Robotic versus Laparoscopic Sigmoid Colectomy: Analysis of Healthcare Cost and Utilization Project Database.

Minimally invasive sigmoid colectomy via the laparoscopic approach (LA) has numerous benefits. We seek to compare outcomes between laparoscopic and robotic sigmoid colectomies. We analyzed the data using the National Inpatient Sample database between 2008 and 2014. Utilization and outcome measures were compared. The seven-year average number of patients who underwent elective sigmoid colectomy in the United States from 2008 to 2014 was estimated to be 197,053. Of these, 95.1 per cent were conducted using the LA. The mean age was 58.33 + 13.6 years and 58.23 + 12.8 years in laparoscopic and robotic approaches, respectively. No significant differences existed in respect to morbidities. Postoperative complications were comparable with respect to other complications. Length of hospital stay was statistically significantly shorter in the robot-assisted approach compared with the LA (mean 4.8 + 4 vs 5.7 + 5 days, respectively, P < 0.001). Patients who underwent robotic surgery had significantly higher total hospital charges than those who underwent laparoscopic surgery (median $45,057 vs $57,871 USD, P < 0.001). The advent of robot-assisted surgery has provided more options for patients and surgeons. Compared with laparoscopy, robot-assisted sigmoid colectomy has no clinical advantages in morbidity and mortality. However, the robotic approach has a significantly higher total charge to the patient.

Renal Transplantation Is Associated with Increased Complications Following Spinal Fusion Operations: Analysis of a National Database.

BACKGROUND: Improved postoperative care for renal transplant recipients has advanced both duration and overall quality of life. However, degenerative spinal pathology is increasingly prevalent after transplant. Outcomes following spinal fusion among the renal transplant population in the United States are rarely addressed. METHODS: The Healthcare Cost and Utilization Project National Inpatient Sample database was employed. Cases in years 2008-2014 for patients ≥18 years old receiving spinal fusion, exploration/decompression, and/or spinal revision/re-fusion surgeries were included. Cases were divided into kidney transplant recipients (KTR) and non-kidney transplant recipients. Complications, demographics, and socioeconomic outcomes were compared between cohorts. RESULTS: Of 579,726 patients who met inclusion criteria, 685 (0.1%) were KTRs. The KTR population was older and included more men compared with the non-kidney transplant recipient population (60.1 years vs. 56.6 years, P < 0.001; 58% male vs. 45.5% male, P < 0.001). KTRs experienced higher total complication rates (29.8% vs. 18.9%, P < 0.001). Prevalence of acute posthemorrhagic anemia and need for transfusion was markedly higher for KTRs (15.8% vs. 9.1%, P < 0.001; 13.6% vs. 6.2%, P < 0.001). Multivariate analysis revealed longer length of stay (median 1.23 days, interquartile range 0.94-1.53, P < 0.001), lower routine discharge (odds ratio = 0.57, 95% confidence interval 0.48-0.69, P < 0.001), and higher discharge to alternative care facilities (odds ratio = 1.91, 95% confidence interval 1.57-2.33, P < 0.001) for KTRs. The inpatient course for KTRs undergoing spinal operations was significantly costlier ($87,445 vs. $71,589, P < 0.001). CONCLUSIONS: History of renal transplant was associated with increased inpatient medical and socioeconomic complications following spinal fusion. Physicians and patients must understand and respect the potentially increased perioperative challenges facing KTRs.

Burn patients with history of kidney transplant experience increased incidence of wound infection.

OBJECTIVE: To determine if history of kidney transplant is an independent risk factor for increased incidence of wound infection and other morbidities in burn patients. BACKGROUND: While the goal of immunosuppression post-organ transplantation is to prevent graft rejection, it is often associated with significant adverse effects such as increased susceptibility to infection, drug toxicity, and malignancy. Burn injuries lead to a dysregulated hypermetabolic state and a compromised cutaneous barrier, which predisposes to infection and delayed wound healing. We surmise that a history of kidney transplant increases the risk of wound infection in in-hospital burn victims. METHODS: A retrospective analysis was performed on 57,948 adults diagnosed in-hospital with a burn injury between 2008-2014, obtained from the Nationwide Inpatient Sample (NIS) by Healthcare Cost and Utilization Project (HCUP). RESULTS: 103 burn victims (0.2%) with a history of kidney transplant (KTX) were identified. Compared to burn patients without a history of transplant (No-KTX), they were older (54.3 ± 13.8 vs 49.8 ± 18.7; p = 0.001), more likely be insured under Medicare (69.9% vs 31.1%; p < 0.001), and less likely to have Medicaid (5.8% vs 17.2%; p = 0.002). Higher in-hospital mortality index scores were observed in KTX compared to no-KTX with p < 0.001. The incidence rates of complications such as wound infection (33.0 vs 16.3; p < 0.001) and acute renal failure (18.4 vs 7.7; p < 0.001) were significantly higher in the KTX group. After adjusting for confounding factors in multivariable analysis, the incidence of wound infection remained significantly higher. Burn patients with history of KTX were not more likely to be treated at a transplant (TX) center. TX centers were determined to have higher mortality rate, longer length of stay, and higher total hospital charges. CONCLUSION: History of kidney transplant is an independent risk factor for increased incidence of wound infection in burn patients.

Patients with Parkinson Disease Experience Increased Perioperative Complications Following Cervical Decompression and Fusion: A Retrospective Review of the National Inpatient Sample.

BACKGROUND: Despite improved medical management, the incidence of spinal pathology remains high in patients with Parkinson disease (PD). Several studies have investigated lumbar spine surgery in this population, but data regarding costs and perioperative complications for patients undergoing cervical decompression/fusion on a nationwide scale are lacking. METHODS: Cases of cervical spinal decompression, fusion, or exploration in years 2008-2014 were collected via the Healthcare Cost and Utilization Project National Inpatient Sample. Demographics, complications, outcome, and total charges were compared in patients with and without PD (NPD). Confounding variables were identified for multivariate analysis. RESULTS: Data were available for 195,341 cervical spine cases, of which PD was prevalent in 779 cases (0.4%). Cases with PD experienced greater overall complication rates (12.5 vs. 7.6%; P < 0.001). Multivariate analysis revealed longer lengths of stay for the PD cohort (mean = 1.21 days longer; P < 0.001) and decreased routine discharge (odds ratio = 0.308; P < 0.001). There was no significant difference in mean total charges between PD and NPD (-$1532; P = 0.337). Mortality rates did not significantly differ for either group. CONCLUSIONS: Although patients with PD experience greater complication rates and non-home discharges following cervical spine surgery compared with NPD patients, the overall clinical impact of these results may be minimal relative to surgery at other spinal levels in this population.

Robotic Surgery Is More Expensive with Similar Outcomes in Sleeve Gastrectomy: Analysis of the NIS Database.

The aim of this study was to compare postoperative outcomes after robotic-assisted and laparoscopic bariatric sleeve gastrectomy (SG). Sleeve gastrectomy is traditionally performed using laparoscopic techniques. Robotic-assisted surgery enables surgeons to perform minimally invasive SG, but with unknown benefits. Using a national database, we compared postoperative outcomes after laparoscopic SG and robotic-assisted SG. National data from individuals undergoing elective SG in the National Inpatient Sample database between 2011 and 2013 were analyzed. Propensity score matching was used to match robotic and laparoscopic groups by demographics, comorbidities, and hospital characteristics. The matching cohorts were compared. A total of 26,195 patients who underwent elective SG for morbid obesity were included. Of these, 25,391 (96.9%) were completed via laparoscopy, whereas 804 (3.1%) were performed with robotic assistance. There were no significant differences in demographics and subsequent postoperative complications. The inhospital mortality was similar. Length of hospital stay was statistically different, with a mean of 1.88 in laparoscopic versus 2.08 days in robotic (P < 0.001). Higher total hospital charges were noted in the robotic-assisted SG group (median US$38,569 vs US$54,658, P < 0.001). These differences were evident even after adjusting for confounding factors: wound infection, atelectasis, bowel obstruction, pneumonia, and bowel obstruction (P < 0.001).

Alemtuzumab Induction Is Associated With an Equalization of Outcomes Between White and African American Kidney Transplant Recipients.

OBJECTIVES: Our aim was to assess outcomes in White and African American kidney transplant recipients after induction with alemtuzumab. MATERIALS AND METHODS: We performed a retrospective study of 464 patients who received deceased-donor kidney transplants and were induced with alem-tuzumab between March 2006 and May 2015. We evaluated ethnic influences on patient and graft survival, delayed graft function, allograft failure, and rejection. RESULTS: There were 337 White (67.3%) and 127 African American (25.3%) patients. We observed no significant differences in 1-, 3-, 5-, and 7- year death-censored graft survival. We also observed no significant differences in 1-, 3-, and 5-year patient survival rates. Having African American ethnicity was not a significant predictor of rejection, graft survival, or patient survival. CONCLUSIONS: Our results indicate that recipient ethnicity is not a predictor of rejection, graft survival, or patient survival. White and African American kidney transplant recipients induced with alemtuzumab experienced an equalization of outcomes.

Pressure Ulcers in the United States' Inpatient Population From 2008 to 2012: Results of a Retrospective Nationwide Study.

Pressure ulcers are common, increase patient morbidity and mortality, and costly for patients, their families, and the health care system. A retrospective study was conducted to evaluate the impact of pressure ulcers on short-term outcomes in United States inpatient populations and to identify patient characteristics associated with having 1 or more pressure ulcers. The US Nationwide Inpatient Sample (NIS) database was analyzed using the International Classification of Disease, 9th Revision, Clinical Modification (ICD-9 CM) diagnosis codes as the screening tool for all inpatient pressure ulcers recorded from 2008 to 2012. Patient demographics and comorbid conditions, as identified by ICD-9 code, were extracted, along with primary outcomes of length of stay (LOS), total hospital charge (TC), inhospital mortality, and discharge disposition. Continuous variables with normal distribution were expressed in terms of mean and standard deviation. Group comparisons were performed using t-test or ANOVA test. Continuous nonnormal distributed variables such as LOS and TC were expressed in terms of median, and nonparametric tests were used to compare the differences between groups. Categorical data were presented in terms of percentages of the number of cases within each group. Chi-squared tests were used to compare categorical data in different groups. For multivariate analysis, linear regressions (for continuous variable) and logistic regression (for categorical variables) were used to analyze the possible risk factors for the investigated outcomes of LOS, TC, inhospital mortality, and patient disposition. Coefficients were calculated with multivariate regression with all included patients versus patients with pressure ulcers alone. The 5-year average number of admitted patients with at least 1 pressure ulcer was determined to be 670 767 (average overall rate: 1.8%). Statistically significant differences between patients with and without pressure ulcers were observed for median LOS (7 days [mean 11.1 ± 15] compared to 3 days [mean 4.6 ± 6.8]) and median TC ($36 500 [mean $72 000 ± $122 900] compared to $17 200 [mean $32 200 ± $57 500]). The mortality rate in patients with a pressure ulcer was significantly higher than in patients without a pressure ulcer (9.1% versus 1.8%, OR = 5.08, CI: 5.03-5.1, P <0.001). Pressure ulcers were significantly more common in patients who were older or had malnutrition. The results of this study confirm the importance of prevention initiatives to help reduce the negative impact of pressure ulcers on patient outcomes and costs of care.

Trends in bariatric surgery from 2008 to 2012.

BACKGROUND: Obesity is a global epidemic that has been increasing in prevalence. The only treatment method for durable weight loss is bariatric surgery. The aim of this study was to observe trends in usage and outcomes of bariatric operations used in the United States from 2008 to 2012. METHODS: Analysis was performed on bariatric surgery admissions from 2008 to 2012 based off of the Nationwide Inpatient Sample database. Data were selected from using International Classification of Disease, 9th Revision codes correlating to bariatric procedures for the purpose of obesity. Annual estimates and trends were reviewed for patient demographics, procedure type, patient outcomes, and length of stay (LOS). RESULTS: A total of 598,756 bariatric procedures were examined. Laparoscopic gastric bypass was the most commonly used surgical method in 2008 (58.2%). A decreasing trend in its use, and the use of laparoscopic gastric banding (LGB), was equipoised with increasing use of laparoscopic sleeve gastrectomy (LSG). Use of LSG accounted for 8.2% of procedures in 2011 and 39.6% in 2012. LGB and LSG had the lowest rates of complications, in-hospital morbidity and mortality, and the shortest LOS whereas open bypass and duodenal switch had the highest rates of complications, in-hospital morbidity and mortality, and longest LOSs. Overall rates of venous thromboembolism increased from .08% in 2008 to .215% in 2012. Respiratory complications decreased from 6.1% to 3.9%. There were no observed trends in rates of renal complications, visceral injury, bleeding, and infections. In-hospital morbidity decreased, whereas mortality rates were stable at .1%. CONCLUSIONS: The utilization of bariatric procedures has reached a plateau in the United States. Changes in the composition of procedural types suggest that LSG has become a popular alternative to gastric bypass and LGB.

Epidemiology of severe sepsis: 2008-2012.

INTRODUCTION: Severe sepsis continues to be a significant burden on society. METHODS: Using the International Classification of Diseases, Ninth Revision, Clinical Modification codes, we analyzed the Healthcare Cost and Utilization Project National Inpatient Sample in order to estimate epidemiologic trends of severe sepsis from the years 2008 to 2012. The 2010 US Census, which included 308,745,538 individuals, was used to calculate incidence per 100,000 persons. RESULTS: There were a total of 6,067,789 discharges for severe sepsis. The annual incidence increased from 346/100,000 to 436/100,000 persons (P < .05). Individuals with 3 or greater organ system failures increased from 31.6% to 35.5% (P < .05), and they accounted for 57.2% to 66.7% of the total number of deaths. Overall mortality decreased from 22.2% to 17.3% (P < .05). Length of stay decreased from 9 to 7 days (P < .05). Those discharged to home with and without home-health increased (23%-27%; P < .05), but those discharged to skilled nursing facilities remained the same (35%). CONCLUSIONS: The incidence of severe sepsis continues to increase, whereas mortality decreases. However, one third of patients (those with ≥3 organ system failures) account for two thirds of the total number of deaths. More people are discharged home, whereas stable numbers go to facilities.

Meniere's disease: importance of socioeconomic and environmental factors.

STUDY OBJECTIVES: 1. Describe the prevalence of Meniere's disease in the United States. 2. Recognize important patient and environmental factors in Meniere's disease. METHODS: • Discharge data from the Nationwide Inpatient Sample, the largest US all-payer inpatient care database was analyzed for Meniere's disease between 2008 and 2010 in patients > 10 years old. Patient characteristics including prevalence, age, sex, race, household income, and geographic location were studied to determine any correlation with disease prevalence. • T-test, Chi-square and logistic regression testing was used to compare the differences between groups for continuous and categorical data. RESULTS: • The lower limit of Meniere's prevalence in the United States population was 73 per 100,000, females 84 per 100,000 compared to 56 per 100,000 among males (OR = 1.51, 95% CI 1.48-1.54, P < 0.01). • Prevalence was highest in Caucasians 91 per 100,000, and was significantly higher than other ethnic groups (P < 0.05). • Prevalence increased as age with the highest prevalence found in 81-90 year age group. • Midwest prevalence (94 per 100,000) was significantly higher than other regions (P < 0.001). • Meniere's is more common in less populated locations and the prevalence decreased as population increased. • Meniere's prevalence increased with household income. The highest prevalence was found among the 76th-100th quartile with rates of 86 per 100,000 for MD. CONCLUSIONS: Environmental factors, race and ethnicity, gender and age appear to be important factors in the prevalence of Meniere's disease.

A single center experience with retrievable IVC filters.

OBJECTIVE: To evaluate retrievable IVC filters in our institution and assess their retrieval following a well-structured follow up program. DESIGN: Retrospective cohort study. MATERIALS: The medical records of patients implanted with retrievable IVC filters were reviewed. METHODS: All retrievable filter insertions between July 2007 and August 2011 at our institution were reviewed. Data was analyzed for age, gender, indication, complications, retrieval rate, and brand of filter inserted. Statistical analysis was done using SPSS software v19. Chi-square was used to compare discrete data and t-test for continuous data. P < 0.05 was significant. RESULTS: A total of 484 patients were reviewed of which 258 (53.1%) had a complete medical record. And 96 (37.2%) filters were placed as permanent at the time of insertion. An additional 40 (15.5%) filters were converted to permanent (total permanent filters 136; 52.7%). Death was reported in 26 (10%) patients and 96 (37.2%) out of the remaining 232 patients presented for potential retrieval. Also, 73 (28.2%) had an attempt to retrieve the filters, 69 (94.5%) were successful and 4 (5.4%) failed to retrieve. The remaining 23 (8.9%) patients declined retrieval. Filters studied include Celect (38%), Bard (31.4%), Option (26.2%), Tulip (4.1%), and Recovery (0.2%). Bard was more commonly used as a retrievable filter (80.9%). Retrieval on the first attempt was 90.4% (n = 66) successful. Of the remaining seven filters, three were successfully retrieved on a second attempt, and four failed to retrieve due to filter tilt. The success rates of retrieval for Celect and Tulip were significantly lower than for Bard (p = 0.04 and 0.023, respectively). CONCLUSION: Our study showed that a variety of IVC filters can be retrieved successfully with minimal complication rates. In more than half of our patients, IVC filters were used as permanent. Failure of retrieval was most frequently due to filter tilting.

Patient variables impacting hospital costs from 2008 to 2010.

BACKGROUND: Studying the variables associated with the increased costs of health care provides valuable insight. METHODS: A review and analysis of the pertinent variables and information collected for 118.3 million hospital admissions recorded as Nationwide Inpatient Samples database was done for the years 2008 to 2010. We used hospital charges as an approximation of costs in the analysis of the patient variables and other factors contributing to hospital costs. RESULTS: The top 5 factors with the most impact on charges were diagnostic category, length of stay, number of procedures, major operating room procedures, and ownership of the hospital. CONCLUSION: The top 5 factors with the most impact on charges were length of stay, number of procedures, major diagnostic category, major operating room procedures, and ownership of the hospital.

Elevated plasma total cholesterol level is associated with the risk of asymptomatic intracranial arterial stenosis.

BACKGROUND: Intracranial arterial stenosis (ICAS) is one of the most common causes of stroke, and dyslipidemia was one of the most common risk factors related to ICAS. However, the correlation between the plasma total cholesterol level (PTC) and ICAS, especially asymptomatic ICAS (AICAS) is not clear. MATERIALS AND METHODS: 5,300 participants were enrolled in this study. The diagnosis of AICAS was made by transcranial Doppler ultrasonography. The participants were then divided into 5 essentially equal-sized groups based on their PTC levels. The multivariate logistic regression was used to analyze the correlation between the PTC level and the prevalence of AICAS. RESULTS: 13.0% of the participants were diagnosed with AICAS. The prevalence of AICAS gradually increased with the increasing PTC level. After adjusted by the possible confounding factors, the Odds Ratios (OR) of the AICAS prevalence between the 1st quintile group and the other 4 groups were 1.13, 1.23, 1.63 and 1.75 with 95% confident intervals (CI) of 0.84-1.52, 0.91-1.66, 1.20-2.22 and 1.23-2.47, respectively. The further subgroup analysis revealed that the PTC level was stronger for males (OR 1.42 95%CI 1.23-1.64), regarding the prevalence of AICAS. CONCLUSIONS: In this large community-based study, the prevalence of AICAS is 13.0%, subjects with higher PTC levels showed a mild increase in the prevalence of AICAS. The PTC level is an independent risk factor of AICAS. Males seem to be significantly more vulnerable to the risk of AICAS.

The evaluation of national time trends, quality of care, and factors affecting the use of minimally invasive breast biopsy and open biopsy for diagnosis of breast lesions.

BACKGROUND: Minimally invasive breast biopsy is a recommended biopsy method for suspicious lesions. This study examines national trends and factors associated with the use of open breast biopsy (OBB). METHODS: The national inpatient sample database was used to examine trends and factors associated with the use of OBB. Factors associated with OBB were evaluated using chi-square test for univariate analysis and logistic regression for multivariate analysis. RESULTS: OBB rate was 34%. Patients below 50 years of age had OBB rates of 47%, while those above 50 had OBB rates of 29.1% (P < .001). Higher OBB rates were observed in Asian (39.8%) and Hispanic (40.6%) women compared with white women (34.1%, P < .001). Private insurance patients were more likely to have OBB compared with Medicaid/Medicare patients (40.9% vs 30.6%, P < .001). About 1.2% of women who underwent OBB required multiple biopsies for diagnosis compared with .5% for minimally invasive breast biopsy (P < .001). CONCLUSIONS: OBB is still performed in one third of women despite higher morbidity and less accuracy. Factors associated with higher OBB rate included younger age; Asian ethnicity; private insurance; small, rural, and nonteaching hospitals.

Effect of insurance payer status on the surgical treatment of early stage breast cancer: data analysis from a single health system.

The effect of insurance payer status on surgical treatment of early stage breast cancer is unclear. This retrospective study examined the effect of insurance payer on mastectomy rates of 1539 women treated within a single health system. Women with Medicaid had significantly larger tumors compared with those with private insurance (PI) at diagnosis (3.3 cm vs 2.1 cm, P < .05) and were more likely to be treated with mastectomy for larger tumors compared with women with PI. However, women with PI were more likely to have mastectomy for smaller tumors; among women with tumors less than 2 cm, 11% with Medicaid underwent mastectomy compared with 47% with PI (P < .05). Overall, when compared with those with PI, women with Medicaid were more likely to receive mastectomy (60% vs 39%, P < .05).

Regulation of apical NHE3 trafficking by ouabain-induced activation of the basolateral Na+-K+-ATPase receptor complex.

The long-term effects of ouabain on transepithelial Na(+) transport involve transcriptional downregulation of apical Na(+)/H(+) exchanger isoform 3 (NHE3). The aim of this study was to determine whether ouabain could acutely regulate NHE3 via a posttranscriptional mechanism in LLC-PK1 cells. We observed that the basolateral, but not apical, application of ouabain for 1 h significantly reduced transepithelial Na(+) transport. This effect was not due to changes in the integrity of tight junctions or increases in the intracellular Na(+) concentration. Ouabain regulated the trafficking of NHE3 and subsequently inhibited its activity, a process independent of intracellular Na(+) concentration. Ouabain-induced NHE3 trafficking was abolished by either cholesterol depletion or Src inhibition. Moreover, ouabain increased the intracellular Ca(2+) concentration. Pretreatment of cells with the intracellular Ca(2+) chelator BAPTA-AM blocked ouabain-induced trafficking of NHE3. Also, blockade of Na(+)-K(+)-ATPase endocytosis by a phosphatidylinositol 3-kinase inhibitor was equally effective in attenuating ouabain-induced NHE3 trafficking. These data indicate that ouabain acutely stimulates NHE3 trafficking by activating the basolateral Na(+)-K(+)-ATPase signaling complex. Taken together with our previous observations, we propose that ouabain can simultaneously regulate basolateral Na(+)-K(+)-ATPase and apical NHE3, leading to inhibition of transepithelial Na(+) transport. This mechanism may be relevant to proximal tubular Na(+) handling during conditions associated with increases in circulating endogenous cardiotonic steroids.

Involvement of Na+/K+-ATPase in hydrogen peroxide-induced hypertrophy in cardiac myocytes.

We have shown that increased production of reactive oxygen species (ROS) was required for ouabain-induced hypertrophy in cultured cardiac myocytes. In the present study we assessed whether long-term exposure of myocytes to nontoxic ROS stress alone is sufficient to induce hypertrophy. A moderate amount of H2O2 was continuously generated in culture media by glucose oxidase. This resulted in a steady increase in intracellular ROS in cultured cardiac myocytes for at least 12 h. Such sustained, but not transient, increase in intracellular ROS at a level comparable to that induced by ouabain was sufficient to stimulate protein synthesis, increase cell size, and change the expression of several hypertrophic marker genes. Like ouabain, glucose oxidase increased intracellular Ca2+ and activated extracellular signal-regulated kinases 1 and 2 (ERK1/2). These effects of glucose oxidase were additive to ouabain-induced cellular changes. Furthermore, glucose oxidase stimulated endocytosis of the plasma membrane Na+/K+-ATPase, resulting in significant inhibition of sodium pump activity. While inhibition of ERK1/2 abolished glucose oxidase-induced increases in protein synthesis, chelating intracellular Ca2+ by BAPTA-AM showed no effect. These results, taken together with our prior observations, suggest that ROS may cross talk with Na+/K+-ATPase, leading to the activation of hypertrophic pathways in cardiac myocytes.

Functional characterization of Src-interacting Na/K-ATPase using RNA interference assay.

We have shown that the Na/K-ATPase and Src form a signaling receptor complex. Here we determined how alterations in the amount and properties of the Na/K-ATPase affect basal Src activity and ouabain-induced signal transduction. Several alpha1 subunit knockdown cell lines were generated by transfecting LLC-PK1 cells with a vector expressing alpha1-specific small interference RNA. Although the alpha1 knockdown resulted in significant decreases in Na/K-ATPase activity, it increased the basal Src activity and tyrosine phosphorylation of focal adhesion kinase, a Src effector. Concomitantly it also abolished ouabain-induced activation of Src and ERK1/2. When the knockdown cells were rescued by a rat alpha1, both Na/K-ATPase activity and the basal Src activity were restored. In addition, ouabain was able to stimulate Src and ERK1/2 in the rescued cells at a much higher concentration, consistent with the established differences in ouabain sensitivity between pig and rat alpha1. Finally both fluorescence resonance energy transfer analysis and co-immunoprecipitation assay indicated that the pumping-null rat alpha1 (D371E) mutant could also bind Src. Expression of this mutant restored the basal Src activity and focal adhesion kinase tyrosine phosphorylation. Taken together, the new findings suggest that LLC-PK1 cells contain a pool of Src-interacting Na/K-ATPase that not only regulates Src activity but also serves as a receptor for ouabain to activate protein kinases.