Association between hospital acquired disability and post-discharge mortality in patients after living donor liver transplantation.

BACKGROUND: Hospital-acquired disability (HAD) in patients who undergo living donor liver transplantation (LDLT) is expected to worsen physical functions due to inactivity during hospitalization. The aim of this study was to explore whether a decline in activities of daily living from hospital admission to discharge is associated with prognosis in LDLT patients, who once discharged from a hospital. METHODS: We retrospectively examined the relationship between HAD and prognosis in 135 patients who underwent LDLT from June 2008 to June 2018, and discharged from hospital once. HAD was defined as a decline of over 5 points in the Barthel Index as an activity of daily living assessment. Additionally, LDLT patients were classified into four groups: low or high skeletal muscle index (SMI) and HAD or non-HAD. Univariate and multivariate Cox proportional hazard models were used to evaluate the association between HAD and survival. RESULTS: HAD was identified in 47 LDLT patients (34.8%). The HAD group had a significantly higher all-cause mortality than the non-HAD group (log-rank: p < 0.001), and in the HAD/low SMI group, all-cause mortality was highest between the groups (log-rank: p < 0.001). In multivariable analysis, HAD was an independent risk factor for all-cause mortality (hazard ratio [HR]: 16.54; P < 0.001) and HAD/low SMI group (HR: 16.82; P = 0.002). CONCLUSION: HAD was identified as an independent risk factor for all-cause mortality suggesting that it could be a key component in determining prognosis after LDLT. Future larger-scale studies are needed to consider the overall new strategy of perioperative rehabilitation, including enhancement of preoperative physiotherapy programs to improve physical function.

Predictors of sedation period for critical illness patients focusing on early rehabilitation on the bed.

There are various interventions of rehabilitation on the bed, but these are time-consuming and cannot be performed for all patients. The purpose of this study was to identify the patients who require early mobilization based on the level of sedation. We retrospectively evaluated the data of patients who underwent physical therapy, ICU admission of > 48 h, and were discharged alive. Sedation was defined as using sedative drugs and a Richmond Agitation-Sedation Scale score of < - 2. Multiple regression analysis was performed using sedation period as the objective variable, and receiver operating characteristic (ROC) curve and Spearman's rank correlation coefficient were performed. Of 462 patients admitted to the ICU, the data of 138 patients were analyzed. The Sequential Organ Failure Assessment (SOFA) score and non-surgery and emergency surgery cases were extracted as significant factors. The ROC curve with a positive sedation period of more than 3 days revealed the SOFA cutoff score was 10. A significant positive correlation was found between sedation period and the initial day on early mobilization. High SOFA scores, non-surgery and emergency surgery cases may be indicators of early mobilization on the bed in the ICU.

Role of Early Mobilization on the Clinical Course of Patients who Underwent Pancreaticoduodenectomy: A Retrospective Cohort Study.

The length of hospital stay is an important outcome measure in patients who have undergone pancreaticoduodenectomy. Although postoperative complications are known to adversely affect the length of hospital stay (LOS), the influence of early mobilization on LOS has not been clarified yet. This study aimed to examine the impact of the initial ambulation day, which is one of the components of early mobilization, on LOS after pancreaticoduodenectomy. We retrospectively enrolled patients who underwent pancreaticoduodenectomy between January 2013 and December 2017. Postoperative complications were evaluated using the Clavien-Dindo classification (CDC) system. Patients were divided into two groups based on the median LOS (early and late-discharge groups) and compared to determine their characteristics. Multivariate logistic regression analysis was performed with LOS as the dependent variable. Patients in the late-discharge group were significantly older, had an initial ambulation delay, and had higher rates of advanced disease stages and a CDC grade ≥ IIIa than those in the early discharge group. In the multivariate logistic regression analysis, CDC grade ≥ IIIa, initial ambulation day, and age were found to be significant independent factors associated with LOS. Our results demonstrated that not only postoperative complications, but also the initial ambulation day, could affect LOS after pancreaticoduodenectomy, emphasizing the importance of early ambulation for patients who undergo this surgery.

Factors Influencing Functional Exercise Capacity After Lung Resection for Non-Small Cell Lung Cancer.

Purpose: We investigated, in patients who underwent lung resection for non-small cell lung cancer (NSCLC), the magnitude of early limitation in functional exercise capacity and the associations with pre- and postoperative factors. Methods: Consecutive patients with preoperative clinical stage I to IIIA NSCLC who underwent lung resection were prospectively enrolled. We measured functional exercise capacity (6-minute walk distance [6MWD]) and skeletal muscle strength (handgrip [HF] and quadriceps force [QF]) within 2 days prior to surgery and on day 7 postoperatively. Results: Two hundred eighteen participants were recruited (median age 69 years) of whom 49 developed postoperative complications (POCs). 6MWD was markedly decreased (514 m vs 469 m, P < .001); HF and QF were slightly decreased following surgery. Multiple linear regression showed that preoperative vital capacity (P < .01), QF (P < .05), the duration of chest tube drainage (P < .001), and presence of POCs (P < .05) were significant predictors. However, intraoperative factors were not significantly associated with the decline in 6MWD. Conclusions: These results suggest that patients with preoperative impairments in pulmonary function and muscle strength, and those who require prolonged chest tube drainage or develop POCs are likely to have impaired exercise capacity. Therefore, individual assessment and follow-up of patients with such factors is indicated.

Effects of quadriceps muscle neuromuscular electrical stimulation in living donor liver transplant recipients: phase-II single-blinded randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of neuromuscular electrical stimulation on quadriceps muscle strength and thickness in liver transplantation patients. DESIGN: Phase-II, randomized, parallel-group, allocation-concealed, assessor-blinded, single-center controlled trial. SETTING: Inpatient rehabilitation sector. SUBJECTS: Patients following living donor liver transplantation. INTERVENTIONS: The quadriceps muscle stimulation and the control groups received bilateral muscle electrical stimulation on the quadriceps and tibialis anterior muscles, respectively. Neuromuscular electrical stimulation sessions in both groups were conducted for 30 minutes per session, once per day for five weekdays over four weeks by a physical therapist. MAIN MEASURES: Quadriceps muscle strength and quadriceps muscle thickness. RESULTS: Neuromuscular electrical stimulation was applied to the quadriceps muscles group ( n = 23) or the tibialis anterior muscle in the control group ( n = 22). The decrease in quadriceps muscle thickness differed significantly between both groups on postoperative day 30 (median -3 vs -8, P < 0.01). The changes in predicted quadriceps strength and 6 minutes walking distance were not significantly different between groups (quadriceps strength median -12% vs -5%, P = 0.40; 6 minutes walking distance median -18 vs -21 m, P = 0.74). CONCLUSION: Neuromuscular electrical stimulation of the quadriceps muscle for liver transplantation recipients was able to maintain the quadriceps muscle thickness after surgery. Future larger scale studies are needed to consider the effectiveness of neuromuscular electrical stimulation and how to incorporate this intervention in the overall strategy of the physical therapy program.

Effect of early mobilization on postoperative pulmonary complications in patients undergoing video-assisted thoracoscopic surgery on the esophagus.

BACKGROUND: Esophagectomy performed via thoracotomy is associated with a high rate of postoperative pulmonary complications. Video-assisted thoracoscopic surgery at the esophagus (VATS-E) can reduce the rate of postoperative pulmonary complications. VATS-E is being increasingly implemented owing to its benefits. This procedure makes early patient mobilization possible, because there is minimal thoracic wall invasion, and thus, less postoperative pain. This study aimed to identify the efficacy of early mobilization in patients undergoing VATS-E. METHODS: We retrospectively reviewed the patients who underwent VATS-E between November 2008 and October 2016. All the patients underwent preoperative physiotherapy and postoperative early mobilization for standard perioperative management. We examined the relation between early mobilization and the factors affecting postoperative pulmonary complications and the duration of physiotherapy with regard to the surgical outcome of VATS-E. RESULTS: A total of 118 patients who underwent VATS-E were assessed. The incidence of postoperative pulmonary atelectasis decreased with early mobilization, and earlier mobilization was associated with a better decrease (P < 0.001). Multiple logistic regression analysis identified the percentage of volume capacity [odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99] and initial walking (OR 1.82; 95% CI 1.40-2.48) as independent risk factors for postoperative pulmonary atelectasis. In addition, the presence or absence of atelectasis was found to reduce the necessary period of physiotherapy (P < 0.001). CONCLUSION: Our results indicated that early mobilization reduces the incidence of postoperative pulmonary atelectasis, which may also contribute to early recovery in patients who undergo VATS-E.

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery.

BACKGROUND: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. METHODS: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. RESULTS: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. CONCLUSIONS: These results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized. TRIAL REGISTRATION: University hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632 . (Registered on 1st October, 2008).

[Current Status of Perioperative Rehabilitation in Patients who Undergo Esophagectomy for Cancer].

The esophagectomy for esophageal cancer is major surgery and has the highest rate of postoperative pulmonary complications. Respiratory physiotherapy in patients undergoing esophagectomy has been applied to improve oxygenation and airway secretion clearance. Recently, the utility and effectiveness of enhanced recovery after surgery for gastroenterological surgery have been reported in Japan, and patients should be encouraged to participate in early mobilization. Perioperative rehabilitation which includes early mobilization reduces postoperative complications and improves fast-track recovery after esophagectomy. These interventions play important role in postoperative care.

Protoaculeine B, a putative N-terminal residue for the novel peptide toxin aculeines.

A new polyamine-modified indole derivative protoaculeine B (1) was isolated from Okinawan marine sponge Axinyssa aculeata. The structure of 1 was assigned on the basis of spectral data along with chemical transformations. Because the structure of 1 greatly inferred the N-terminal amino acid for highly modified peptide toxin aculeines, the probable structure for aculeine B was proposed on the basis of high-resolution mass spectral analysis.

Damnacanthal, an effective inhibitor of LIM-kinase, inhibits cell migration and invasion.

LIM-kinases (LIMKs) play crucial roles in various cell activities, including migration, division, and morphogenesis, by phosphorylating and inactivating cofilin. Using a bimolecular fluorescence complementation assay to detect the actin-cofilin interaction, we screened LIMK1 inhibitors and identified two effective inhibitors, damnacanthal (Dam) and MO-26 (a pyrazolopyrimidine derivative). These compounds have already been shown to inhibit Lck, a Src family tyrosine kinase. However, in vitro kinase assays revealed that Dam inhibited LIMK1 more effectively than Lck. Dam suppressed LIMK1-induced cofilin phosphorylation and deceleration of actin retrograde flow in lamellipodia in N1E-115 cells. Dam impaired CXCL12-induced chemotactic migration of Jurkat T lymphocytes and Jurkat-derived, Lck-deficient JCaM1.6 cells and also inhibited serum-induced migration and invasion of MDA-MB-231 breast carcinoma cells. These results suggest that Dam has the potential to suppress cell migration and invasion primarily through the inhibition of LIMK kinase activity. Topical application of Dam also suppressed hapten-induced migration of epidermal Langerhans cells in mouse ears. Dam provides a useful tool for investigating cellular and physiological functions of LIMKs and holds promise for the development of agents against LIMK-related diseases. The bimolecular fluorescence complementation assay system used in this study will provide a useful method to screen for inhibitors of various protein kinases.

Endotoxic and immunobiological activities of a chemically synthesized lipid A of Helicobacter pylori strain 206-1.

A synthetic lipid A of Helicobacter pylori strain 206-1 (compound HP206-1), which is similar to its natural lipid A, exhibited no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). Furthermore, compound HP206-1 as well as its natural lipid A demonstrated no or very low mitogenic responses in murine spleen cell. On the other hand, compound HP206-1 showed a weaker but significant production of interleukin-8 in a gastric cancer cell line, MKN-1, in comparison with compound 506. Furthermore, compound HP206-1 exhibited induction of tumor necrosis factor-alpha production in human peripheral blood mononuclear cells and the cytokine production was clearly inhibited by mouse anti-human Toll-like receptor (TLR) 4 monoclonal antibody HTA125. Our findings indicate that the chemically synthesized lipid A, mimicking the natural lipid A portion of lipopolysaccharide from H. pylori strain 206-1, has a low endotoxic potency and immunobiological activities, and is recognized by TLR4.

Structural basis for endotoxic and antagonistic activities: investigation with novel synthetic lipid A analogs.

Our early work using homogeneous synthetic preparations demonstrated the presence of a lipid A analog which antagonizes endotoxic activities of LPS and lipid A. The first example was a tetraacylated biosynthetic precursor, now known as precursor Ia or lipid IVa, that contains four 3-hydroxytetradecanoyl moieties linked to the bisphosphorylated disaccharide backbone common to the endotoxic hexa-acyl Escherichia coli lipid A. Various compounds with both endotoxic and antagonistic activities have subsequently been reported from either natural or synthetic sources, but little is known about the factors determining the type of the activities of the respective compounds. To approach this issue, we have synthesized a series of lipid A analogs with various numbers and chain lengths of acyl groups on the backbone. Some were prepared by the aid of a novel affinity separation procedure. The phosphate moieties were also synthetically replaced. Biological tests showed that at least three acyl groups are required for antagonistic activity but one or even both of the phosphates can be replaced with other acidic moieties without losing the activity. The effect of Kdo residues linked to lipid A is also briefly discussed. Molecular dynamics calculations reasonably explain possible conformations required for the biological activity.