutoff point of 135ml of air as the maximum tolerance sensation for distinguishing children with RFI. CONCLUSIONS: Maximum tolerance of pain was the most useful parameter for evaluating RFI in children with functional constipation.