Functional alignment maximises advantages of robotic arm-assisted total knee arthroplasty with better patient-reported outcomes compared to mechanical alignment.

PURPOSE: Robotic arm-assisted total knee arthroplasty (RTKA) enables adjustment of implant position to achieve the surgeon's preferred alignment. However, the alignment concept that most effectively enhances patient satisfaction remains unclear. This study compares the clinical outcomes of patients who underwent functionally aligned RTKA (FA-RTKA), mechanically aligned conventional TKA (MA-CTKA) and mechanically aligned RTKA (MA-RTKA). METHODS: A prospectively collected database was retrospectively reviewed for patients who underwent primary TKA for knee osteoarthritis. One hundred and forty-seven knees were performed with MA-CTKA, followed by 72 consecutive knees performed with MA-RTKA, and subsequently, 70 consecutive knees performed with FA-RTKA were enrolled. After 1:1 propensity score matching of patient demographics, 70 knees were finally included in each group. The extent of additional soft tissue release during surgery was identified, and the Coronal Plane Alignment of the Knee classification was utilised to categorise the alignment. At the 1-year follow-up, patient-reported outcomes, including the pain Visual Analogue Scale, Knee Society Score, Western Ontario and McMaster Universities Arthritis Index and Forgotten Joint Score-12, were also compared among the groups. RESULTS: The FA-RTKA group showed significantly less additional soft tissue release than the MA-CTKA and MA-RTKA groups (15.7%, 38.6% and 35.7%, respectively; p = 0.006). Statistically significant differences in functional scores were observed in the postoperative 1-year clinical outcomes in favour of the FA-RTKA group, which had a significantly larger percentage of knees that maintained constitutional alignment and joint line obliquity than those of the other groups. CONCLUSIONS: Functionally aligned TKA showed superior 1-year postoperative patient-reported outcomes compared with those of conventional and robotic arm-assisted mechanically aligned TKA. Therefore, the advantage of RTKA is maximised when the implant positioning is based on functional alignment. The application of RTKA with mechanical alignment has been proven ineffective in improving the clinical outcomes of patients. LEVEL OF EVIDENCE: Level III.

Robotic-assisted medial unicompartmental knee arthroplasty restored prearthritic alignment and led to superior functional outcomes compared with conventional techniques.

PURPOSE: Robotic-assisted medial unicompartmental knee arthroplasty (UKA) can ensure precise preoperative planning, minimise soft tissue damage and restore native coronal alignment. However, few studies have investigated how these advantages translate into differences in early postoperative outcomes. This study aimed to compare differences in early outcomes between conventional UKA (C-UKA) and robotic-assisted UKA (R-UKA). METHODS: This retrospective study investigated two groups of patients who underwent medial UKA: C-UKA group (n = 35) and R-UKA group (n = 35). We assessed (1) serum indicators (hemoglobin, creatine kinase and C-reactive protein) and pain visual analogue scale (VAS) at postoperative days (PODs) 1, 2, 4 and 6; (2) radiologic parameters including joint line height change and arithmetic and mechanical hip-knee-ankle angle (aHKA and mHKA); (3) patient-reported outcomes including Knee Society Scores, Western Ontario and Mcmaster Universities Arthritis Index (WOMAC) and Forgotten Joint Score-12 (FJS-12) at 1-year follow-up. RESULTS: Despite similar serum indicator results, pain VAS was lower in the R-UKA group than in the C-UKA group at PODs 2 (2.5 ± 1.3 vs. 3.6 ± 1.2, p = 0.02), 4 (2.4 ± 0.9 vs. 3.3 ± 1.0, p = 0.03) and 6 (1.9 ± 1.1 vs. 3.1 ± 1.1, p < 0.01). The joint line height change was significantly lower in the R-UKA group than in the C-UKA group (0.9 mm ± 0.6 mm vs. 2.0 mm ± 1.3 mm, p = 0.02). The equivalence test for preoperative aHKA and postoperative mHKA revealed equivalence in only the R-UKA group (p < 0.01). The R-UKA group showed better WOMAC and FJS-12 compared to C-UKA group at 1-year follow-up. CONCLUSION: R-UKA led to lower pain VAS in the early postoperative period compared with C-UKA. Additionally, R-UKA effectively restored the joint line and prearthritic lower limb alignment, resulting in superior functional outcomes at 1-year follow-up compared with C-UKA. LEVEL OF EVIDENCE: Level III.

Comprehensiveness of cardiac rehabilitation program in Korea: a nation-wide survey result.

BACKGROUND: Cardiac rehabilitation (CR) is an essential component in secondary prevention of cardiovascular diseases. Current guidelines recommend that the program should be comprehensive including multidisciplinary behavioral intervention, not only exercise training. While the utilization of CR is gradually increasing, the comprehensiveness of the program has not been systemically evaluated in Korea. METHODS: During the year 2020, nation-wide survey was done to evaluate the current status of CR in Korea. Survey was done by web-based structured questionnaire. Survey was requested to 164 hospitals performing percutaneous coronary intervention. RESULTS: Among 164 hospitals, 47 (28.7%) hospitals had CR programs. In hospitals with CR, multidisciplinary intervention other than exercise-based program was provided only partially: nutritional counseling (63%), vocational counseling for return to work (39%), stress management (31%), psychological evaluation (18%). Personnel for CR was commonly not dedicated to the program or even absent: (percentage of dedicated, concurrent with other work, absent) physical therapist (59, 41, 0%), nurse (31, 69, 0%), dietician (6, 65, 29%), clinical psychologist (0, 37, 63%). CONCLUSION: Comprehensiveness of CR in Korea is suboptimal and human resource for it is poorly disposed. More awareness of current status by both clinicians and health policy makers is needed and insurance reimbursement for educational program should be improved.

Learning curve of robot-assisted total knee arthroplasty and its effects on implant position in asian patients: a prospective study.

BACKGROUND: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients. METHODS: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups. RESULTS: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P. CONCLUSION: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve.

Preoperative patellar bone marrow lesions with full thickness cartilage defects correlate with residual anterior knee pain in total knee arthroplasty without patellar resurfacing.

PURPOSE: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA. METHODS: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups. RESULTS: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups. CONCLUSIONS: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA. LEVEL OF EVIDENCE: III.

Cut-Off Value of Voluntary Peak Cough Flow in Patients with Parkinson's Disease and Its Association with Severe Dysphagia: A Retrospective Pilot Study.

Background and Objectives. Swallowing and coughing reflexes are both closely associated with airway protection. Peak cough flow (PCF) is associated with dysphagia in several neurogenic diseases. In this study, we aimed to analyze the relationship between PCF and aspiration in Parkinson's disease (PD) and determine the cut-off value of PCF. Materials and Methods. We retrospectively analyzed the records of patients with PD who underwent a videofluoroscopic swallowing study and checked for PCF. A total of 219 patients were divided into an aspiration group (n = 125) and a non-aspiration group (n = 94). Results. Significantly lower PCF values were observed in the aspiration group compared to the non-aspiration group (132.63 ± 83.62 vs. 181.38 ± 103.92 L/min, p < 0.001). Receiver operating characteristic curve analysis revealed that a PCF cut-off value of 153 L/min (area under the receiver operating characteristic curve, 0.648; sensitivity, 73.06%; specificity, 51.06%) was associated with aspiration in PD. Additionally, a univariate analysis showed that the male sex, lower body mass indexes, higher Hoehn and Yahr scales, and PCF values of ≤153 L/min indicated an increased risk of aspiration. Conclusions. Through a multivariate analysis, we demonstrated that a PCF value ≤153 L/min was associated with an increased risk of aspiration (odds ratio 3.648; 1.797-7.407), highlighting that a low PCF is a risk factor for aspiration in patients with PD.

The Association of Intravenous Iron Administered the Day before Total Knee Arthroplasty with Postoperative Anemia and Functional Recovery.

Background and Objectives: Total knee arthroplasty (TKA) involves blood loss, increasing the risk of postoperative anemia and delayed functional recovery. Intravenous (IV) iron supplementation limits postoperative anemia; however, the effectiveness of IV iron, administered one day before TKA, on postoperative anemia and functional recovery has scarcely been studied. Materials and Methods: We conducted a retrospective cohort study with propensity score matching using two consecutive groups of patients who underwent TKA using tranexamic acid: the iron group received 500 mg ferric derisomaltose intravenously one day before surgery (n = 46); the non-iron group did not (n = 46). Hemoglobin (Hb) level was determined at postoperative days (PODs) 2, 4, 6, 14, and 30. Ferritin, transferrin saturation (TSAT), and functional iron deficiency anemia (IDA) rate were measured at PODs 2, 4, 6, and 14. Length of hospital stay and transfusion rate were also evaluated. Results: The iron group had higher Hb levels at PODs 6, 14, and 30 and higher ferritin and TSAT at PODs 2, 4, 6, and 14. The functional IDA rate was significantly higher in the non-iron group at PODs 2, 4, 6, and 14. Length of hospital stay was significantly shorter in the iron group; however, the rate of transfusion did not differ between the two groups. Conclusions: IV iron administered one day before TKA was associated with postoperative anemia recovery and length of hospital stay; however, it did not lower the postoperative transfusion rate.

A survey of the perceptions of barriers to and facilitators of cardiac rehabilitation in healthcare providers and policy stakeholders.

BACKGROUND: Cardiac rehabilitation (CR) is a prognostic management strategy to help patients with CVD achieve a good quality of life and lower the rates of recurrence, readmission, and premature death from disease. Globally, cardiac rehabilitation is poorly established in hospitals and communities. Hence, this study aimed to investigate the discrepancies in the perceptions of the need for CR programs and relevant health policies between directors of hospitals and health policy personnel in South Korea to shed light on the status and to establish practically superior and effective strategies to promote CR in South Korea. METHODS: We sent a questionnaire to 592 public health policy managers and directors of selected hospitals, 132 of whom returned a completed questionnaire (response rate: 22.3%). The participants were categorized into five types of organizations depending on their practice of PCI (Percutaneous Coronary Intervention), establishment of cardiac rehabilitation, director of hospital, and government's policy makers. Differences in the opinions between directors of hospitals that perform/do not perform PCI, directors of hospitals with/without cardiac rehabilitation, and between hospital directors and health policy makers were analyzed. RESULTS: Responses about targeting diseases for cardiac rehabilitation, patients' roles in cardiac rehabilitation, hospitals' roles in cardiac rehabilitation, and governmental health policies' roles in cardiac rehabilitation were more positive among hospitals that perform PCI than those that do not. Responses to questions about the effectiveness of cardiac rehabilitation and hospitals' roles in cardiac rehabilitation tended to be more positive in hospitals with cardiac rehabilitation than in those without. Hospital directors responded more positively to questions about targeting diseases for cardiac rehabilitation and governmental health policies' roles in cardiac rehabilitation than policy makers, and both hospitals and public organizations provided negative responses to the question about patients' roles in cardiac rehabilitation. Responses to questions about targeting diseases for cardiac rehabilitation, patients' roles in cardiac rehabilitation, and governmental health policies' roles in cardiac rehabilitation were more positive in hospitals that perform PCI than those that do not and public organizations. CONCLUSIONS: Hospitals must ensure timely referral, provide education, and promote the need for cardiac rehabilitation. In addition, governmental socioeconomic support is needed in a varity of aspects.

Evaluation of Current Resources Available for Community-Based Cardiac Rehabilitation in Korea: A Nationwide Survey Study.

BACKGROUND: In Korea, the actual distribution of cardiac rehabilitation (CR) to the clinical field is insufficient due to the many barriers for cardiovascular patients to participate in CR. Community-based CR is a useful alternative to overcome these obstacles. Through a nationwide survey, we investigated the possibility of regional medical and public health management institutes which can be in charge of community-based CR in Korea. METHODS: The questionnaires on recognition of CR and current available resources in health-related institutions were developed with reference to the CR evaluation tools of York University and the International Council of Cardiovascular Prevention and Rehabilitation. The questionnaires were sent to regional public and private medical institutions and public health management institutions. RESULTS: In total, 2,267 questionnaires were sent to 1,186 institutions. There were 241 and 242 responses from 173 and 179 regional private and public medical institutions, respectively. And a total of 244 responses were gathered from 180 public health management institutions. Although many institutions were equipped with the necessary facilities for exercise training, there were few patient-monitoring systems during exercise. Most institutions were aware of the need for CR, but were burdened with the cost of establishing personnel and facilities to operate CR. CONCLUSION: Most regional medical, and public health management institutions in Korea are unprepared for the implementation of community-based CR programs. To encourage the utilization of such, there should be efforts to establish a national consensus.

Gender differences and dose proportionality in the toxicokinetics of udenafil and its active metabolite following oral administration in rodents.

Udenafil is a long-acting oral phosphodiesterase type 5 inhibitor used to treat erectile dysfunction which may also have beneficial effects on cardiovascular diseases. Udenafil is mainly biotransformed to the active metabolite N-dealkylated udenafil via cytochrome P450 3A. The aim of this study was to investigate the gender differences and dose proportionality of the toxicokinetics of udenafil and its metabolite N-dealkylated udenafil in rodents. Udenafil was administered orally by gavage to male and female B6C3F1/N mice (100, 240, 350, and 500 mg/kg) and F344 rats (60, 120, and 240 mg/kg). Plasma concentrations of udenafil and N-dealkylated udenafil were simultaneous measured via liquid chromatography-tandem mass spectrometry. Female mice showed higher systemic exposure to udenafil than male mice, whereas female rats showed lower systemic exposure to udenafil than male rats after repeated administration at high dose. Systemic exposure to the metabolite, N-dealkylated udenafil, was lower in female than male mice and rats. A dose proportionality assessment by power model revealed a lack of dose proportionality in systemic exposure (Cmax, AUC24h and AUCinf) after administration of 100-500 mg/kg of udenafil in mice and 60-240 mg/kg in rats. This study thus demonstrates gender and species differences with regard to the toxicokinetic profiles of udenafil and its active metabolite N-dealkylated udenafil after oral administration of udenafil to mice and rats of both sexes. Our findings suggest the possibility of gender differences in the toxicokinetics of udenafil in humans and suggests that further study is needed in this cohort.

Finger drop sign as a new variant of acute motor axonal neuropathy.

We propose the finger drop sign as a new clinical variant of acute motor axonal neuropathy (AMAN) defined by immunological and radiological evidence. We identified eight consecutive patients who had AMAN. All of them developed prominent involvement of the finger extensors. We performed magnetic resonance imaging (MRI) of the extremity muscles and serological assays for antiganglioside antibodies and Campylobacter jejuni. Patients with AMAN showed characteristic and a markedly sustained weakness of the finger extensors with a distinctive pattern of the finger drop sign. Limb MRI revealed unevenly distributed abnormal signals in the muscles mainly innervated by the posterior interosseous nerve. All tested patients showed positivity for immunoglobulin G antibody against ganglioside complex of GM1 and phosphatidic acid. A pathophysiological understanding of this unique syndrome can provide further insight into antiganglioside-antibody-mediated axonal injury in Guillain-Barré syndrome.

Simultaneous Quantification of 3'- and 6'-Sialyllactose in Rat Plasma Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application to a Pharmacokinetic Study.

Sialyllactose (SL), an acidic oligosaccharide, has immune-protective effects against pathogens and helps with the development of the immune system and intestinal microorganisms. To elucidate the pharmacokinetic characterization after oral administration to rats, the simultaneous quantification method for 3'-SL and 6'-SL in rat plasma was validated, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in an electrospray ionization (ESI) mode. Several types of columns [C18, amide, and hydrophilic interaction liquid chromatography (HILIC) phase] were used to separate the peaks of 3'-SL and 6'-SL, which improved chromatographic selectivity. Ultimately, the HILIC phase column had a good peak shape and quick resolution, with a mobile phase comprising ammonium acetate buffer and acetonitrile obtained by gradient elution. In addition, the simultaneous quantification of 3'-SL and 6'-SL in rat plasma samples were adequately applied to pharmacokinetic study.

Saline Load Test and Quilting Sutures to Treat Intractable Lateral Malleolar Bursitis.

The purpose of this study was to evaluate the clinical outcomes of patients with intractable lateral malleolar bursitis who were treated using the intraoperative saline load test to find communication between the bursal sac and the ankle joint and the quilting sutures after bursectomy to reduce the dead space. We reviewed a total of 28 patients who had been treated with quilting sutures after bursectomy between April 2014 and June 2017. When there was capsular opening detected with the saline load test, it was closed with sutures or augmented with periosteum. On the final follow-up office visit, the lateral malleolus was examined for the recurrence of bursitis. Patient medical records were reviewed for postoperative wound dehiscence, skin necrosis, infections, and nerve symptoms. The saline load test was positive in 11 (42%) cases. The mean foot function index improved from 25.94 ± 20.46 to 11.73 ± 5.27 (p = .003). Fourteen (54%) patients were very satisfied with the results, 9 (35%) were satisfied, 2 (8%) rated their satisfaction as fair, and 1 (4%) was dissatisfied. No cases required skin graft or flap surgery. Intractable lateral malleolar bursitis was successfully treated using the saline load test and quilting sutures after bursectomy. Closure of the capsular opening prevented fluid drainage around the wound. Quilting sutures after bursectomy reduced dead space underneath the wound to prevent fluid accumulation and promoted healing of the skin on the underlying soft tissue.

Development and Validation of a Bioanalytical Method for 3'- and 6'-Sialyllactose in Minipig Liver and Kidney Using Liquid Chromatography-Tandem Mass Spectrometry and Its Application to Analysis of Tissue Distribution.

Breast milk contains human milk oligosaccharides (HMOs), including sialyllactose (SL). SL is composed of sialic acid and lactose, and is divided into 3'-SL and 6'-SL according to the binding position. SL has immunoprotective effects against bacteria and viruses, and acts as a probiotic in the gastrointestinal tract. In this study, we developed a bioanalytical method for simultaneous analysis of 3'-SL and 6'-SL in liver and kidney tissues of Yucatan minipigs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) under conditions optimized in our previous study. LC-MS/MS was performed using a hydrophilic interaction liquid chromatography (HILIC) column (50 mm × 2.1 mm, 3 µm) with a mobile phase consisting of 10 mM ammonium acetate in water (pH 4.5) and acetonitrile with gradient elution at a flow rate of 0.3 mL/min. A surrogate matrix method using water was applied for analysis of endogenous SL. The developed method was validated with regard to selectivity, linearity, precision, accuracy, the matrix effect, recovery, parallelism, dilution integrity, carryover, and stability according to the US Food and Drug Administration guidelines. We performed a tissue distribution study of minipigs, and analyzed liver and kidney tissues using the developed method to determine the tissue distribution of 3'-SL and 6'-SL. The tissue concentrations of 3'-SL and 6'-SL were readily measurable, suggesting that the method would be useful for evaluating the tissue distributions of these compounds in minipigs.

Development and Validation of Analytical Method for SH-1242 in the Rat and Mouse Plasma by Liquid Chromatography/Tandem Mass Spectrometry.

SH-1242, a novel inhibitor of heat shock protein 90 (HSP90), is a synthetic analog of deguelin: It was previously reported that the treatment of SH-1242 led to a strong suppression of hypoxia-mediated retinal neovascularization and vascular leakage in diabetic retinas by inhibiting the hypoxia-induced upregulation of expression in hypoxia-inducible factor 1α (HIF-1ɑ) and vascular endothelial growth factor (VEGF). In this study, an analytical method for the quantification of SH-1242 in biological samples from rats and mice was developed/validated for application in pharmacokinetic studies. SH-1242 and deguelin, an internal standard of the assay, in plasma samples from the rodents were extracted with methanol containing 0.1% formic acid and analyzed at m/z transition values of 368.9→151.0 and 395.0→213.0, respectively. The method was validated in terms of accuracy, precision, dilution, matrix effects, recovery, and stability and shown to comply with validation guidelines when it was used in the concentration ranges of 1-1000 ng/mL for rat plasma and of 2-1000 ng/mL for mouse plasma. SH-1242 levels in plasma samples were readily determined using the developed method for up to 480 min after the intravenous administration of 0.1 mg/kg SH-1242 to rats and for up to 120 min to mice. These findings suggested that the current method was practical and reliable for pharmacokinetic studies on SH-1242 in preclinical animal species.

Development and Operation of a Video Teleconsultation System Using Integrated Medical Equipment Gateway: a National Project for Workers in Underserved Areas.

Worker health centers and health zones provide occupational healthcare services to workers in underserved areas of industrial health. Health zones cannot counsel workers on occupational disease prevention; worker health center personnel have to provide such services through in-person visits. Video teleconsultation can increase the accessibility of high-quality services to workers who visit health zones and improve professional personnel's efficiency. This study aimed to develop a system and an infrastructure that could facilitate video teleconsultation services between worker health centers and health zones, and analyze the services' operation status. A video teleconsultation process based on the role of local and remote institutions was designed. Based on the designed services, a web system supporting teleconsultation and an integrated gateway guaranteeing the interface with medical equipment in the web environment was developed. After analyzing the working environment, an infrastructure consisting of networks, video equipment, medical equipment, and servers necessary for teleconsultation was designed. Statistical results from the developed system and a satisfaction survey conducted by the Korea Occupational Safety and Health Agency were used to analyze the video teleconsultation services' operation status. A system, gateway, and hardware infrastructure within 21 worker health centers and 21 health zones has been operating this service since January 1, 2018. Over two years, the total number of teleconsultation service users was 4979, and the total number of questionnaire respondents was 1270. The total number of service activities was 6388 and total satisfaction was rated as 4.58 (± 0.59) out of 5. In this study, video teleconsultation services were evaluated as being very satisfactory. In particular, service accessibility and local medical personnel service were rated highly, demonstrating that the developed system and infrastructure were well designed according to the goals of the project.

Predictive value of sarcopenia and visceral obesity for postoperative pancreatic fistula after pancreaticoduodenectomy analyzed on clinically acquired CT and MRI.

OBJECTIVE: To evaluate predictive values of sarcopenia and visceral obesity measured from preoperative CT/MRIs for postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy in patients with periampullary malignancies. METHODS: From the prospectively constructed surgical registry, we included adult patients treated with pancreaticoduodenectomy. Based on CT/MRIs, body morphometric analysis was performed to evaluate the visceral obesity and sarcopenia, based on the areas of visceral fat and skeletal muscle measured at the L3 vertebrae level. We retrieved various perioperative factors from registry. As outcomes of postoperative complications, we evaluated POPF and major complications based on the Clavien-Dindo classification. Multivariate logistic regression analyses were performed. RESULTS: From a total of 284 patients (163 males, 121 females) who met the inclusion/exclusion criteria, POPF, major complications, and 60-day mortality occurred in 52 (18.3%), 34 (12.0%), and 6 (2.1%), respectively. Sarcopenia and visceral obesity were noted in 123 (75.5%) and 66 (40.5%) of men and 68 (56.2%) and 53 (43.8%) of women, respectively. Combination of sarcopenia and obesity (sarcopenic obesity) was noted in 31.9% (52/163) of men and in 26.4% (32/121) of women. In multivariate logistic regression analyses, sarcopenic obesity was the only independent predictor for POPF (OR 2.65, 95% CI 1.43-4.93), and the vascular resection during pancreaticoduodenectomy was the only independent predictor for severe complications (OR 3.75, 95% CI 1.61-8.70). CONCLUSION: Sarcopenic obesity might be highly predictive for POPF. Body morphometric analysis in preoperative CT/MRI combined with assessment of perioperative clinical features may help to identify high-risk patients and determine perioperative management strategies. KEY POINTS: • Sarcopenic obesity might be predictive for postoperative pancreatic fistula after pancreaticoduodenectomy. • The vascular resection during pancreaticoduodenectomy might be predictive of major complications. • Body morphometric analysis might be helpful for identifying high-risk patients.

Specific Inhibition of the Distribution of Lobeglitazone to the Liver by Atorvastatin in Rats: Evidence for a Rat Organic Anion Transporting Polypeptide 1B2-Mediated Interaction in Hepatic Transport.

Cytochrome P450 enzymes and human organic anion transporting polypeptide (OATP) 1B1 are reported to be involved in the pharmacokinetics of lobeglitazone (LB), a new peroxisome proliferator-activated receptor γ agonist. Atorvastatin (ATV), a substrate for CYP3A and human OATP1B1, is likely to be coadministered with LB in patients with the metabolic syndrome. We report herein on a study of potential interactions between LB and ATV in rats. When LB was administered intravenously with ATV, the systemic clearance and volume of distribution at steady state for LB remained unchanged (2.67 ± 0.63 ml/min per kg and 289 ± 20 ml/kg, respectively), compared with that of LB without ATV (2.34 ± 0.37 ml/min per kg and 271 ± 20 ml/kg, respectively). Although the tissue-to-plasma partition coefficient (Kp) of LB was not affected by ATV in most major tissues, the liver Kp for LB was decreased by ATV coadministration. Steady-state liver Kp values for three levels of LB were significantly decreased as a result of ATV coadministration. LB uptake was inhibited by ATV in rat OATP1B2-overexpressing Madin-Darby canine kidney cells and in isolated rat hepatocytes in vitro. After incorporating the kinetic parameters for the in vitro studies into a physiologically based pharmacokinetics model, the characteristics of LB distribution to the liver were consistent with the findings of the in vivo study. It thus appears that the distribution of LB to the liver is mediated by the hepatic uptake of transporters such as rat OATP1B2, and carrier-mediated transport is involved in the liver-specific drug-drug interaction between LB and ATV in vivo.