A randomized controlled trial of an enhanced recovery after surgery protocol in patients undergoing laparoscopic sleeve gastrectomy.

BACKGROUND: The purpose of this study was to evaluate the effect of an enhanced recovery after surgery (ERAS) protocol on opioid and anti-emetic use, length of stay and safety after laparoscopic sleeve gastrectomy (LSG). METHODS: Patients who underwent LSG between March 2018 and January 2019 at our accredited, high-volume bariatric surgery center were randomized to either standard of care (SOC) or ERAS. ERAS included a pre- and post-surgical medication regimen designed to reduce postoperative nausea, vomiting and pain. Outcomes included post-operative symptom scores, opioid use, anti-emetic use, time to achieve readiness for discharge (RFD) and inpatient and 30-day adverse events, readmissions and emergency department visits. RESULTS: The final analysis included 130 patients, (SOC 65; ERAS 65). Groups did not differ on demographics or comorbidities. Relative to SOC, fewer ERAS patients utilized opioids in the hospital ward (72.3% vs. 95.4%; p < .001), peak pain scores were significantly lower, and median time to achieve RFD was shorter (28.0 h vs. 44.4 h; p = 0.001). More ERAS patients were discharged on post-operative day 1 (38.5% vs. 15.4%; p < .05). The overall use of rescue anti-emetic medications was not different between groups. Rates of postoperative 30-day events, readmissions, and emergency department visits did not differ between groups. CONCLUSION: Relative to SOC, ERAS was associated with earlier discharge, lower pain scores, less frequent use of opioids and use in lower amounts after LSG with no differences in 30 day safety outcomes.

Utility of a Novel Scale to Assess Readiness for Discharge After Bariatric Surgery.

BACKGROUND: The safe release of a patient from hospital care after bariatric surgery depends upon the achievement of satisfactory health status. Here, we describe a new objective scale (the Readiness for Discharge, RFD Scale) to measure the patient's suitability for hospital discharge after bariatric surgery. METHODS: We conducted a retrospective, observational analysis of data collected in a randomized clinical trial of an enhanced recovery after surgery protocol for laparoscopic sleeve gastrectomy from 3/15/2018 to 1/12/2019. Nursing staff assessed 122 patients every 4-8 h after surgery using a checklist to document 5 components: ambulation, vital signs, pain, nausea, and oral intake of clear fluid. Satisfaction of each component was scored as "1" (satisfactory) or "0" (not satisfactory). Scores were summed and analyzed for patterns. RFD = 5 marked the patient as ready for discharge. RESULTS: Sufficient intake of clear liquid was the last RFD component satisfied in 87% of patients. Two overall response patterns emerged: "Steady Progressors" (n = 51) whose RFD score rose steadily from 0 to 5 without reversion to a lower score; and "Oscillators" (n = 71) who had at least one temporary decrease in RFD score on the way to attaining 5, or showed a simultaneous oscillation of components without change in RFD. CONCLUSIONS: The RFD checklist allows objective scoring of medical readiness for discharge after LSG and has the potential to improve clinical communication.

Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19.

INTRODUCTION: To compare outcomes in patients hospitalized with coronavirus (COVID-19) receiving famotidine therapy with those not receiving famotidine. METHODS: Retrospective, propensity-matched observational study of consecutive COVID-19-positive patients between February 24, 2020, and May 13, 2020. RESULTS: Of 878 patients in the analysis, 83 (9.5%) received famotidine. In comparison to patients not treated with famotidine, patients treated with famotidine were younger (63.5 ± 15.0 vs 67.5 ± 15.8 years, P = 0.021), but did not differ with respect to baseline demographics or preexisting comorbidities. Use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio 0.37, 95% confidence interval 0.16-0.86, P = 0.021) and combined death or intubation (odds ratio 0.47, 95% confidence interval 0.23-0.96, P = 0.040). Propensity score matching to adjust for age difference between groups did not alter the effect on either outcome. In addition, patients receiving famotidine displayed lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs 12.7 mg/dL, P = 0.002), lower median procalcitonin levels (0.16 vs 0.30 ng/mL, P = 0.004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs 964.0 ng/mL, P = 0.076). Logistic regression analysis demonstrated that famotidine was an independent predictor of both lower mortality and combined death/intubation, whereas older age, body mass index >30 kg/m, chronic kidney disease, National Early Warning Score, and higher neutrophil-lymphocyte ratio were all predictors of both adverse outcomes. DISCUSSION: Famotidine use in hospitalized patients with COVID-19 is associated with a lower risk of mortality, lower risk of combined outcome of mortality and intubation, and lower levels of serum markers for severe disease in hospitalized patients with COVID-19.(Equation is included in full-text article.).

Hyperleptinemia is associated with CRP, but not apolipoprotein E, and is reduced by exercise training.

The purpose of this study was to examine whether leptin levels affect the response of leptin to exercise training (ET) and whether this is also affected by C-reactive protein (CRP) or the three common Apolipoprotein E genotypes (APOE). Ninety-seven (male = 45, female = 52) sedentary individuals underwent 6 months of supervised ET. Blood was sampled before the initiation of ET, and again 24 and 72 hr after completion of the final training session. ET resulted in a small reduction in body mass (80.47 ± 18.03 vs 79.42 ± 17.34 kg, p < .01). Leptin was reduced 24 hr after the final exercise session (p < .01), but returned to normal after 72 hr (p > .05)--Pre: 13.51 ± 12.27, 24hr: 12.14 ± 12.34, 72 hr: 12.98 ± 11.40 ng/ml. The most hyperleptinemic individuals had a greater initial response, which was sustained through to 72 hr after the final session in the pooled study population (p < .01), and in both males (p < .05) and females (p < .05) separately. CRP was related to leptin independently of body weight and positively related to the reductions in leptin. APOE genotype was not related to leptin levels and did not affect the response to ET. Leptin levels may only be reduced by ET in those with hyperleptinemia. In addition, both the initial extent of hyperleptinemia and the subsequent reduction in leptin may be related to low grade chronic systemic inflammation.

Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans.

OBJECTIVE: This study was intended to determine the incidence rate of warfarin-related adverse events (e.g., bleeding) in Puerto Ricans and whether a genetic association between warfarin pharmacogenes and any of these adverse events was observed over the initiation period (i.e., the first 90 days of therapy). METHODS: We conducted an observational, retrospective cohort study of pharmacogenetic association in 122 warfarin-treated, male, Puerto Rican patients (69.9 +/- 9.6 years) from the Veterans Affair Caribbean Healthcare System (VACHS) who consented to participate. Genotyping was performed using the CYP2C9 and VKORC1 assays by Luminex. Event-free survival curves were estimated using the Kaplan-Meier method and analyzed by log-rank test. Cox regression models were constructed and hazard ratios (HR) calculated. RESULTS: Carriers of functional CYP2C9 and VKORC1 polymorphisms demonstrated a higher incidence rate of multiple adverse events (i.e., 5.2 vs. 1.0 cases per 100 patient-months; RR = 4.8, p = 0.12) than did wild types. A significant association was observed between multiple adverse events and carrier status (HR = 2.5; 95% CI: 1.0-6.3, p = 0.04). However, no significant associations between genotypes and individual outcomes over the first 90 days of therapy were found. CONCLUSION: The association of CYP2C9 and VKORC1 genotypes and risks for adverse events due to exposure to warfarin was examined for the first time in Puerto Ricans. Despite a lack of association with individual events in this study population, our findings revealed a potential utility of genotyping for the prevention of multiple adverse events during warfarin therapy.

Multimodal approach utilising a weight management programme prior to bariatric surgery in patients with BMI ≥50 kg/m2: A propensity score matching retrospective cohort study.

We evaluated preoperative weight loss and days from initial consult to surgery in patients with BMI ≥50 kg/m2 who were and were not enrolled in medical weight management (MWM) prior to laparoscopic sleeve gastrectomy. We retrospectively identified patients with BMI ≥50 kg/m2 who had primary sleeve gastrectomy between 2014 and 2019 at two bariatric surgery centres in our healthcare system. Patients presenting after 2017 that received preoperative MWM (n = 28) were compared to a historical cohort of non-MWM patients (n = 118) presenting prior to programme initiation in 2017 on preoperative percent total body weight loss (%TBWL) and days from initial consult to surgery. A total of 151 patients (MWM, 33; non-MWM, 118) met inclusion criteria. BMI was significantly greater in MWM versus non-MWM (p = .018). After propensity score matching, median BMI at initial consult in non-MWM versus MWM no longer differed (p = .922) neither were differences observed on the basis of weight, age, sex, race or ethnicity. After PSM, MWM had significantly lower BMI at surgery (p = .018), lost significantly more weight from consult to surgery (p < .001) and achieved significantly greater median %TBWL from consult to surgery (p < .001). We noted no difference between groups on 6-month weight loss (p = .533). Days from initial consult to surgery did not differ between groups (p < .863). A preoperative MWM programme integrated into multimodal treatment for obesity in patients with a BMI ≥50 kg/m2 resulted in clinically significant weight loss without prolonging time to surgery.

Acute effects of ingestion of a novel whey-derived extract on vascular endothelial function in overweight, middle-aged men and women.

Whey protein intake reduces CVD risk, but little is known whether whey-derived bioactive peptides regulate vascular endothelial function (VEF). We determined the impact of a whey-derived extract (NOP-47) on VEF in individuals with an increased cardiovascular risk profile. Men and women with impaired brachial artery flow-mediated dilation (FMD) (n 21, age 55 (sem 1·3) years, BMI 27·8 (sem 0·6) kg/m2, FMD 3·7 (sem 0·4) %) completed a randomised, cross-over study to examine whether ingestion of NOP-47 (5 g) improves postprandial VEF. Brachial artery FMD, plasma amino acids, insulin, and endothelium-derived vasodilators and vasoconstrictors were measured for 2 h after ingestion of NOP-47 or placebo. Acute NOP-47 ingestion increased FMD at 30 min (4·6 (sem 0·5) %) and 120 min (5·1 (sem 0·5) %) post-ingestion (P< 0·05, time × trial interaction), and FMD responses at 120 min were significantly greater in the NOP-47 trial compared with placebo (4·3 (sem 0·5) %). Plasma amino acids increased at 30 min following NOP-47 ingestion (P< 0·05). Serum insulin increased at 15, 30 and 60 min (P< 0·001) following NOP-47 ingestion. No changes were observed between the trials for plasma NO∙ and prostacyclin metabolites or endothelin-1. Ingestion of a rapidly absorbed extract derived from whey protein improved endothelium-dependent dilation in older adults by a mechanism independent of changes in circulating vasoactive compounds. Future investigation is warranted in individuals at an increased CVD risk to further elucidate potential health benefits and the underlying mechanisms of extracts derived from whey.

Incidence of Hiatal Hernia Repair During Primary Bariatric Surgery Conversion: an Analysis of the 2020 MBSAQIP Database.

The rate of hiatal hernia (HH) repair during conversion bariatric surgery is largely unknown. We sought to determine this rate in 12,788 patients undergoing conversion surgery using the 2020 participant use file of the MBSAQIP database. Concurrent HH repair was performed in 24.1% of conversion cases; most commonly during SG to RYGB (33.1%), followed by AGB to SG conversion (20.2%). The remaining conversion pathways had a repair rate around 13%. Only 12.1% of HH repairs were performed using a mesh. GERD was the primary indication for conversion in 65% of the SG to RYGB cases. A much higher proportion of patients with concomitant HH repair reported GERD as the main reason for conversion than those without a HH repair (44.5% vs. 23.7%; p<0.001).

Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes.

BACKGROUND: The influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients. OBJECTIVE: To test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm. METHODS: A retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested. RESULTS: Sixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients. CONCLUSIONS: This study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA-guided warfarin dosing algorithm.

CYP2C19 genotype-guided antiplatelet therapy in a patient with clopidogrel resistance.

We report a switch in antiplatelet medication based on platelet function and CYP2C19 genotype test results in a 74-year-old man with severe coronary arterial disease. Upon bare metal stent implantation at age 66, clopidogrel therapy (75 mg/ day) was initiated to supplement aspirin. Over the next eight years, the patient required multiple percutaneous coronary interventions for de novo coronary stenosis and in-stent restenosis. Platelet reactivity measured while on clopidogrel therapy was high, consistent with clopidogrel resistance. CYP2C19 genotype testing then revealed homozygosity for the *2 null allele. The *2/*2 designation indicates poor metabolizer status, indicating deficient capacity of the cytochrome p450 2C19 enzyme for activation of clopidogrel. A medication switch to prasugrel,which does not rely on activation by the 2C19 enzyme, reduced platelet reactivity by 86%. The patient has suffered no cardiovascular events in the 18 months since initiation of prasugrel therapy.

AKT1 polymorphisms are associated with risk for metabolic syndrome.

Converging lines of evidence suggest that AKT1 is a major mediator of the responses to insulin,insulin-like growth factor 1 (IGF1), and glucose. AKT1 also plays a key role in the regulation of both muscle cell hypertrophy and atrophy. We hypothesized that AKT1 variants may play a role in the endophenotypes that makeup metabolic syndrome. We studied a 12-kb region including the first exon of the AKT1 gene for association with metabolic syndrome-related phenotypes in four study populations [FAMUSS cohort (n = 574; age 23.7 ± 5.7 years), Strong Heart Study (SHS) (n = 2,134; age 55.5 ± 7.9 years), Dynamics of Health, Aging and Body Composition (Health ABC) (n = 3,075; age 73.6 ± 2.9 years), and Studies of a Targeted Risk Reduction Intervention through Defined Exercise (STRRIDE)(n = 175; age 40­65 years)]. We identified a three SNP haplotype that we call H1, which represents the ancestral alleles eles at the three loci and H2, which represents the derived alleles at the three loci. In young adult European Americans (FAMUSS), H1 was associated with higher fasting glucose levels in females. In middle age Native Americans (SHS), H1 carriers showed higher fasting insulin and HOMA in males, and higher BMI in females. Inolder African-American and European American subjects(Health ABC) H1 carriers showed a higher incidence of metabolic syndrome. Homozygotes for the H1 haplotype showed about twice the risk of metabolic syndrome in both males and females (p < 0.001). In middle-aged European Americans with insulin resistance (STRRIDE) studied by intravenous glucose tolerance test (IVGTT), H1 carriers showed increased insulin resistance due to the Sg component (p = 0.021). The 12-kb haplotype is a risk factor for metabolic syndrome and insulin resistance that needs to be explored in further populations.

Case Report: Off Label Utilization of Topiramate and Metformin in Patients With BMI ≥50 kg/m2 Prior to Bariatric Surgery.

FDA approved anti-obesity medications may not be cost effective for patients struggling with pre-operative weight loss prior to bariatric surgery. Metformin, a biguanide, and Topiramate, a carbonic anhydrase inhibitor, both cost effective medications, have demonstrated weight loss when used for the treatment of type 2 diabetes or seizures, respectively. The aim of the three cases is to demonstrate the clinical utility of topiramate and metformin for preoperative weight loss in patients with a body mass index (BMI) ≥ 50 kg/m2 prior to bariatric surgery who are unable to follow the bariatric nutritional prescription due to a dysregulated appetite system Each patient was prescribed metformin and/or topiramate in an off-label manner in conjunction with lifestyle modifications and achieved >8% total body weight loss during the preoperative period.

C Peptide Fails to Improve the Utility of the DiaRem Algorithm in Predicting Remission of Type II Diabetes After Bariatric Surgery.

We evaluated the utility of C peptide as an addition to the DiaRem score for predicting type 2 diabetes (T2D) remission 1 year after bariatric surgery in 175 patients. DiaRem score was significantly correlated with C peptide (r = - .43; p < .001). Both DiaRem and C peptide were significant predictors of remission of T2D (OR (95% CI) = .81 (.75-.86); p < 0001 and OR (95% CI) = 1.35 (1.15-1.60); p < .001, respectively). ROC analysis indicated that DiaRem was a significantly stronger predictor than C peptide (p < .001). Hierarchical regression indicated that C peptide failed to significantly improve the prediction of diabetes remission after accounting for DiaRem (OR (95% CI) = 1.079 (.87-1.26); p = .406). This study does not support the inclusion of C peptide in the DiaRem algorithm.

A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study.

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, -C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70-79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females.

Exposure to non-therapeutic INR in a high risk cardiovascular patient: potential hazard reduction with genotype-guided warfarin (Coumadin) dosing.

A case to illustrate the utility of genetic screening in warfarin (Coumadin) management is reported. A 45 year-old woman of Puerto Rican ancestry was admitted to the emergency room twice within one month with chest pain. She was diagnosed with congestive heart failure, which was stabilized both times. At her second release, warfarin therapy was initiated at 5 mg/ day to prevent thrombus formation and was lowered to 3.75 mg/day at day 7 by her primary physician. International Normalized Ratio (INR) test results in the follow-up period at days 1, 7, and 10 of warfarin therapy were 4.5, 6.5, and 7.3, respectively-far in excess of the therapeutic range, despite the lower dosage in effect from day 7 onward. The patient achieved target INR over the next 43 days after downward adjustment of the dose to a dose of 1.5 mg/day by trial and error. DNA-typing specific for the CYP2C9*2,*3,*4,*5,*6 alleles and seven variants in the VKORC1 gene, including the VKORC1-1639 G > A polymorphism, revealed the presence of combinatorial CYP2C9*2/*3 and VKORC1-1639 G/A genotypes in this patient. Entering the patient's demographic and genotype status data into independent algorithms available in the public domain to predict effective warfarin dose yielded predicted doses which ranged from 1.5 to 1.8 mg/day. Notably, the prediction of 1.5 mg/day, which was generated by the online resource www.warfarindosing.org, coincided with the patient's actual effective warfarin dose. We conclude that the rapid rise in INR observed upon the initiation of warfarin therapy and the final effective warfarin dose of 1.5 mg/day, are attributable in some part to the presence of two minor alleles in CYP2C9, which together significantly reduce warfarin metabolism. Warfarin genotyping can therefore inform the clinician of the predicted effective warfarin dose. The results highlight the potential for warfarin genetic testing to improve patient care.

Use of an Endoscopic Suturing Platform for the Management of Staple Line Dehiscence After Laparoscopic Sleeve Gastrectomy.

BACKGROUND: Management of staple line dehiscence following laparoscopic sleeve gastrectomy (LSG) varies based on local expertise and timing of presentation. We present our experience with an endoscopic suturing platform to treat patients with staple line dehiscence following LSG. METHODS: We included all patients who presented to our institution with a staple line dehiscence following LSG from 2005 through November 2017. All endoscopic suturing procedures were performed by a single interventional endoscopist. RESULTS: Five patients, ages 25-69 years, received treatment of staple line dehiscence at a median time of 22 days following LSG (range 13-335 days). Four out of the five patients received a stent at some point during their treatment. One patient with a chronic leak required gastrectomy and esophago-jejunostomy as a definitive treatment. The remaining four patients experienced resolution of the leak at a median of 48 days post-operatively (range 21-82 days). CONCLUSION: Endoscopic suturing may have a role in the management of leaks following LSG, as a primary treatment or as an adjunct to treatment with a stent. However, given that the technique requires considerable endoscopic expertise and in light of a number of other available therapeutic choices, further studies are required to better define the role of this technology in the algorithm of LSG-related leak management.

Acute ingestion of a novel whey-derived peptide improves vascular endothelial responses in healthy individuals: a randomized, placebo controlled trial.

BACKGROUND: Whey protein is a potential source of bioactive peptides. Based on findings from in vitro experiments indicating a novel whey derived peptide (NOP-47) increased endothelial nitric oxide synthesis, we tested its effects on vascular function in humans. METHODS: A randomized, placebo-controlled, crossover study design was used. Healthy men (n = 10) and women (n = 10) (25 +/- 5 y, BMI = 24.3 +/- 2.3 kg/m2) participated in two vascular testing days each preceded by 2 wk of supplementation with a single dose of 5 g/day of a novel whey-derived peptide (NOP-47) or placebo. There was a 2 wk washout period between trials. After 2 wk of supplementation, vascular function in the forearm and circulating oxidative stress and inflammatory related biomarkers were measured serially for 2 h after ingestion of 5 g of NOP-47 or placebo. Macrovascular and microvascular function were assessed using brachial artery flow mediated dilation (FMD) and venous occlusion strain gauge plethysmography. RESULTS: Baseline peak FMD was not different for Placebo (7.7%) and NOP-47 (7.8%). Placebo had no effect on FMD at 30, 60, and 90 min post-ingestion (7.5%, 7.2%, and 7.6%, respectively) whereas NOP-47 significantly improved FMD responses at these respective postprandial time points compared to baseline (8.9%, 9.9%, and 9.0%; P < 0.0001 for time x trial interaction). Baseline reactive hyperemia forearm blood flow was not different for placebo (27.2 +/- 7.2%/min) and NOP-47 (27.3 +/- 7.6%/min). Hyperemia blood flow measured 120 min post-ingestion (27.2 +/- 7.8%/min) was unaffected by placebo whereas NOP-47 significantly increased hyperemia compared to baseline (29.9 +/- 7.8%/min; P = 0.008 for time x trial interaction). Plasma myeloperoxidase was increased transiently by both NOP-47 and placebo, but there were no changes in markers inflammation. Plasma total nitrites/nitrates significantly decreased over the 2 hr post-ingestion period and were lower at 120 min after placebo (-25%) compared to NOP-47 (-18%). CONCLUSION: These findings indicate that supplementation with a novel whey-derived peptide in healthy individuals improves vascular function.

Prevalence of combinatorial CYP2C9 and VKORC1 genotypes in Puerto Ricans: implications for warfarin management in Hispanics.

Polymorphisms in the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes significantly alter the effective warfarin dose. We determined the frequencies of alleles, single carriers, and double carriers of single nucleotide polymorphisms (SNPs) in the CYP2C9 and VKORC1 genes in a Puerto Rican cohort and gauged the impact of these polymorphisms on warfarin dosage using a published algorithm. A total of 92 DNA samples were genotyped using Luminex x-MAP technology. The polymorphism frequencies were 6.52%, 5.43% and 28.8% for CYP2C9 *2, *3 and VKORC1-1639 C>A polymorphisms, respectively. The prevalence of combinatorial genotypes was 16% for carriers of both the CYP2C9 and VKORC1 polymorphisms, 9% for carriers of CYP2C9 polymorphisms, 35% for carriers of the VKORC1 polymorphism, and the remaining 40% were non-carriers for either gene. Based on a published warfarin dosing algorithm, single, double and triple carriers of functionally deficient polymorphisms predict reductions of 1.0-1.6, 2.0-2.9, and 2.9-3.7 mg/day, respectively, in warfarin dose. Overall, 60% of the population carried at least a single polymorphism predicting deficient warfarin metabolism or responsiveness and 13% were double carriers with polymorphisms in both genes studied. Combinatorial genotyping of CYP2C9 and VKORC1 can allow for individualized dosing of warfarin among patients with gene polymorphisms, potentially reducing the risk of stroke or bleeding.

Association of age with muscle size and strength before and after short-term resistance training in young adults.

The purpose of this study was to assess the association of age with muscle mass and strength in a group of young adults before and after 12 weeks of progressive resistance training. Eight hundred twenty-six young males and females (age 24.34 +/- 5.69 yr, range 18-39 yr) completed a strictly supervised 12-week unilateral resistance training program of the nondominant arm. Isometric (maximal voluntary contraction [MVC]) and dynamic strength (1 repetition maximum [1RM]) of the elbow flexors and cross-sectional area (CSA) of the biceps-brachii using magnetic resonance imaging (MRI) scans were measured before and after training. Pearson correlation coefficients were calculated for size and strength variables and age. In addition, the cohort was divided into groups according to decade of life and differences assessed by analysis of variance. Age correlated significantly and positively with all pretraining measures of muscle size and strength (CSA: r = 0.191, p < 0.001; MVC: r = 0.109, p = 0.002; 1RM: r = 0.109, p = 0.002). Age was not related to the training-induced changes in CSA or MVC but was negatively associated with the change in 1RM (r = -0.217, p < 0.001). The study indicates that age does have a significant positive relationship with muscle size and strength in untrained young adults. Although age was negatively associated with improvements in 1RM, the effect of age was small relative to the improvements induced through resistance training, thus suggesting age does not limit response to training in any practical way during early adulthood.