Applications of In Vivo Functional Testing of the Rat Tibialis Anterior for Evaluating Tissue Engineered Skeletal Muscle Repair

We describe an in vivo protocol to measure dorsiflexion of the foot following stimulation of the peroneal nerve and contraction of the anterior crural compartment of the rat hindlimb. Such measurements are an indispensable translational tool for evaluating skeletal muscle pathology and tissue engineering approaches to muscle repair and regeneration.

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Lamivudine switch therapy in chronic hepatitis B patients achieving undetectable hepatitis B virus DNA after 3 years of entecavir therapy: A prospective, open-label, multicenter study

Publication date: Available online 7 October 2016
Source:The Kaohsiung Journal of Medical Sciences
Author(s): Ming-Lun Yeh, Ching-I. Huang, Ming-Yen Hsieh, Chung-Feng Huang, Meng-Hsuan Hsieh, Jee-Fu Huang, Chia-Yen Dai, Zu-Yau Lin, Shinn-Chern Chen, Ming-Lung Yu, Wan-Long Chuang
The subsequent maintenance therapy in chronic hepatitis B (CHB) patients after long-term viral replication suppression is still uncertain. We aim to evaluate the efficacy of lamivudine (LAM) maintenance therapy in CHB patients achieving undetectable hepatitis B virus (HBV) DNA after 3 years of entecavir (ETV) therapy. Consecutive CHB patients who received at least 3 years of ETV and achieved HBV DNA negativity were allocated either LAM switch therapy or stopped ETV therapy in a prospective, open-label study. Another group of sex- and age-matched patients with continuous ETV therapy for at least 4 years served as historical control group. The primary outcome measurement of the study was relapse of HBV DNA (defined as serum HBV DNA level ≥ 2000 IU/mL). A total of 74 patients, including 42 of LAM switch and 32 of the nonswitch group, were enrolled. There were no significant differences in demographics, except a higher proportion of patients with positive hepatitis B envelope antigen in the nonswitch group at the initiation of ETV therapy. The LAM switch group had significantly lower 1-year relapse rate of HBV within 1 year compared to the nonswitch group (14.3% vs. 75%, p<0.001). However, none of the 48 historical control patients developed relapse of HBV, which was significantly lower than the rate in LAM switch group (p < 0.001). LAM switch was the only factor associated with HBV DNA relapse. In conclusion, continuous long-term potent nucleot(s)ide analogue therapy is mandatory for prevention of viral relapse in CHB patients.



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Use of medication reminders in patients with rheumatoid arthritis

Abstract

Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites—54 % vs Blacks—30 % vs Hispanics—26 %, p = 0.003), and sex (males—50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed—21 % vs unemployed—43 %, p = 0.006). Use of calendars was associated with adherence while away from home (ρ = 0.16, p = 0.03), when busy (ρ = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (ρ = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (ρ = −0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence.

http://ift.tt/2c0A4ne

Benefit of health education by a training nurse in patients with axial and/or peripheral psoriatic arthritis: A systematic literature review

Abstract

The aim of this study was to systematically review the literature available about the benefit of health education by a training nurse in patients with axial and/or peripheral psoriatic arthritis in the framework of the drawing up of the axial spondyloarthritis and psoriatic arthritis guidelines of the "Spanish Society of Rheumatology". Electronic databases (Cochrane Central Register of Controlled Trials, EMBASE, Medline/PubMed, CINAHL) were systematically searched from inception to 2014 using medical subject headings and keywords. Only articles in English, Spanish and French were included. The patients studied had to be diagnosed of psoriatic arthritis (all ages, both sexes) with axial involvement and/or peripheral arthritis who had received health education by a specialized nurse. We included in the search randomized clinical trials, cohort observational studies, descriptive studies and case series and qualitative research studies. Measured outcomes were those related to the education provided in a nursing consultation such as increased adherence to biological therapy, conducting exercises, smoking cessation and patient satisfaction. Eight studies were included, five randomized clinical trials with moderate level of quality and three intervention studies with no control group with low level of quality. Meta-analyses were not undertaken due to clinical heterogeneity. According to our results, it can be concluded that although there is little evidence on the role of a trained nurse in patients with psoriatic arthritis, this role can be beneficial to the patients because it can increase the rate of adherence to treatment prescribed by a rheumatologist, promotes patient self-management of their disease and increases patient satisfaction.

http://ift.tt/2dQJq1w

Prevalence and significance of MEFV gene mutations in patients with gouty arthritis

Abstract

Gouty arthritis is a chronic erosive autoinflammatory disease. Pyrin has anti-inflammatory effects in the regulation of inflammasome and is encoded by the MEFV gene. The relationship between different rheumatic diseases and the MEFV gene mutations was demonstrated. The aim of this study was to determine the frequency of MEFV gene mutations in patients with gouty arthritis and identify a possible correlation with disease phenotype. Ninety-three patients with gouty arthritis and 102 healthy controls, compatible with age, gender and ethnicity, were included in the study. MEFV gene mutations were investigated by PCR method. Out of 93 patients with gouty arthritis, 36 (38.7 %) showed MEFV gene mutations carriage, whereas 20.6 % in healthy control group. Distribution of mutations identified in patients with gouty arthritis was as; R202Q in 18 (19.3 %), E148Q in 5 (5.4 %), K695R in 4 (4.3 %), M680I in 2 (2.1 %), V726A in 2 (2.1 %), P369S in 2 (2.1 %), R408Q in 2 (2.1 %), M694 V in 1 (1.1 %), respectively. Three patients were identified with compound heterozygosity. Distribution of MEFV gene mutations carriage in healthy controls was; E148Q in 11 (10.7 %), M694 V in 2 (1.9 %), M694I in 1 (0.9 %), M680I in 2 (1.9 %), V726A in 1 (0.9 %), A744S in 1 (0.9 %), K695R in 2 (1.9 %), and P369S in 1 (0.9 %) patients, respectively. Higher MEFV gene mutations carrier frequency was observed in patients with gouty arthritis, compared with the control group (p = 0.009). Heterozygous R202Q was the most common mutation detected in patients with gouty arthritis, while heterozygous E148Q in healthy control group. Statistically significant difference was not detected between clinical findings of gouty arthritis and the MEFV gene mutations (p > 0.05). We determined higher prevalence of MEFV gene mutations in patients with gouty arthritis compared with the healthy control group. The most frequently detected mutation was heterozygous R202Q, whereas E148Q in healthy controls. High carriage rates of MEFV gene mutations in gouty arthritis suggest that it may play an important role in the pathogenesis of the disease and predisposition to the disease.

http://ift.tt/2dz386J

Small intestinal injury in NSAID users suffering from rheumatoid arthritis or osteoarthritis

Abstract

The goal of this prospective study was to assess non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) by means of non-invasive wireless capsule enteroscopy. A total of 143 patients (74 with RA, 69 with OA) treated with NSAIDs (>1 month) and 42 healthy volunteers were included. All subjects underwent capsule endoscopy, laboratory tests and filled in questionnaires. The severity of small bowel injury was graded as: mild (red spots or sporadic erosions), moderate (10–20 erosions) or severe (>20 erosions or ulcers). Capsule endoscopy identified small bowel lesions in 44.8 % of patients (mild 36.4 %, moderate 3.5 % and severe in 4.9 %). Mild non-specific lesions were found in 11.9 % healthy volunteers. There was a significantly higher prevalence of enteropathy in RA (56.8 %) compared to OA (31.9 %, p < 0.01). A significant difference between NSAID users (RA and OA) with and without enteropathy was observed in erythrocytes (p < 0.01), the leucocyte count (p < 0.05), haemoglobin (p < 0.05), haematocrit (p < 0.05), serum albumin (p < 0.01) and erythrocyte sedimentation rate (p < 0.05). No relationship was found between enteropathy and dyspepsia, gender or age. NSAID therapy is associated with a significant risk of small bowel injury. The risk is significantly higher in RA patients suggesting a possible influence of the underlying disease.

Trial registration number: DRKS00004940.

http://ift.tt/2dQGZfC

An ultrasonographic study of enthesis in early psoriatic arthritis patients naive to traditional and biologic DMARDs treatment

Abstract

The aim of this study was to evaluate the rate of power Doppler ultrasound (PDUS) abnormalities at entheseal sites in patients with early psoriatic arthritis (PsA) naïve to traditional and biologic DMARDs and to compare the PDUS findings with clinical examination. PsA patients with early disease and naïve to traditional and biologic DMARDs were consecutively enrolled in this study. Patients underwent PDUS examination of the following bilateral entheseal sites: common extensor tendon at its insertion at the lateral humeral epicondyle; quadriceps tendon at its insertion at the superior pole of the patella; patellar tendon at its insertion at the tibial tuberosity; medial collateral ligament at its proximal insertion and Achilles tendon at its insertion at the calcaneus. The Leeds enthesitis index (LEI) was used to assess clinical entheseal involvement. Twenty-one early PsA patients completed the clinical and PDUS examinations. Clinical entheseal involvement was found in 9 (42.9 %) and PDUS abnormalities in 20 (95.5 %) of the 21 early PsA patients. Achilles tendon insertion was the site with the major entheseal abnormalities. Active (power Doppler positive) entheseal lesions were found in 4.7, 9.5, 14.3 and 14.3 % of patients at the lateral humeral epicondyle; quadriceps tendon, patellar tendon insertions, and Achilles tendon insertions, respectively. Concordance between clinical (LEI) and PDUS was poor. The present study confirms that PDUS allows detecting structural and inflammatory abnormalities of enthesis in early PsA patients. Our study shows that, in early disease, active abnormalities seem to have a low prevalence.

http://ift.tt/2dz22rE

Prospective multicenter registration study of colorectal cancer: significant variations in radicality and oncosurgical quality—Swiss Group for Clinical Cancer Research Protocol SAKK 40/00

Abstract

Purpose

This study aimed to investigate in a multicenter cohort study the radicality of colorectal cancer resections, to assess the oncosurgical quality of colorectal specimens, and to compare the performance between centers.

Methods

One German and nine Swiss hospitals agreed to prospectively register all patients with primary colorectal cancer resected between September 2001 and June 2005. The median number of eligible patients with one primary tumor included per center was 95 (range 12–204).

Results

The following variations of median values or percentages between centers were found: length of bowel specimen 20–39 cm (25.8 cm), maximum height of mesocolon 6.5–12.5 cm (9.0 cm), number of examined lymph nodes 9–24 (16), distance to nearer bowel resection margin in colon cancer 4.8–12 cm (7 cm), and in rectal cancer 2–3 cm (2.5 cm), central ligation of major artery 40–97 % (71 %), blood loss 200–500 ml (300 ml), need for perioperative blood transfusion 5–40 % (19 %), tumor opened during mobilization 0–11 % (5 %), T4-tumors not en-bloc resected 0–33 % (4 %), inadvertent perforation of mesocolon/mesorectum 0–8 % (4 %), no-touch isolation technique 36–86 % (67 %), abdominoperineal resection for rectal cancer 0–30 % (17 %), rectal cancer specimen with circumferential margin ≤1 mm 0–19 % (10 %), in-hospital mortality 0–6 % (2 %), anastomotic leak or intra-abdominal abscess 0–17 % (7 %), re-operation 0–17 % (8 %).

Conclusion

In colorectal cancer, surgery considerable variations between different centers were found with regard to radicality and oncosurgical quality, suggesting a potential for targeted improvement of surgical technique.

http://ift.tt/2dQGYs4

Candidate tumor suppressor gene MCPH1 is mutated in colorectal and gastric cancers

http://ift.tt/2dz1G4x

Associations between musculoskeletal pain and work-related factors among public service sector computer workers in Kaunas County, Lithuania

Abstract

Background

Information technologies in occupational activities have been developing very rapid. Epidemiological studies have shown that musculoskeletal disorders are widely prevalent among employees working with a computer. The aim of this study was to evaluate the prevalence of musculoskeletal pain in various anatomical areas and its associations with individual, ergonomic, and psychosocial factors among computer workers of the public sector in Kaunas County, Lithuania.

Methods

The investigation consisting of two parts – questionnaire study (Nordic Musculoskeletal Questionnaire and Copenhagen Psychosocial Questionnaire) and direct observation (evaluation of work ergonomics using the Rapid Upper Limb Assessment [RULA]) – was carried out in three randomly selected public sector companies of Kaunas County. The representative study sample comprised 513 public service office workers. The prevalence of musculoskeletal pain in five anatomical areas of the body (shoulders, elbows, wrists/hands, as well as upper and low back) was evaluated.

Results

The prevalence rates of shoulder, elbow, wrist/hand, upper and low back pain were 50.5 %, 20.3 %, 26.3 %, 44.8 %, and 56.1 %, respectively. Individual factors such as gender, age, computer work experience, and body mass index were found as significant for musculoskeletal pain in various musculoskeletal regions. The respondents reporting pain in shoulder, wrist/hand, upper back, and low back areas had a statistically significantly higher mean RULA score. The duration of working with a computer was found as a significant factor for shoulder pain. High quantitative demands were related to musculoskeletal pain in all investigated anatomical areas expect for the low back; weak social support was a significant predictor for complaints in upper and low back areas.

Conclusion

This study confirmed associations between musculoskeletal pain and work ergonomics; therefore, preventive measures at the workplace should be directed to the improvement in ergonomic work environment, education, and workload optimization.

http://ift.tt/2dQFiP9

Increasing comorbidity is associated with worsening physical function and pain after primary total knee arthroplasty

Abstract

Background

Previous studies suggested that pre-operative comorbidity was a risk factor for worse outcomes after TKA. To our knowledge, studies have not examined whether postoperative changes in comorbidity impact pain and function outcomes longitudinally. Our objective was to examine if increasing comorbidity postoperatively is associated with worsening physical function and pain after primary total knee arthroplasty (TKA).

Methods

We performed a retrospective chart review of veterans who had completed Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form-36 (SF36) surveys at regular intervals after primary TKA. Comorbidity was assessed using a variety of scales: validated Charlson comorbidity index score, and a novel Arthroplasty Comorbidity Severity Index score (Including medical index, local musculoskeletal index [including lower extremity and spine] and TKA-related index subscales; higher scores are worse ), at multiple time-points post-TKA. We used mixed model linear regression to examine the association of worsening comorbidity post-TKA with change in WOMAC and SF-36 scores in the subsequent follow-up periods, controlling for age, length of follow-up, and repeated observations.

Results

The study cohort consisted of 124 patients with a mean age of 71.7 years (range 58.6–89.2, standard deviation (SD) 6.9) followed for a mean of 4.9 years post-operatively (range 1.3–11.4; SD 2.8). We found that post-operative worsening of the Charlson Index score was significantly associated with worsening SF-36 Physical Function (PF) (beta coefficient (ß) = -0.07; p < 0.0001), SF-36 Bodily Pain (BP) (ß = -0.06; p = 0.002), and WOMAC PF subscale (ß = 0.08; p < 0.001; higher scores are worse) scores, in the subsequent periods. Worsening novel medical index subscale scores were significantly associated with worsening SF-36 PF scores (ß = -0.03; p = 0.002), SF-36 BP (ß = -0.04; p < 0.001) and showed a non-significant trend for worse WOMAC PF scores (ß = 0.02; p = 0.11) subsequently. Local musculoskeletal index subscale scores were significantly associated with worsening SF-36 PF (ß = -0.05; p = 0.001), SF-36 BP (ß = -0.04; p = 0.03) and WOMAC PF (ß = 0.06; p = 0.01) subsequently. None of the novel index subscale scores were significantly associated with WOMAC pain scores. TKA complications, as assessed by TKA-related index subscale,  were not significantly associated with SF-36 or WOMAC domain scores.

Conclusions

Increasing Charlson index as well as novel medical and local musculoskeletal index subscale scores (from novel Arthroplasty  Comorbidity Severity Index) post-TKA correlated with subsequent worsening of physical function and pain outcomes post-TKA. Further studies should examine which comorbidity management could have the greatest impact on these outcomes.

http://ift.tt/2dz2Mgx

Effect of aprepitant, a moderate CYP3A4 inhibitor, on bosutinib exposure in healthy subjects

Abstract

Purpose

Bosutinib is an oral, dual Src and Abl tyrosine kinase inhibitor (TKI) approved for the treatment of Philadelphia chromosome—positive chronic myeloid leukemia resistant or intolerant to prior TKI therapy. Bosutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, suggesting drug interaction potential with other CYP3A4 modulators. This open-label, randomized, 2-sequence, 2-period crossover study assessed the effect of single-dose aprepitant, a moderate CYP3A4 inhibitor, on the single-dose pharmacokinetic profile of oral bosutinib 500 mg.

Methods

Nineteen healthy, fed adults received bosutinib (100 mg × 5) alone or coadministered with aprepitant (125 mg × 1) in each treatment period (with a ≥14-day washout); serial blood samples were analyzed. Safety was evaluated.

Results

Following coadministration of aprepitant with bosutinib, the area under the concentration-time curve from time zero extrapolated to infinity (AUC_inf) and maximum plasma concentration (C _max) were higher than in bosutinib alone (AUC_inf, 4719 and 2268 ng•h/mL; C _max, 146.0 and 94.94 ng/mL). For bosutinib with aprepitant versus bosutinib alone, mean terminal elimination half-life was similar (25.99 vs 27.79 h), time to C _max was longer (6.02 vs 4.15 h), and apparent oral clearance (CL/F) was decreased (105.9 vs 220.4 L/h). The ratio of adjusted geometric means of AUC_inf and C _max for bosutinib with aprepitant relative to bosutinib alone were 199 % (90 % confidence interval, 167–237 %) and 153 % (127–184 %), respectively. Both treatments were well tolerated.

Conclusion

In healthy volunteers, administering a single dose of aprepitant increased the AUC and C _max following a single dose of bosutinib by 99 and 53 %, respectively. These results are consistent with a moderate CYP3A4 inhibitor effect of aprepitant on bosutinib (Trial Registration: ClinicalTrials.gov NCT02058277).

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Effect of bosutinib on the absorption of dabigatran etexilate mesylate, a P-glycoprotein substrate, in healthy subjects

Abstract

Purpose

Bosutinib, a dual Src and Abl tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia, demonstrated concentration-dependent inhibitory effects on P-glycoprotein (P-gp)-mediated digoxin efflux in vitro, suggesting that bosutinib may inhibit P-gp substrates. The effect of bosutinib on dabigatran etexilate mesylate (EM) absorption, a P-gp substrate, was evaluated.

Methods

In this open-label, randomized, single-dose, one-cohort, two-sequence, two-period crossover study, healthy, fed subjects received dabigatran EM (150 mg × 1 orally) alone or 1 h after receiving bosutinib tablets (100 mg × 5 orally).

Results

Dabigatran EM monotherapy and concurrent administration of dabigatran EM with bosutinib resulted in similar values for concentration time curves from time zero extrapolated to infinity (AUC_inf), but slightly lower maximum plasma concentration (C _max) values (AUC_inf, 1182 and 1186 ng·h/mL, respectively; C _max, 129.8 and 114.1 ng/mL). The time to maximum concentration for dabigatran was 2.99 and 3.99 h for combination therapy. The ratio of the adjusted geometric means (test/reference) of dabigatran AUC_inf and C_max (90 % confidence interval) were 101.4 % (89.6–114.9 %) and 89.7 % (77.8–103.4 %), respectively, following administration of dabigatran EM with bosutinib (test) relative to dabigatran EM administered alone (reference). Six subjects receiving combination treatment reported a total of seven adverse events (AEs) versus none for subjects receiving monotherapy alone. All AEs were mild to moderate and considered treatment related.

Conclusion

These data demonstrate that single doses of bosutinib do not affect dabigatran exposure, suggesting that bosutinib is not a clinical inhibitor of P-gp.

Trial registration

ClinicalTrials.gov NCT02102633. http://ift.tt/2dz1gem

http://ift.tt/2dQFUo4

Surgical Outcomes for the Ruptured Hepatocellular Carcinoma: Multicenter Analysis with a Case-Controlled Study

Abstract

Background

While spontaneously ruptured hepatocellular carcinoma (HCC) has a poor prognosis, the true impact of a rupture on survival after hepatic resection is unclear.

Methods

Fifty-eight patients with ruptured HCC and 1922 with non-ruptured HCC underwent hepatic resection between 2000 and 2013. To correct the difference in the clinicopathological factors between the two groups, propensity score matching (PSM) was used at a 1:1 ratio, resulting in a comparison of 42 patients/group. We investigated outcomes in all patients with ruptured HCC and compared outcomes between the two matched groups.

Results

Of the 58 patients with ruptured HCC, 7 patients (13 %) died postoperatively. Overall survival (OS) rate at 5 years after hepatic resection was 37 %. Emergency hepatic resection was an independent risk factor for in-hospital death and Child-Pugh class B for unfavorable OS in multivariate analysis. Clinicopathological variables were well-balanced between the two groups after PSM. No significant differences were noted in incidence of in-hospital death (ruptured HCC 12 % vs non-ruptured HCC 2 %, p = 0.202) or OS rate (5/10-year; 42 %/38 % vs 67 %/30 %, p = 0.115).

Conclusion

Emergency hepatic resection should be avoided for ruptured HCC in Child-Pugh class B patients. Rupture itself was not a risk for unfavorable surgical outcomes.

http://ift.tt/2dFWqrB

Multifocal Versus Solitary Papillary Thyroid Carcinoma

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Surgery-Related Muscle Loss and Its Association with Postoperative Complications After Major Hepatectomy with Extrahepatic Bile Duct Resection

Abstract

Background

Several studies have reported that preoperative sarcopenia negatively impacts postoperative outcomes. Meanwhile, changes in skeletal muscle mass during the acute phase after surgery and their association with postoperative complications are unknown.

Objective

The objective of this study was to investigate the relation between changes in skeletal muscle mass and postoperative complications after major hepatectomy with extrahepatic bile duct resection.

Methods

This study included 254 patients who underwent major hepatectomies with extrahepatic bile duct resections. Total psoas muscle area (TPA) was measured using abdominal computed tomography images obtained before and 1 week after surgery. The percent change in TPA after surgery was calculated. Patients were stratified by sex-specific tertiles according to the extent of muscle mass change by percentage. Surgery-related muscle loss (SML) was defined as the lowest tertile of percent change in TPA.

Results

Male patients with a percent change of TPA lower than −5.0 % (n = 54) and female patients with that lower than −2.6 % (n = 31) were included in the lowest tertile and were categorized into a group with SML. The incidence rates of major complications, pancreatic fistula, infectious complications, and mortality were all significantly higher in the group with SML than in the group without SML. By multivariate analyses, SML was identified as an independent factor associated with major complications (odds ratio 3.21; 95 % confidential interval 1.82–5.76, p < 0.001).

Conclusions

SML is significantly associated with postoperative morbidity and mortality in patients who underwent major hepatectomies with extrahepatic bile duct resections.

http://ift.tt/2dL5ygK

A Clear Difference Between the Outcomes After a Major Hepatectomy With and Without an Extrahepatic Bile Duct Resection

Abstract

Background

The procedure of a simple hepatectomy and a hepatectomy with an extrahepatic bile duct resection and subsequent choledocho-jejunostomy is largely different. However, these two procedures are sometimes included in the same category. There are no studies comparing postoperative course and liver regeneration rate after a major hepatectomy with and without an extrahepatic bile duct resection.

Methods

We retrospectively reviewed medical records of 245 patients who underwent a right hepatectomy (RH, n = 55) or RH with an extrahepatic bile duct resection (RHEBR, n = 190). Postoperative complications, including incidence of posthepatectomy liver failure (PHLF) and hepatic regeneration rates after surgery, were evaluated.

Results

The incidence of PHLF was considerably higher in the RHEBR group than in the RH group (39.5 vs. 16.4 %, p = 0.001). The percentage of newly regenerated liver volume after the hepatectomies on postoperative days 6–8 was significantly lower in the RHEBR group than in the RH group (14.0 % in the RH; 7.9 % in the RHEBR group, p < 0.001). Especially type of surgery (RHEBR) was the only independent risk factor for an impaired liver regeneration rate by univariate and multivariate analyses. Furthermore, estimated hepatic regeneration rate by stepwise linear regression analysis in the RHEBR group was 7.1 % lower (95 % confidence interval 1.8–12.3, p = 0.011) than in the RH group.

Conclusion

These results suggest that the procedure of extrahepatic bile duct resection has a possibility of adverse impact on the postoperative outcome after major hepatectomy.

http://ift.tt/2cXCV0l

Sublobar Resection Margin Width Does Not Affect Recurrence of Clinical N0 Non-small Cell Lung Cancer Presenting as GGO-Predominant Nodule of 3 cm or Less

Abstract

Background

Sublobar resection of lung cancer may benefit patients with lung cancer presenting as ground-glass opacity (GGO) nodules. The purpose of this study was to evaluate the effect of margin width on recurrence after sublobar resection in patients with clinical N0 non-small cell lung cancer presenting as GGO-predominant nodule.

Methods

We conducted a retrospective chart review of 91 patients treated for clinical N0 non-small cell lung cancer ≤3 cm by sublobar resection with clear resection margins. We assigned them to two groups: GGO-predominant tumor and solid-predominant tumor. Each group was subdivided into two groups according to the margin width: resection margin ≤5 mm and resection margin >5 mm. We analyzed the clinicopathological findings and survival among these four groups.

Results

There was no recurrence in GGO-predominant tumors after sublobar resection. Margin width did not influence the recurrence in GGO-predominant tumors. In the cases of solid-predominant tumor, 5-year recurrence-free survival after sublobar resection according to margin width ≤5 and >5 mm was 24.2 and 79.6 %, respectively (p < 0.001). Therefore, narrow margin width (resection margin ≤5 mm) was a significant risk factor for recurrence of solid-predominant tumors (hazard ratio 3.868, 95 % confidence interval 1.177–12.714, p = 0.026).

Conclusions

The width between the tumor and resection margin does not affect the recurrence after R0 sublobar resection in patients with clinical N0 GGO-predominant lung cancer ≤3 cm. By contrast, margin width is a significant risk factor for recurrence after sublobar resection in patients with clinical N0 solid-predominant lung cancer.

http://ift.tt/2dkKMBk

Readmissions After Surgery: A French Nationwide Cross-Sectional Study of 1,686,602 Procedures Performed in 2010

Abstract

Background

Surgical readmissions have been extensively studied in North America, but very few data from other countries are available. We aimed to describe surgical readmissions in France and to assess their association with hospital status, surgical volume, and day surgery activity.

Methods

We performed a cross-sectional study encompassing all 1270 French hospitals, except for military hospitals and hospitals with very small volume. Data were retrieved from the national database regarding all patients undergoing surgery between January 1, 2010 and November 30, 2010. The main outcome measure was 30-day readmission rate. Association with hospital status, surgical volume, and the level of day surgery were assessed. Risk adjustment was performed based upon administrative categories.

Results

After exclusion of deaths and hospital transfers, there were 1,686,602 patients in the study cohort. Thirty-day readmission rate was 5.9 %. Distribution was skewed, with 21.5 % of procedures accounting for 33.5 % of all 30-day readmissions. Early readmissions (≤3 days) were associated with higher mortality as compared to those occurring later (>7 days) (3.2 vs. 2.6 %; p < 0.0001). After multivariate analysis, University hospitals were shown to be affected by a significantly greater risk of 30-day readmission as compared to private hospitals (odds ratio 1.46 [95 % CI 1.42–1.5]). Other independent factors were as follows: male gender, longer initial hospital stay, and comorbidities.

Conclusions

Surgical 30-day readmission rate was low, with early readmissions being associated with higher mortality. Conversely to prior research, University hospitals were shown to be associated with significantly higher risk of 30-day readmissions, even after risk adjustment.

http://ift.tt/2dAEb7i

Thermomechanically coupled conduction mode laser welding simulations using smoothed particle hydrodynamics

Abstract

Process simulations of conduction mode laser welding are performed using the meshless Lagrangian smoothed particle hydrodynamics (SPH) method. The solid phase is modeled based on the governing equations in thermoelasticity. For the liquid phase, surface tension effects are taken into account to simulate the melt flow in the weld pool, including the Marangoni force caused by a temperature-dependent surface tension gradient. A non-isothermal solid–liquid phase transition with the release or absorption of additional energy known as the latent heat of fusion is considered. The major heat transfer through conduction is modeled, whereas heat convection and radiation are neglected. The energy input from the laser beam is modeled as a Gaussian heat source acting on the initial material surface. The developed model is implemented in Pasimodo. Numerical results obtained with the model are presented for laser spot welding and seam welding of aluminum and iron. The change of process parameters like welding speed and laser power, and their effects on weld dimensions are investigated. Furthermore, simulations may be useful to obtain the threshold for deep penetration welding and to assess the overall welding quality. A scalability and performance analysis of the implemented SPH algorithm in Pasimodo is run in a shared memory environment. The analysis reveals the potential of large welding simulations on multi-core machines.

http://ift.tt/2dZPpFG

An assessment of the potential of PFEM-2 for solving long real-time industrial applications

Abstract

The latest generation of the particle finite element method (PFEM-2) is a numerical method based on the Lagrangian formulation of the equations, which presents advantages in terms of robustness and efficiency over classical Eulerian methodologies when certain kind of flows are simulated, especially those where convection plays an important role. These situations are often encountered in real engineering problems, where very complex geometries and operating conditions require very large and long computations. The advantages that the parallelism introduced in the computational fluid dynamics making affordable computations with very fine spatial discretizations are well known. However, it is not possible to have the time parallelized, despite the effort that is being dedicated to use space–time formulations. In this sense, PFEM-2 adds a valuable feature in that its strong stability with little loss of accuracy provides an interesting way of satisfying the real-life computation needs. After having already demonstrated in previous publications its ability to achieve academic-based solutions with a good compromise between accuracy and efficiency, in this work, the method is revisited and employed to solve several nonacademic problems of technological interest, which fall into that category. Simulations concerning oil–water separation, waste-water treatment, metallurgical foundries, and safety assessment are presented. These cases are selected due to their particular requirements of long simulation times and or intensive interface treatment. Thus, large time-steps may be employed with PFEM-2 without compromising the accuracy and robustness of the simulation, as occurs with Eulerian alternatives, showing the potentiality of the methodology for solving not only academic tests but also real engineering problems.

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Hydrocodone Bitartrate ER (Hysingla ® ER): A Review in Chronic Pain

Abstract

Hydrocodone bitartrate extended-release (Hysingla^® ER; referred to hereafter as hydrocodone ER) was the first single-entity hydrocodone formulation recognized by the US FDA as having abuse-deterrent properties. It is indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Once-daily oral hydrocodone ER provides consistent plasma hydrocodone concentrations and sustained analgesia over the 24-h dosing interval. Its physicochemical properties render hydrocodone ER harder to manipulate physically, which is expected to deter intranasal, intravenous and oral abuse. For instance, oral hydrocodone ER (intact or chewed) significantly reduced drug liking relative to hydrocodone solution in a clinical study. In two large phase III studies in patients with chronic pain, hydrocodone ER reduced pain intensity, with its effects seen early (during dose titration) and maintained during ≤76 weeks' treatment. During maintenance therapy, the majority of patients continued hydrocodone ER at the dosage achieved at the end of dose titration and without requiring increased doses of supplemental pain medication, suggesting adequate pain management. Hydrocodone ER was generally well tolerated, with a safety profile consistent with that seen with other μ-opioid analgesics. However, like other opioids, it is associated with risks of addiction, abuse/misuse and serious adverse events (AEs), including respiratory depression, withdrawal, physical dependence and overdose. Although large postmarketing studies are needed to determine whether the abuse-deterrent properties of hydrocodone ER result in meaningful reductions in abuse, misuse and related adverse clinical outcomes, current evidence indicates that hydrocodone ER is a useful treatment option for patients with chronic pain.

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Hybrid PET/MR: Updated Clinical Use and Potential Applications

Abstract

Purpose of Review

Simultaneous positron emission tomography/magnetic resonance was released few years ago and there is a (non-official) perspective of almost 100 scanners worldwide being installed until 2016. Despite the enormous marketing success for such an expensive and fine hybrid imaging tool, PET/MR is still seen primarily as a research tool. Currently this clinical validation process is more than necessary to justify the additional expenses in a world with increasing difficulties regarding health system reimbursement.

Recent Findings

The current PET/MR feasibility has been demonstrated with the published data so far in almost every body region, with great potential applications. The main fields of research in PET/MR are oncologic and neurologic, basically for two reasons: (1) because almost 90 % of PET/CT studies come from oncology; (2) and also because of the recent development of new medications and treatments for dementia, making PET/MR an important character in this new scenario. Inflammation has become the newest potential application, and will also be discussed further on.

Summary

In this article such potential clinical PET/MR applications are compiled and updated and will be thoroughly discussed.

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From “ear” to there: a review of biorobotic models of auditory processing in lizards

Abstract

The peripheral auditory system of lizards has been extensively studied, because of its remarkable directionality. In this paper, we review the research that has been performed on this system using a biorobotic approach. The various robotic implementations developed to date, both wheeled and legged, of the auditory model exhibit strong phonotactic performance for two types of steering mechanisms—a simple threshold decision model and Braitenberg sensorimotor cross-couplings. The Braitenberg approach removed the need for a decision model, but produced relatively inefficient robot trajectories. Introducing various asymmetries in the auditory model reduced the efficiency of the robot trajectories, but successful phonotaxis was maintained. Relatively loud noise distractors degraded the trajectory efficiency and above-threshold noise resulted in unsuccessful phonotaxis. Machine learning techniques were applied to successfully compensate for asymmetries as well as noise distractors. Such techniques were also successfully used to construct a representation of auditory space, which is crucial for sound localisation while remaining stationary as opposed to phonotaxis-based localisation. The peripheral auditory model was furthermore found to adhere to an auditory scaling law governing the variation in frequency response with respect to physical ear separation. Overall, the research to date paves the way towards investigating the more fundamental topic of auditory metres versus auditory maps, and the existing robotic implementations can act as tools to compare the two approaches.

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White-Tailed Deer as an Ex Vivo Knee Model: Joint Morphometry and ACL Rupture Strength

Abstract

Animal joints are valuable proxies for those of humans in biomechanical studies, however commonly used quadruped knees differ greatly from human knees in scale and morphometry. To test the suitability of the cervine stifle joint (deer knee) as a laboratory model, gross morphometry, ACL cross section, and ACL rupture strength were measured and compared to values previously reported for the knees of humans and commonly studied animals. Twelve knee joints from wild white-tailed deer were tested. Several morphometry parameters, including bicondylar width (53.5 ± 3.0 mm) and notch width (14.7 ± 2.5 mm), showed a high degree of similarity to those of the human knee, while both medial (16.7 ± 2.1°) and lateral (17.6 ± 4.7°) tibial slopes were steeper than in humans but less steep than other quadrupeds. The median ACL rupture force (2054 N, 95% CI 2017–2256 N), mean stiffness (260 ± 166 N/mm), mean length (33 ± 7 mm), and mean cross sectional area (44.8 ± 18.3 mm²) were also comparable to previously reported values for human knees. In our limited sample size, no significant sexual dimorphism in strength or morphometry was observed (p ≥ 0.05 for all parameters), though female specimens generally had steeper tibial slopes (lateral: p = 0.52, medial: p = 0.07). Our results suggest that the deer knee may be a suitable model for ex vivo studies of ACL rupture and repair.

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In Silico and In Vivo Experiments Reveal M-CSF Injections Accelerate Regeneration Following Muscle Laceration

Abstract

Numerous studies have pharmacologically modulated the muscle milieu in the hopes of promoting muscle regeneration; however, the timing and duration of these interventions are difficult to determine. This study utilized a combination of in silico and in vivo experiments to investigate how inflammation manipulation improves muscle recovery following injury. First, we measured macrophage populations following laceration injury in the rat tibialis anterior (TA). Then we calibrated an agent-based model (ABM) of muscle injury to mimic the observed inflammation profiles. The calibrated ABM was used to simulate macrophage and satellite stem cell (SC) dynamics, and suggested that delivering macrophage colony stimulating factor (M-CSF) prior to injury would promote SC-mediated injury recovery. Next, we performed an experiment wherein 1 day prior to injury, we injected M-CSF into the rat TA muscle. M-CSF increased the number of macrophages during the first 4 days post-injury. Furthermore, treated muscles experienced a swifter increase in the appearance of PAX7⁺ SCs and regenerating muscle fibers. Our study suggests that computational models of muscle injury provide novel insights into cellular dynamics during regeneration, and further, that pharmacologically altering inflammation dynamics prior to injury can accelerate the muscle regeneration process.

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Biosynthesis of nanoparticles of metals and metalloids by basidiomycetes. Preparation of gold nanoparticles by using purified fungal phenol oxidases

Abstract

The work shows the ability of cultured Basidiomycetes of different taxonomic groups—Lentinus edodes, Pleurotus ostreatus, Ganoderma lucidum, and Grifola frondosa—to recover gold, silver, selenium, and silicon, to elemental state with nanoparticles formation. It examines the effect of these metal and metalloid compounds on the parameters of growth and accumulation of biomass; the optimal cultivation conditions and concentrations of the studied ion-containing compounds for recovery of nanoparticles have been identified. Using the techniques of transmission electron microscopy, dynamic light scattering, X-ray fluorescence and X-ray phase analysis, the degrees of oxidation of the bioreduced elements, the ζ-potential of colloidal solutions uniformity, size, shape, and location of the nanoparticles in the culture fluid, as well as on the surface and the inside of filamentous hyphae have been determined. The study has found the part played by homogeneous chromatographically pure fungal phenol-oxidizing enzymes (laccases, tyrosinases, and Mn-peroxidases) in the recovery mechanism with formation of electrostatically stabilized colloidal solutions. A hypothetical mechanism of gold(III) reduction from HAuCl₄ to gold(0) by phenol oxidases with gold nanoparticles formation of different shapes and sizes has been introduced.

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Incubation of innovative methanogenic communities to seed anaerobic digesters

Abstract

The methanogenic communities in alternative inocula and their potential to increase CH₄ production in mesophilic and psychrophilic dairy manure-based anaerobic digesters were examined. Quantitative-PCR and terminal restriction fragment length polymorphism (T-RFLP) profiles were used to determine archaeal and methanogenic community changes when three inocula (wetland sediment (WS), landfill leachate (LL), and mesophilic digestate (MD)) were incubated at 15, 25, and 35 °C for 91 and 196 days. After each incubation period, the inocula were used in biochemical methane potential (BMP) tests at the incubation temperatures. There was no significant correlation between inoculum mcrA gene copy numbers and CH₄ produced in BMP tests, suggesting that population size was not a distinguishing characteristic for predicting CH₄ production. Archaeal composition in LL and WS reactors generally converged with MD reactors after incubation at 25 and 35 °C for 196 days. These MD reactors had high relative abundance of TRF 302, likely Methanosaetaceae, and low acetic acid (0.62–1.61 mM). At 15 °C incubation, most reactors were associated with high acetic acid (1.61–133.6 mM) and dominated by TRF 199, likely Methanosarcinaceae. The LL reactor incubated at 25 °C for 91 days had higher relative abundance of TRF 199 and produced significantly higher CH₄ than WS and MD reactors in BMP test. In the future, it may be possible to create enrichment cultures that favor particular methanogens and use them as inoculum to benefit digesters at low mesophilic temperatures. Our data provides evidence that tailoring the archaeal community could benefit digesters operating under different conditions.

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A unique intracellular compartment formed during the oligotrophic growth of Rhodococcus erythropolis N9T-4

Abstract

Rhodococcus erythropolis N9T-4, isolated from stored crude oil, shows extremely oligotrophic features and can grow on a basal medium without any additional carbon, nitrogen, sulfur, and energy sources, but requires CO₂ for its oligotrophic growth. Transmission electron microscopic observation showed that a relatively large and spherical compartment was observed in a N9T-4 cell grown under oligotrophic conditions. In most cases, only one compartment was observed per cell, but in some cases, it was localized at each pole of the cell, suggesting that it divides at cell division. We termed this unique bacterial compartment an oligobody. The oligobody was not observed or very rarely observed in small sizes under nutrient rich conditions, whereas additional carbon sources did not affect oligobody formation. Energy dispersive X-ray spectroscopy analysis revealed remarkable peaks corresponding to phosphorus and potassium in the oligobody. The oligobodies in N9T-4 cells could be stained by Toluidine blue, suggesting that the oligobody is composed of inorganic polyphosphate and is a type of acidocalcisome. Two genes-encoding polyphosphate kinases, ppk1 and ppk2, were found in the N9T-4 genome: ppk1 disruption caused a negative effect on the formation of the oligobody. Although it was suggested that the oligobody plays an important role for the oligotrophic growth, both ppk-deleted mutants showed the same level of oligotrophic growth as the wild-type strain.

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Quantitative method for determination of oleocanthal and oleacein in virgin olive oils by liquid chromatography–tandem mass spectrometry

Publication date: 1 January 2017
Source:Talanta, Volume 162
Author(s): Verónica Sánchez de Medina, Hristofor Miho, Eleni Melliou, Prokopios Magiatis, Feliciano Priego-Capote, María Dolores Luque de Castro
Oleocanthal and oleacein, two key secoiridoid derivatives present in virgin olive oil (VOO), are gaining clinical and nutritional interest thanks to their proved bioactivity; therefore, the determination of both phenols is a growing demanded application to increase the value of VOO. The main problem of previously reported liquid chromatography-based methods for oleocanthal and oleacein measurement is their interaction with water or other polar solvents such as methanol to promote the formation of hemiacetal or acetal derivatives. This interaction can occur during either sample extraction, basically liquid–liquid extraction, and/or chromatographic separation. The aim of this research was to evaluate the suitability of LC–MS/MS for absolute quantitation of oleocanthal and oleacein in VOO. For this purpose, both liquid–liquid extraction and chromatographic separation were studied as potential promoters of acetals and hemiacetals formation from oleocanthal and/or oleacein. The results showed that the use of methanol–water solutions for phenols extraction was not influential on the formation of these artifacts. Acetals and hemiacetals from oleocanthal and/or oleacein were only detected at very low concentrations when methanol gradients under acidic conditions were used for chromatographic separation. With this premise, a protocol based on extraction with acetonitrile and a reverse chromatographic gradient with methanol was established to quantify in absolute terms oleocanthal and oleacein in VOO samples. The resulting protocol was applied to three VOO samples characterized by high, medium, and low levels of these two phenols.



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Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9), a biomarker for various pathological conditions, is produced in post-blood collection by fibrinolysis and coagulation factors

Abstract

Background

Fibrinogen alpha C chain 5.9 kDa fragment (FIC5.9) is a new serum biomarker for chronic hepatitis that was discovered by proteomics analysis. Previous studies have shown that FIC5.9 is derived from the C-terminal region of fibrinogen alpha chain and the serum levels of FIC5.9 decrease in chronic hepatitis. It also have been reported that FIC5.9 cannot be detected in the blood stream of the systemic circulation and it is released from fibrinogen during blood clotting in collecting tube. However, the mechanism of FIC5.9 releasing from fibrinogen is unclear.

Methods

We formulated a hypothesis that FIC5.9 is released by enzymes that are activated by post-blood collection and may be coagulation and fibrinolysis factors. In this study, we analyzed the mechanisms of FIC5.9 releasing from fibrinogen in healthy blood.

Results

Our analysis showed that thrombin acts as an initiator for FIC5.9 releasing, and that mainly plasmin cleaves N-terminal end of FIC5.9 and neutrophil elastase cleave C-terminal end of FIC5.9.

Conclusion

FIC5.9 reflects minute changes in coagulation and fibrinolysis factors and may be associated with pathological conditions.

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Intestinal Lipomatosis and Chemotherapy: A Growing Concern

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Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia

Abstract

Background

In patients with functional dyspepsia (FD), mild duodenal inflammation correlates with increased mucosal permeability. Enteric glial cells can produce glial cell line-derived neurotrophic factor (GDNF) to repair disrupted epithelial barrier function.

Aims

We examined the role of duodenal GDNF in FD pathophysiology and its association with dyspeptic symptoms.

Methods

Duodenal biopsies taken from FD patients and control subjects were used for analysis. GDNF protein expression and localization were examined. Cellular infiltration of eosinophils and mast cells was measured. We also examined the intercellular space between the adjacent epithelial cells at the apical junction complex using transmission electron microscopy.

Results

In FD patients, expression of GDNF protein was significantly increased compared with controls, 107.3 (95.3–136.7) versus 49.3 (38.0–72.6) pg/mg protein (median (interquartile range), p = 0.006), respectively. GDNF was localized in enteric glial cells, eosinophils, and epithelial cells. The number of eosinophils was significantly greater in FD patients than in controls, 1039 (923–1181) versus 553 (479–598) cells/mm² (p = 0.021), respectively. The intercellular space was dilated at the adherent junction in FD patients compared to control patients, 32.4 (29.8–34.8) versus 22.0 (19.9–26.1) nm (p = 0.002), respectively. Intercellular distance positively correlated with the frequency of postprandial fullness and early satiation (p = 0.001, r = 0.837 and p = 0.009, r = 0.693, respectively). Expression of GDNF correlated with epigastric burning (p = 0.041, r = 0.552).

Conclusions

Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.

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Rapid diagnostic test and use of antibiotic against methicillin-resistant Staphylococcus aureus in adult intensive care unit

Abstract

Ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA) is associated with excess mortality and costs. Molecular biology test allows rapid identification of MRSA in sputum with high negative predictive value. We hypothesized that use of a rapid diagnostic test in patients with suspected VAP was associated with reduced use of antibiotics directed against MRSA. This retrospective, observational study was conducted in a polyvalent intensive care unit (ICU) of a university hospital. We compared two periods: before (2007–2010) and after (2010–2015) the implementation of a rapid diagnostic test, which uses RT-PCR to detect pathogens in 60 minutes. The primary endpoint was the effect on the empirical use of anti-MRSA antibiotics. The second endpoint was the effect of this strategy on the cost regarding antibiotic treatment. The first group included 120 suspected VAP (88 patients) and the second group 121 suspected VAP (89 patients). Empirical use of vancomycin and linezolid decreased by 50 % between the two periods. Twenty-seven VAP (22 %) were treated with an anti-MRSA treatment between 2007 and 2010, and 13 (11 %) between 2010 and 2015 (p = 0.04). The mean cost of anti-MRSA treatment by patients in the first group was 63 ± 223 €, and 13 ± 52 € in the second group (p < 0.001). This study shows that a rapid diagnostic test was associated with reduced use and cost of anti-MRSA antibiotics in patients with suspected VAP. These results should be confirmed by further multicenter prospective studies.

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Erratum to: Proceedings of the American Society for Enhanced Recovery/Evidence Based Peri-Operative Medicine 2016 Annual Congress of Enhanced Recovery and Perioperative Medicine

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