Unit Body Surface Area Research Articles

Predictors of extubation in the operating room after pediatric cardiac surgery: A single-center retrospective study

Background: In this study, we aimed to evaluate the outcomes of our on-table extubation strategy in patients with congenital heart disease. Methods: Between April 2021 and November 2022, a total of 114 pediatric patients (58 males, 56 females; median age: 25.3 months; range, 57.5 to 4.4 months) who were operated for congenital heart diseases were retrospectively analyzed. The patients were evaluated according to the Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STS-EACTS) scoring system. Perioperative patient data were analyzed and correlated with the extubation status. Results: Overall, 56% of the patients were extubated in the operating room. There was an association between fluid balance per unit body surface area, longer cardiopulmonary bypass and cross-clamp times and on-table extubation. Lactate value prior to extubation, STS-EACTS mortality category, estimated mortality, and estimated morbidity were statistically significant with regards to the achievability of extubation. Multivariate analysis revealed lactate value prior to extubation and estimated postoperative length of hospital stay to be significant factors affecting on-table extubation. There was a significant correlation between decreased length of intensive care unit and hospital stay and on-table extubation. Conclusion: The outcomes of our on-table extubation strategy for patients with congenital heart disease reveal the feasibility of this approach. Higher lactate and fluid balance/body surface area levels, longer cross-clamp and cardiopulmonary bypass durations, increased surgical complexity are indicators of a failure to perform on-table extubation. This strategy is also associated with shorter intensive care unit and hospital length of stays as an additional clinical benefit.

Phase I study of anlotinib in pediatric patients with high-risk, recurrent, or refractory sarcomas.

e23538 Background: Anlotinib is an orally available, highly potent, novel multitargeted tyrosine kinase inhibitor, which blocks VEGF signaling by selectively targeting VEGFR-2, -3 as well as FGFR-1, -2, -3, -4 with high affinity. We evaluated the toxicity, and pharmacokinetic profile of anlotinib in children with high-risk, recurrent, or refractory sarcomas. Methods: This was an open-label, single-center, single-arm phase I study, which enrolled pediatric patients with sarcoma. Pediatric patients aged 5-18 years diagnosed with high-risk, recurrent, or refractory sarcomas were enrolled and further categorized into cohort A (＜35 kg) or cohort B (≥ 35kg). Anlotinib was administered orally, once daily, 2-week on off, until disease progression, death, unacceptable toxicity, or withdrawal of consent for any reasons. A fixed anlotinib level of 8 mg was given to cohort A and three dose levels (8mg, 10mg, 12mg) were evaluated using a “3 + 3” design in cohort B. Results: Between December 29, 2020, and September 7, 2022, 34 patients were enrolled to evaluate the safety and 19 (55.9%) were evaluable for efficacy. The median age was 12 (range 5-18) years old. The main subtype eligible was rhabdomyosarcoma (23.5%). Two of fifteen patients in cohort A at a dose level of 8 mg experienced dose-limiting toxicity, including grade 3 hematuria and grade 3 hand-foot syndrome. The grade 3 treatment-related adverse events (AEs) included neutropenia (3 [8.8%]), hand-foot syndrome (2 [5.9%]), headache (1 [2.9%]), hematuria (1 [2.9%]), hypertension (1 [2.9%]), and hyperbilirubinemia (1 [2.9%]). The most common AEs were grade 1 or 2 hypothyroidism (58.8%) and abdominal pain (55.9%). Twelve of 19 (63.2%) patients had a best response of stable disease with seven patients receiving ≥ 6 cycles. Age has no significant effect on the level of body exposure per unit body surface area dose, and patients younger than 12 years old had a faster elimination. Conclusions: Anlotinib in pediatric patients with sarcoma was well tolerated. The RP2D of anlotinib for future studies is 8 mg for patients＜ 35 kg and 12 mg for patients with ≥ 35kg. Clinical trial information: NCT04659733 . [Table: see text]

Machine learning for prediction of delirium in patients with extensive burns after surgery.

Machine learning-based identification of key variables and prediction of postoperative delirium in patients with extensive burns. Five hundred and eighteen patients with extensive burns who underwent surgery were included and randomly divided into a training set, a validation set, and a testing set. Multifactorial logistic regression analysis was used to screen for significant variables. Nine prediction models were constructed in the training and validation sets (80% of dataset). The testing set (20% of dataset) was used to further evaluate the model. The area under the receiver operating curve (AUROC) was used to compare model performance. SHapley Additive exPlanations (SHAP) was used to interpret the best one and to externally validate it in another large tertiary hospital. Seven variables were used in the development of nine prediction models: physical restraint, diabetes, sex, preoperative hemoglobin, acute physiological and chronic health assessment, time in the Burn Intensive Care Unit and total body surface area. Random Forest (RF) outperformed the other eight models in terms of predictive performance (ROC:84.00%) When external validation was performed, RF performed well (accuracy: 77.12%, sensitivity: 67.74% and specificity: 80.46%). The first machine learning-based delirium prediction model for patients with extensive burns was successfully developed and validated. High-risk patients for delirium can be effectively identified and targeted interventions can be made to reduce the incidence of delirium.

Protistan epibionts affect prey selectivity patterns and vulnerability to predation in a cyclopoid copepod

Colonisation of crustacean zooplankton with ciliate epibionts is widespread in freshwater and marine environments. However, the ecology of such association are little studied as yet. The occurrence of ciliate epibionts on copepods and the preference towards this association with different life stages of Mesocyclops were studied from winter to spring. Relative susceptibility of zooplankton species was evaluated by analysing the epibiont colonies and zooids and relate this to the surface area of the host. The maximum epibiont infestation per unit body surface area was recorded on copepodites followed by copepod nauplii rather than other zooplankton species, whereas the rotifer Asplanchna was never affected. Influence of climatic factors such as temperature on the colonisation of epibionts on basibionts was found significant. In winter (November to February) samples, copepods were infested by autotrophic epibionts whereas in late spring and early summer (March–April) heterotrophic protists (peritrichian ciliates) were the sole epibionts on copepods. We conducted experiments in the laboratory on prey selection pattern of predators by direct visual and video-graphic observations of various events (encounter, attack, capture, ingestion, prey escape) during predation by infested and uninfested copepodites and adults of Mesocyclops. Postencounter the attack probability was significantly lower in infested than in uninfested copepods. The present paper reports on substrate preference by epibionts and their impacts in food rich and food scarce environments. Furthermore, major environmental interactions were studied with the reproductive phenology of copepods with respect to epibionts and the cause and effect of long term association of epibionts with copepods need to be addressed.

Effects of Heat-Stress on Oocyte Number and Quality and In Vitro Embryo Production in Holstein Heifers

Background: This study aimed to determine the effects of environmental temperature on the number and quality of oocytes and embryo production rates obtained by performing ovum pick up (OPU). Heat stress leads to long-term, short-term, visible, and invisible effects in dairy cows. Its effects on reproduction are evident in all stages, from oocyte development to birth. Disturbance in ovarian follicle development, follicular dominance deficiency, anoestrus, polyspermia, embryoniclosses, decreased fetal growth, and abortion are some examples of responses to these effects. The aim of the present study was aimed to determine the effects of ambient temperature on oocyte quality and number and embryo production rates.Materials, Methods & Results: The animal material used in this study comprised 10 Holstein heifers. At the beginning of the study, the heifers were 13-15 months old. OPU was performed at different times of the year, and weather conditions were recorded. Grouping according to ambient temperature was done as < 10°C (group 1), 10-25°C (group 2), and > 25°C (group 3). The veterinary ultrasonography device and a set of compatible intravaginal OPU probe, catheter, and aspiration device were used for OPU application. All antral follicles with diameters of 2-8 mm in the ovaries were aspirated. The aspirated follicle fluids were examined under a stereo microscope, and the cumulus-oocyte complexes (COC) were collected and classified according to their structure. A, B, and C-quality oocytes were included in the in vitro embryo production process. After performing 69 OPUs on random days of the cycle, the number of oocytes per OPU was found to be 8.72, 6.32, and 6.85 in groups 1, 2, and 3, respectively (P < 0.05). The number of viable oocytes per OPU was 6.83, 4.64, and 4.65 in groups 1, 2, and 3, respectively (P < 0.05). The statistical difference between the first group and the other groups was significant for cleavage and blastocyst counts (P < 0.05).Discussion: All the negative effects of heat stress on animals resulted from the increased body temperature. Reproductive performance is adversely affected by high temperatures and humidity during periods of high ambient temperatures. Metabolic heat is released, and the heat load increases due to the metabolism of nutrients in cattle. Internal body temperature is regulated via the dissipation of metabolic heat to the environment. The amount of heat dissipated via conduction andconvection depends on the unit body weight, surface area, skin and coat color, difference in temperature gradient of the animal and ambient temperature, and humidity. In the present study, it was determined that the blastocyst development rates of the oocytes obtained in the warm season (>25°C [group 3]) were lower than those of the other groups. It was concluded that this may be because the oocytes developed under chronic heat stress in the animals, and several cycles were required to enhance oocyte quality and developmental potential. Additional studies are needed to investigate the response of oocytes obtained with OPU to heat stress during embryonic developmental stages and to determine the sensitivity and effects of embryonic tissue damage according to developmental stages. Based on the results of the present study, it was concludedthat performing OPU and in vitro embryo production (IVEP) when the ambient temperature is close to the thermoneutral limits may increase the blastocyst development rates. Keywords: blastocyst, heat stress, heifer, in vitro embryo production, oocyte quality, ovum pick-up.

Effects of different doses of glucocorticoids on minimally invasive procedures in pain patients with type 2 diabetes

Objective: To investigate the effects of different doses of glucocorticoids on minimally invasive procedures in patients with type 2 diabetes mellitus (T2DM), and optimize the clinical pathways of minimally invasive procedures. Methods: The clinical data of 284 patients with T2DM who received minially invasive procedures from the Department of Pain Medicine, West China Hospital, Sichuan University from May 2017 to May 2020 were retrospectively reviewed. The patients were divided into two groups according to the main diagnostic types: spine-related group (n=148) and herpes zoster group (n=136). According to the cumulative dose of glucocorticoids (GCs) per unit body surface area during the hospitalization, patients were further divided into three subgroups: low-dose group (GCs<3.5 mg/m2), medium-dose group (3.5 mg/m2 ≤GCs<7 mg/m2), and high-dose group (GCs≥7 mg/m2). The clinical characteristics of the patients in different subgroups of the two diseases groups were compared. The effects of the glucocorticoids on the pain intensity, blood glucose, length of hospital stay (LOS) and total hospitalization cost were compared among the 3 subgroups of the two diseases groups. Results: There were no significant differences in the age, gender, height, weight, visual analog scale (VAS) and fasting blood glucose before procedures between the two groups (all P>0.05). The VAS score of the low-dose group from the spine-related group was 4.5±1.6, which was higher than that of the medium-dose group (3.5±1.3) (P=0.004). VAS score was 4.3±1.3 in the medium-dose group and 4.4±1.6 in the high-dose group from the herpes zoster group, which were higher than that in the low-dose group (3.5±0.9) (P=0.006). In terms of blood glucose, the impact on the fasting blood glucose before and after the procedures in the low-dose group from the spine-related group was less than that in the medium dose group (P=0.013). In the herpes zoster group, the blood glucose of the low-dose group was (11±5) mmol/L, which had less influence on the blood glucose fluctuation during the hospitalization than that in the high-dose group [(15±5) mmol/L] (P<0.05). The LOS and hospitalization cost in the low-dose group from the spine-related group were (9±4) d and (10 583±4 851) yuan, respectively, which were less than those in the medium-dose group [(11±3) d and (15 202±7 418) yuan] and high-dose group [(13±6) d and (18 100±4 138) yuan] (all P<0.05); however, there was no significant difference among different subgroups in the herpes zoster group (all P>0.05). Conclusion: When used in the patients with T2DM undergoing minimally invasive procedures for spine-related diseases, low-dose glucocorticoids can obtain more clinical benefit than high dose, and high dose can lead to raised blood glucose, prolong the LOS, and increase the hospitalization cost.

Comparison of Japanese Encephalitis Force of Infection in Pigs, Poultry and Dogs in Cambodian Villages.

Japanese encephalitis virus (JEV) is the main cause of human viral encephalitis in Asia, with a mortality rate reaching 30%, mostly affecting children. The traditionally described cycle involving wild birds as reservoirs, pigs as amplifying hosts and Culex mosquitoes as vectors is questioned, with increasing evidence of a more complex multi-host system involved in areas where densities of pigs are low, such as in Cambodia. In 2018, we examined pigs, chickens, ducks and dogs from Kandal province, Cambodia, for antibody response against JEV by hemagglutination inhibition and virus neutralization assays. Forces of infection (FOI) for flaviviruses and JEV were estimated per species and per unit of body surface area (BSA). JEV seroprevalence reached 31% (95% CI: 23–41%) in pigs, 1% (95% CI: 0.1–3%) in chickens, 12% (95% CI: 7–19%) in ducks and 35% (95% CI: 28–42%) in dogs. Pigs were most likely to be infected (FOI: 0.09 per month), but the FOI was higher in ducks than in pigs for a given BSA (ratio of 0.13). Dogs had a lower FOI than ducks but a higher FOI than chickens (0.01 per month). For a given BSA, dogs were less likely to be infected than pigs (ratio of 1.9). In Cambodia, the virus may be circulating between multiple hosts. Dogs live in close contact with humans, and estimating their exposure to JEV infection could be a relevant indicator of the risk for humans to get infected, which is poorly known due to underdiagnosis. Understanding the JEV cycle and developing tools to quantify the exposure of humans is essential to adapt and support control measures for this vaccine-preventable disease.

Blood pressure load per body surface area is higher in women than in men.

Many unexplained sex differences have been observed in blood pressure (BP) related morbidity. However, there has been little research about the most obvious difference between men and women-body size. Given that blood vessels are organs of tubular shape, we hypothesized that correction of BP for body surface area (BSA), a two-dimensional measurement of body size, would allow comparison of BP load between men and women. We assessed the relationship of 24-h ambulatory BP measurements and BSA in 534 participants (mean age 61 ± 3 years, 51% women) from the Helsinki Birth Cohort Study. The study subjects had no previous medication affecting vasculature or BP. When BP values were adjusted for age, smoking, physical activity, and body fat percentage, males had higher ambulatory daytime mean systolic BP (131 mmHg vs. 127 mmHg, p < 0.001), diastolic BP (83 mmHg vs. 78 mmHg, p < 0.001), and mean arterial pressure (100 mmHg vs. 96 mmHg, p < 0.001) than females. However, all BP components per unit of BSA were significantly lower in males: daytime mean systolic BP (65 mmHg vs. 71 mmHg, p < 0.001), diastolic BP (41 mmHg vs. 44 mmHg, p < 0.001), pulse pressure (24 mmHg vs. 28 mmHg, p = 0.013), and mean arterial pressure (49 mmHg vs. 54 mmHg, p < 0.001). The same phenomenon was observed in night-time BP values. BP load per BSA is higher in women than in men, which may explain many reported sex differences in cardiovascular morbidity. Relatively small-sized individuals might benefit from a more aggressive therapeutic strategy.

Incidence and mortality of healthcare-associated infections in hospitalized patients with moderate to severe burns

PurposeThis study was to examine the incidence of different types, and isolated pathogens, of healthcare–associated infections (HAIs), and also to determine their prognostic factors for mortality. MethodsProspective surveillance was conducted in a medical center from 2005 through to 2016. Multiple logistic regression analysis was performed to assess prognostic factors of mortality. ResultsA total of 709 patients with moderate to severe burns were hospitalized. There were 83 patients (11.7%) with HAIs (158 episodes) and 203 isolated pathogens. The most common HAI types were bloodstream infection (BSI) at 39.2% (8.7% of all patients) and central line–associated BSI (mean 4.8 per 1000 central line days). Overall, S. aureus (13.8%) were the most common isolated pathogens, while the most commonly found type of multidrug-resistant pathogen was carbapenems–resistant Enterobacteriaceae (23%). The crude mortality rate was 15.7%, and the independent factors (p < .05) for mortality were BSI (Odds ratio [OR] 2.70), intensive care unit (OR 5.19) and total body surface area with full-thickness injuries ≥50% (OR 5.22). ConclusionsBurn patients with BSI were the most common HAI sites, and this was an independent factor for mortality. Effective integrated care and appropriate infection control can reduce the incidence of infection and death.

Muscle Mass and Quality of Life of Elderly People in Panti Tresna Werdha in Bandung

The proportion of elderly continues to increase from year to year due to theincrease of life expectancy. Elderly will experience degenerative process related tomuscle mass. This can disrupt the quality of life. The aim of this study was to determinethe muscle mass and quality of life (QoL) in the elderly. This study used cross sectionalapproach with the number of subjects as many as 32 elderly residents of Tresna Werdhain Bandung. The tool used to measure muscle mass is BIA Tanita SC-240 while theinstrument used in measuring quality of life is the WHOQL-BREF questionnaire. Theresult showed that the mean value of muscle mass per unit body surface area was 22.86±2.20 kg/m 2 . The highest average value of QoL is the physical domain (59.15±8,06%)while the lowest is the environmental domain (42.97±11.11%). The conclusion of thisstudy is muscle mass possessed by elderly study participants is good. The QoL isclassified as moderate.Keywords: elderly people, muscle mass, quality of life, WHOQL-BREF questionnaire

Use of Extrathoracic Deposition Models for Patient-Specific Dose Estimation during Inhaler Design.

The lung dose of inhaled pharmaceutical aerosol that an individual will receive from an inhaler can now be more accurately estimated in light of recent extrathoracic deposition modeling that has correlated characteristic airway dimensions with deposition. This paper first summarizes the current state of extrathoracic deposition models, including recent developments that have quantified the effects of aerosol electrostatics and inhaler mouthpiece diameter on deposition. A generalized equation for predicting extrathoracic deposition in different subjects is then developed and average characteristic airway dimensions representative of different age groups are indicated. A methodology is then presented to predict the lung dose per unit body surface area individuals will receive from an inhaler. A sample calculation shows that a typical 10-year-old child subject would receive a lower lung dose per unit body surface area than an adult subject inhaling through the same inhaler at the same 90 L min-1 flow rate, due to greater extrathoracic deposition in the child. In order to provide an equivalent lung dose per unit body surface area to the child as to the adult, an inhaler particle size adjustment is specified. Finally, the use of idealized geometries for developing inhaler-specific empirical correlations and improving upon inhaler design is outlined.

A computational tool for patient specific dosimetry and radiobiological modeling of selective internal radiation therapy with 90Y microspheres

In recent years we have witnessed tremendous progress in selective internal radiation therapy. In clinical practice, quite often, radionuclide therapy is planned using simple models based on standard activity values or activity administered per unit body weight or surface area in spite of the admission that radiation-dose methods provide more accurate dosimetric results. To address that issue, the authors developed a Matlab-based computational software, named Patient Specific Yttrium-90 Dosimetry Toolkit (PSYDT). PSYDT was designed for patient specific voxel-based dosimetric calculations and radiobiological modeling of selective internal radiation therapy with 90Y microspheres. The developed toolkit is composed of three dimensional dose calculations for both bremsstrahlung and beta emissions. Subsequently, radiobiological modeling is performed on a per-voxel basis and cumulative dose volume histograms (DVHs) are generated. In this report we describe the functionality and visualization features of PSYDT.

Initial catch-up growth in children with hypothyroidism on thyroxine replacement therapy

Background: There is a paucity of observational data from India on initial catch up growth in hypothyroid children started on thyroxine replacement therapy. Methods: We retrospectively studied 44 children and adolescents (32 girls) with a diagnosis of primary hypothyroidism i.e., (thyrotropin > 15 μIU/mL and thyroxine < 55ng/mL). All were started on treatment with oral thyroxine. The dose was adjusted to maintain thyrotropin between 0.5-5 μIU/mL. Height was measured at baseline and at each follow-up visit and height standard deviation scores (HtSDS) were calculated. We studied the therapeutic benefit of thyroxine replacement therapy on growth in the initial couple of years of treatment. Results: Dose of thyroxine required to restore euthyroidism was 4.1±2.5 μg/kg body weight. The dose fell from 9.7±2.4 μg/kg body weight in infants to 3.0±1.5 μg/kg body weight in adolescence (p<0.001). Likewise, the dose per unit body surface area also fell consistently from 207 ± 70.3 μg/m2 in infants to only 89.3±17.9 μg/m2 in adolescents (p<0.001). The initial HtSDS was -2.0±1.5 and this improved by 0.4 to final value of -1.6±1.3 (p < 0.001) after an average follow up of 14.1±2.5 months. The mean catch-up growth velocity, weighted for the duration of follow-up was 7.7 cm/year. Conclusions: The HtSDS deficit because of hypothyroidism is partially regained in the first few years after treatment.

The role of phenotype, body mass index, parental and sun exposure factors in the prevalence of melanocytic nevi among schoolchildren in Lithuania.

The occurrence and number of melanocytic nevi (MN) are among the most important known risk factors for the development of cutaneous melanoma (CM). To estimate the prevalence of MN among schoolchildren and its relationship with phenotype, body mass index (BMI), parental and sun exposure factors. A cross-sectional study was conducted on N = 1277 schoolchildren aged 7-19 years old in Kaunas city, Lithuania. Subjects were interviewed using a self-administered questionnaire and were assessed by a dermatologist. MN of all sizes and ≥2 mm in diameter were counted; phenotypic features and skin phototype were defined. BMI and body surface area (BSA) were calculated. Whole-body MN counts were expressed both as totals and as counts per unit of BSA - MN density (MND). Biological parents completed questionnaires regarding nevus counts, family history of skin cancer and CM. The numbers of all sizes and ≥2 mm MN increased according to age, respectively, from median values of 44 (IQR 28, 60) and 5 (IQR 2, 8) at the age of 7-9 years to 85 (IQR 55, 128) and 16 (IQR 8, 30) at the age of 16-19 years. A higher MND was found in children with light skin colour (P < 0.001), I-II skin phototype (P < 0.001), extensive facial freckling (P < 0.005) and multiple nevi on the father's and mother's arms (P < 0.05). 20.2% of pupils were overweight or obese, 130 males and 118 females. Overweight and obese children had a higher all sizes MND (P = 0.033, P = 0.044). Acquired suntan at the end of summer was associated with a higher all sizes MND (P < 0.05), outdoor activities at midday - with a higher ≥2 mm MND (P = 0.047) respectively. The prevalence of MN among schoolchildren is age-dependent and strongly determined by skin colour, skin phototype, facial freckling and BMI. Parental nevus numbers, acquired suntan and outdoor activities at midday must be considered.

Heat removal using microclimate foot cooling: a thermal foot manikin study.

It has been proposed that microclimate cooling systems exploit the peripheral extremities because of more efficient heat transfer. The purpose of this study was to quantify, using a patented microclimate cooling technique, the heat transfer from the plantar surface of the foot for comparison to other commonly cooled body regions. A military boot was fitted with an insole embedded with a coiled, 1.27 m length of hollow tubing terminating in inlet and outlet valves. A thermal foot manikin with a surface temperature of 34 degrees C was placed in the boot and the valves were connected to a system that circulated water through the insole at a temperature of 20 degrees C and flow rate of 120 ml x min(-1). The manikin foot served as a constant heat source to determine heat transfer provided by the insole. Testing was done with the foot model dry and sweating at a rate of 500 ml x h(- 1) x m(-2). Climatic chamber conditions were 30 degrees C with 30% RH. Heat loss was approximately 4.1 +/- 0.1 and approximately 7.7 +/- 0.3 W from the dry and sweating foot models, respectively. On a relative scale, the heat loss was 3.0 W and 5.5 W per 1% (unit) body surface area, respectively, for the dry and sweating conditions. The relative heat loss afforded by plantar foot cooling was similar compared to other body regions, but the absolute amount of heat removal is unlikely to make an impact on whole body heat balance.

Albumin:Creatinine Ratio – A Flawed Measure? The Merits of Estimated Albuminuria Reporting

Current guidelines illogically recommend that a different approach is taken to the correction for creatinine generation rate when estimating glomerular filtration rate (GFR) and when interpreting urine albumin:creatinine ratio (ACR). Age, gender and race are routinely used to adjust for predicted muscle mass in GFR estimation, even though estimated GFR is expressed per unit body surface area. Conversely, ACR is at most adjusted with the use of gender-specific classification thresholds. This difference is surprising since the proportional effect of muscle mass on serum and urine creatinine is identical. Failure to adjust for creatinine generation rate compromises ACR, potentially adversely affecting management decisions and mislabelling individuals as having/not having CKD. A greater ACR is also a marker of low muscle mass, which has confounding prognostic effects. Determination of the optimal method to adjust ACR for estimated muscle mass should improve its performance. Routine reporting of the resulting ‘estimated albumin excretion rate’, as for routine eGFR reporting, would remove the need for gender-specific thresholds.

Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study

Emerging evidence on body composition suggests that sarcopenic obesity (obesity with depleted muscle mass) might be predictive of morbidity and mortality in non-malignant disease and also of toxicity to chemotherapy. We aimed to assess the prevalence and clinical implications of sarcopenic obesity in patients with cancer. Between Jan 13, 2004, and Jan 19, 2007, 2115 patients with solid tumours of the respiratory or gastrointestinal tract from a cancer treatment centre serving northern Alberta, Canada, were identified. Available lumbar CT images of the obese patients were analysed for total skeletal muscle cross-sectional area; these values were also used to estimate total body fat-free mass (FFM). Of the 2115 patients initially identified, 325 (15%) were classified as obese (body-mass index [BMI] > or =30). Of these obese patients, 250 had CT images that met the criteria for analysis. The remaining 75 patients were recorded as without assessable scans. Obese patients had a wide range of muscle mass. Sex-specific cut-offs that defined a significant association between low muscle mass with mortality were ascertained by optimum stratification analysis: 38 (15%) of 250 patients who had assessable CT images that met the criteria for analysis were below these cut-offs and were classified as having sarcopenia. Sarcopenic obesity was associated with poorer functional status compared with obese patients who did not have sarcopenia (p=0.009), and was an independent predictor of survival (hazard ratio [HR] 4.2 [95% CI 2.4-7.2], p<0.0001). Estimated FFM showed a poor association with body-surface area (r(2)=0.37). Assuming that FFM represents the volume of distribution of many cytotoxic chemotherapy drugs, we estimated that individual variation in FFM could account for up to three-times variation in effective volume of distribution for chemotherapy administered per unit body-surface area, in this population. This study provides evidence of the great variability of body composition in patients with cancer and links body composition, especially sarcopenic obesity, to clinical implications such as functional status, survival, and potentially, chemotherapy toxicity.

Baby Care Products: Possible Sources of Infant Phthalate Exposure

Phthalates are man-made chemicals found in personal care and other products. Recent studies suggest that some phthalates can alter human male reproductive development, but sources of infant exposure have not been well characterized. We investigated the relationship between phthalate metabolite concentrations in infant urine and maternal reported use of dermally applied infant care products. We measured 9 phthalate metabolites in 163 infants who were born in 2000-2005. An infant was considered to have been exposed to any infant care product that the mother reported using on her infant within 24 hours of urine collection. Results of multiple linear regression analyses are reported as the ratio of metabolite concentrations (with 95% confidence intervals) in exposed and unexposed infants. We standardized concentrations by forming z scores and examined combined exposure to multiple metabolites. In most (81%) infants, > or = 7 phthalate metabolites were above the limit of detection. Exposure to lotion was predictive of monoethyl phthalate and monomethyl phthalate concentrations, powder of monoisobutyl phthalate, and shampoo of monomethyl phthalate. Z scores increased with number of products used. Most associations were stronger in younger infants. Phthalate exposure is widespread and variable in infants. Infant exposure to lotion, powder, and shampoo were significantly associated with increased urinary concentrations of monoethyl phthalate, monomethyl phthalate, and monoisobutyl phthalate, and associations increased with the number of products used. This association was strongest in young infants, who may be more vulnerable to developmental and reproductive toxicity of phthalates given their immature metabolic system capability and increased dosage per unit body surface area.

Body Composition as an Independent Determinant of 5-Fluorouracil–Based Chemotherapy Toxicity

Evidence suggests that lean body mass (LBM) may be useful to normalize doses of chemotherapy. Data from a prospective study were used to determine if the highest doses of 5-fluorouracil (5-FU) per kilogram LBM would be associated with dose-limiting toxicity in stage II/III colon cancer patients treated with 5-FU and leucovorin. Toxicity after cycle 1 was graded according to National Cancer Institute Common Toxicity Criteria, version 2.0. Muscle tissue was measured by computerized tomography. An extrapolation to the LBM compartment of the whole body was employed. Mean values of 5-FU/LBM of the entire population were different in terms of presence or absence of toxicity (P = 0.036). A cut point of 20 mg 5-FU/kg LBM seemed to be a threshold for developing toxicity (P = 0.005). This observation was pertinent to women (odds ratio, 16.73; P = 0.021). Women in this study had a relatively low proportion of LBM relative to their body surface area. Our study shows that low LBM is a significant predictor of toxicity in female patients administered 5-FU using the convention of dosing per unit of body surface area. We conclude that variation in toxicity between females and males may be partially explained by this feature of body composition.

Validation of prospective whole-body bone marrow dosimetry by SPECT/CT multimodality imaging in 131I-anti-CD20 rituximab radioimmunotherapy of non-Hodgkin?s lymphoma

Radioimmunotherapy (RIT) for relapsed non-Hodgkin's lymphoma is emerging as a promising treatment strategy. Myelosuppression is the dose-limiting toxicity and may be particularly problematic in patients heavily pretreated with chemotherapy. Reliable dosimetry is likely to minimise toxicity and improve treatment efficacy, and the aim of this study was to elucidate the complex problems of dosimetry of RIT by using an integrated SPECT/CT system. As a part of a clinical trial of (131)I-anti-CD20 rituximab RIT of non-Hodgkin's lymphoma, we employed a patient-specific prospective dosimetry method utilising the whole-body effective half-life of antibody and the patient's ideal weight to calculate the administered activity for RIT corresponding to a prescribed radiation absorbed dose of 0.75 Gy to the whole body. A novel technique of quantitation of bone marrow uptake with hybrid SPECT/CT imaging was developed to validate this methodology by using post-RIT extended imaging and data collection. A strong, statistically significant correlation (p=0.001) between whole-body effective half-life of antibody and effective marrow half-life was demonstrated. Furthermore, it was found that bone marrow activity concentration was proportional to administered activity per unit weight, height or body surface area (p<0.001). The results of this study show the proposed whole-body dosimetry method to be valid and clinically applicable for safe, effective RIT.