Journal of International Medical Research

To investigate the potential association between serum folate levels and colorectal adenoma (CRA) occurrence and recurrence.

This prospective study measured baseline serum folate levels in outpatients who were screened for CRA using colonoscopy. Participants were then randomly selected to produce one group with CRA and one without CRA. These two subgroups underwent further follow-up observations of colonoscopy to determine the occurrence of new and recurrent CRA.

A total of 1310 participants were screened at baseline: 888 were healthy subjects without CRA; and 422 had CRA. Two subgroups were randomly selected (n = 200 per group) for follow-up. In the overall population, baseline serum folate levels were significantly lower in patients with CRA or advanced CRA (A-CRA) compared with healthy participants without CRA. Similar findings were shown for the follow-up study in terms of the association between CRA and A-CRA occurrence and recurrence and baseline serum folate levels. After controlling for confounders, increased serum folate was associated with a reduced risk of occurrence of CRA (odds ratio [OR] 0.993, 95% confidence interval [CI] 0.924, 1.066) and recurrence of CRA (OR 0.749, 95% CI 0.322, 1.742).

Higher serum folate levels may be protective against CRA and/or A-CRA.

A retrospective study to determine the relationships between platelet parameters and inflammation and fibrosis of the liver in patients with chronic hepatitis B virus infection (CHB).

Patients with liver biopsy-confirmed CHB were included in the study. Liver fibrosis and inflammation were assessed by histopathology of biopsied liver tissue. Platelet count (PLT), platelet distribution width (PDW) and mean platelet volume (MPV) were determined as part of routine blood tests. The relationship between inflammation and fibrosis and platelet parameters were analysed by multiple linear regression.

The study included 677 patients. PLT and PDW accounted for 20.5% of liver inflammation. PLT and PDW accounted for 18.4% of liver fibrosis.

Platelet parameters can provide valuable information for the assessment of hepatic inflammation and fibrosis.

To determine potential risk factors that could predict stress fractures over an 8-week basic military training in Chinese male infantry recruits.

Recruits from three infantry units enrolled in this prospective study. At baseline, demographic data, personal history of stress fractures, mean duration of weekly exercise and smoking history were recorded on questionnaires and blood samples taken for analysis of bone turnover biomarkers and genetic factors.

Of the 1516 male recruits who volunteered to participate in the study, 1398 recruits provided data for analysis. In total, 189 stress fracture cases were observed (incidence rate: 13.5%) during the 8-week training period. Recruits with stress fractures had a significantly higher incidence of prior fracture history and lower exercise level prior to enrolment compared with those without stress fractures. A significant difference in both allelic frequency and genotypic distribution of the growth differentiation factor 5 (GDF5) gene rs143383 polymorphism was observed between recruits with and without stress fractures. However, no difference in serum bone turnover biomarkers was detected between groups.

This prospective, cohort study indicates that fracture history, lower exercise level and GDF5 rs143383 may be predictive risk factors for stress fractures in Chinese male infantry recruits.

To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome.

This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods.

Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0–29.9 kg/m²) and 22 had normal weight (BMI = 18.5–24.9 kg/m²). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls.

Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.

To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection.

Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2′-5′ oligoadenylate synthetase (2′-5′OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated.

Plasma Gal-9 levels were increased in patients (n = 52) compared with controls (n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2′-5′OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist.

Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.

A randomized, double-blind, prospective study to evaluate the effect of anticholinergic drugs on thermoregulation in paediatric patients undergoing ambulatory anaesthesia with ketamine.

Patients were randomized to receive either 0.005 mg/kg glycopyrrolate or the equivalent volume of normal saline (placebo) at 30 min before ketamine anaesthesia. Body temperature was measured tympanically at baseline and at 0, 30, 60 and 90 min postoperatively. The quantity of saliva prodiced during surgery and incidence of fever were recorded.

Body temperature was significantly higher in the glycopyrrolate group (n = 42) than the placebo group (n = 42) at 30, 60 and 90 min after surgery, and higher than baseline at 0, 30, 60 and 90 min after surgery. In the placebo group, body temperature was significantly higher than baseline at 0 and 30 min after surgery. Saliva secretion was significantly lower in the glycopyrrolate group than the placebo group.

Routine premedication with adjunctive anticholinergics should not be considered in paediatric patients receiving ketamine sedation due to the increased risk of fever.

Trial registration number, Clinicaltrials.gov: NCT02430272

This study evaluated the effects of vaginal and caesarean delivery on internal and external anal sphincter muscle thickness using translabial ultrasonography (TL-US).

This prospective cohort study enrolled nulliparous women who either had vaginal or caesarean deliveries. The thickness of the hypoechoic internal anal sphincter (IAS) and hyperechoic external anal sphincter (EAS) at the 12, 3, 6, and 9 o’clock positions at the distal level were measured before delivery and within 24–48 h after delivery.

A total 105 consecutive women were enrolled in the study: 60 in the vaginal delivery group and 45 in the caesarean delivery group. The IAS muscle thickness at the 12 o’clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.31 ± 0.74 mm versus 1.81 ± 0.64 mm, respectively). The EAS muscle thickness at the 12 o’clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.42 ± 0.64 mm versus 1.97 ± 0.85, respectively).

There was significant muscle thinning of both the IAS and EAS at the 12 o’clock position after vaginal delivery, but not after caesarean delivery.

Continuous invasive arterial blood pressure (IBP) monitoring remains the gold standard for BP measurement, but traditional oscillometric non-invasive intermittent pressure (NIBP) measurement is used in most low-to-moderate risk procedures. This study compared non-invasive continuous arterial BP measurement using a Nexfin® monitor with NIBP and IBP monitors.

This was a single-centre, prospective, pilot study in patients scheduled for elective orthopaedic surgery. Systolic BP, diastolic BP and mean arterial blood pressure (MAP) were measured by Nexfin®, IBP and NIBP at five intraoperative time-points. Pearson correlation coefficients, Bland–Altman plots and trending ability of Nexfin® measurements were used as criteria for success in the investigation of measurement reliability.

A total of 20 patients were enrolled in the study. For MAP, there was a sufficient correlation between IBP/Nexfin® (Pearson = 0.75), which was better than the correlation between IBP/NIBP (Pearson = 0.70). Bland–Altman analysis of the data showed that compared with IBP, there was a higher percentage error for MAP_NIBP (30%) compared with MAP_Nexfin® (27%). Nexfin® and NIBP underestimated systolic BP; NIBP also underestimated diastolic BP and MAP. Trending ability for MAP_Nexfin® and MAP_NIBP were comparable to IBP.

Non-invasive BP measurement with Nexfin® was comparable with IBP and tended to be more precise than NIBP.

A double-blind randomised study to evaluate the opioid sparing effect and safety of nefopam when administered via intravenous patient controlled analgesia (PCA) with fentanyl.

Patients planned for elective open laparotomy, were randomly assigned to receive into fentanyl 25 µg/ml (SF group) or nefopam 2.4 mg/ml plus fentanyl 25 µg/ml (NF group). Patients were assessed before surgery and for 24 h postoperatively.

Total PCA fentanyl consumption was significantly lower in the NF group (n = 35) than the SF group (n = 36). Pain scores were significantly lower and patients’ satisfaction with treatment significantly better in the NF group than the SF group. Dry mouth and dizziness were significantly more frequent in the NF group than the SF group. There were no other statistically significant between-group differences in the incidence of adverse events.

Intravenous PCA using nefopam + fentanyl following laparotomy has an opioid sparing effect and is associated with a low incidence of some of the typical opioid related adverse events.

Clinicaltrials.gov Registration No: NCT02596269

To investigate the synergistic effects of combining erlotinib and RNA-interference downregulation of focal adhesion kinase (FAK) expression on the proliferation, apoptosis, invasion and migration of the human gastric adenocarcinoma cell line AGS.

Cells were divided into five experimental groups: Group A, nontransfected control; Group B, transfected with empty vector; Group C, transfected with FAK-shRNA; Group D, erlotinib treatment; Group E, combination erlotinib treatment and transfected with FAK-shRNA. FAK protein levels were confirmed via Western blotting. Cell proliferation (CCK-8 assay, apoptosis (flow cytometry), cell invasion (transwell assay) and migration (scratch assay) were evaluated.

RNA interference significantly decreased FAK protein levels. Cell proliferation, invasion and migration were significantly lower in Groups C, D and E compared with Group A, and significantly lower in Group E than in Groups C and D.

RNA interference effectively silences FAK expression and inhibits malignant cell proliferation and invasion in gastric cancer cells. The effect of FAK inhibition is increased by co-treatment with erlotinib.

To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD).

This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay.

Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD.

Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity.

To evaluate serum micro RNA-143 (miR-143) levels in patients with sepsis or non-infectious systemic inflammatory response syndrome (SIRS), and investigate its possible diagnostic or prognostic value.

Serum was obtained from patients with sepsis or SIRS and healthy control subjects. Relative miR-143 expression was determined using quantitative real time polymerase chain reaction. The diagnostic and prognostic value of serum miR-143 was evaluated.

Serum miR-143 levels were significantly higher in patients with sepsis (n = 103) than patients with SIRS (n = 95) and healthy controls (n = 40). There were significant positive correlations between serum miR-143 level and SOFA and APACHE II scores in patients with sepsis (r = 0.794 and r = 0.825, respectively). Serum miR-143 had a sensitivity of 78.6% and specificity of 91.6% for distinguishing between sepsis and SIRS. There was no association between serum miR-143 and 28-day survival in patients with sepsis.

Serum miR-143 is elevated in patients with sepsis, and may be a useful biomarker for distinguishing between sepsis and SIRS.

To investigate the cytotoxic effects of suberanilohydroxamic acid (vorinostat) in combination with arsenic trioxide (ATO) on the human NB4 cell line in vitro.

The rates of cell proliferation following treatment with vorinostat with or without ATO were measured. Flow cytometry of Annexin-V/propidium iodide double-stained cells was used to measure apoptosis. Acridine Orange and ethidium bromide staining was used to observe morphological changes characteristic of apoptosis. Western blot analysis was used to measure protein levels.

Vorinostat and ATO, alone and in combination, inhibited the proliferation of NB4 cells in a time- and dose-dependent manner and the effect was additive. NB4 cells treated with vorinostat + ATO demonstrated greater levels of apoptosis compared with cells treated with either drug alone. Both vorinostat and ATO alone and in combination resulted in lower levels of promyelocytic leukaemia/retinoic acid receptor alpha fusion protein and increased levels of acetyl-histone H3 and acetyl-histone H4 proteins compared with controls. Vorinostat + ATO resulted in lower levels of Akt protein compared with either drug alone.

The combination of vorinostat and ATO inhibited cell proliferation, induced apoptosis, and enhanced the chemosensitivity of NB4 cells. The mechanism might be associated with increasing histone acetylation levels as well as downregulation of the Akt signalling pathway.

The diagnostic validity of clinical airway assessment tests for predicting difficult laryngoscopy in patients requiring endotracheal intubation were evaluated using receiver operating characteristic (ROC) curve analysis and a grey zone approach.

In this prospective observational study, patients were evaluated during a pre-anaesthetic visit. Predictive airway assessment tests (i.e. Modified Mallampati [MMT] classification; upper lip bite test [ULBT]; mouth opening; sternomental distance; thyromental distance [TMD]; neck circumference; neck mobility; height to thyromental distance [HT/TMD]; neck circumference-to-thyromental distance [NC/TMD]) were performed on each patient and LEMON, Naguib, and MACOCHA scores were also calculated. In addition, laryngeal images were acquired and assessed for percentage of glottic opening (POGO) scores. A POGO score of zero was categorized as difficult laryngoscopy.

The incidence of difficult laryngoscopy was 14.4% (35/243). Although seven predictive airway assessments (i.e. MMT classification, ULBT, mouth opening, HT/TMD, NC/TMD, and the LEMON and Naguib models) predicted difficult laryngoscopy by ROC analyses, a grey zone approach showed that the parameters were inconclusive in approximately 70% of patients. From all the tests, the HT/TMD ratio showed the highest sensitivity (80.0%) and ULBT had the highest specificity (95.2%).

Using the grey zone approach, all predictive airway assessment tests showed large inconclusive zones which may explain previous inconsistent results in the prediction of difficult laryngoscopy. Our results suggest that the usefulness of clinical airway evaluation tests for predicting difficult laryngoscopy remains controversial.

ClinicalTrials.gov (NCT01719848)

To assess a classification system for midfoot injury that was based on the characteristics of the foot malunion and to evaluate the suggested treatment strategies.

This retrospective review of data from patients with posttraumatic midfoot malunion categorized each foot deformity into one of three types based on the foot arch and then separated these categories into one of three subtypes based on the forefoot deformity. According to the types of malunion, fascio-cutaneous flap, osteotomy, joint arthrodesis or realignment was used to correct the deformity. Patients were assessed before surgery and at 12 and 24 months postoperation.

Of the 24 patients identified, six had Lisfranc joint injuries, nine had Lisfranc joint complex injuries combined with cuboid compression fractures and nine had Lisfranc joint complex injuries combined with navicular fractures. Overall, eight patients presented with poor soft tissue and massive scar at the dorsal foot. Visual analogue scale and American Orthopaedic Foot and Ankle Society midfoot scores significantly improved over the 24-month study period. At the end of the study, 21 of 24 patients (87.5%) rated their functional outcome as excellent or good.

The classification of the midfoot malunion evaluated in this study may be helpful in the decision making process for surgical intervention.

To analyze the incidence and age and gender profiles of hyperplasia in individual cervical vertebrae.

In this retrospective study, computed tomography three-dimensional reconstruction images of cervical vertebrae from patients with neck discomfort were analyzed for the presence of hyperplasia and compared with age and gender data.

Scans from a total of 580 patients (352 males, 228 females) were analyzed. The highest incidence of hyperplasia was seen in C2 (25%), followed by C1 (23%), C6 (16%), C5 (15%), C7 (9%), C4 (8%) and C3 (4%). Patients with C2 hyperplasia were the youngest and those with C1 hyperplasia were the second youngest, while patients with C7 hyperplasia were the oldest. Of those with C2, C1 and C7 hyperplasia, males were significantly younger than females, whereas of those with C3, C4, C5 and C6 hyperplasia, females were significantly younger than males.

Hyperplasia of the cervical spine shows different age and gender profiles among the seven vertebrae. These findings may be helpful for the early recognition of cervical hyperplasia and highlight the importance of protecting the atlanto-axial joint in daily life.

A retrospective study to compare surgical parameters and postoperative pain in patients undergoing coblation tonsillectomy with or without microscopic guidance.

Data regarding duration of surgery and hospital stay, intraoperative blood loss, incidence of haemorrhage and postoperative pain scores were retrieved from the medical records of adult patients undergoing coblation tonsillectomy under direct vision or with microscopic guidance.

The incidence of secondary haemorrhage (>24 h postoperatively) was significantly lower and the duration of hospital stay was significantly shorter in the microscope group (n = 92) than the direct vision group (n = 76). Pain scores both at rest and while swallowing reached ≤3 (no significant impact on quality-of-life) significantly faster in the microscope group than the direct vision group.

Microscope-assisted coblation tonsillectomy decreases the duration of hospital stay and the incidence of postoperative secondary haemorrhage, and results in an early improvement in postoperative pain scores.

To investigate how the anatomy of variant atlas vertebra impacts on the strategy used to place pedicle screws used to treat atlantoaxial instability.

The study enrolled patients with cervical instability who had a posterior arch pedicle height <3.5 mm at the anchor point, a vertebral artery groove height <3.5 mm, or both. Pedicle screws were fitted according to the anatomy of the variant atlas vertebra. Patients were followed-up to evaluate accuracy of the screw placement and maintenance of cervical stability.

A total of 28 patients were enrolled. The mean height of the atlas pedicle proximal section was >5.0 mm. For the vertebral artery groove, the height of the lateral region was significantly greater than that of the medial region. Approximately 60% of atlas vertebrae had lateral heights >3.5 mm (34 of 56). The majority of the posterior arch heights were <3.0 mm. There were no perioperative or postoperative complications observed.

Pedicle screw placement in the lateral pedicle region is the safest and most reliable strategy to treat variant atlas pedicles.

To analyse the role of serum cartilage oligomeric matrix protein (COMP) levels in the differential diagnosis of rheumatoid arthritis (RA).

This case–control study analysed the clinical and laboratory characteristics of patients with RA and healthy control subjects. The diagnostic ability of COMP for RA was evaluated by comparing it with anti-cyclic citrullinated peptide antibody levels. The sensitivity, specificity, positive and negative predictive values were calculated.

The study enrolled 82 patients with RA and 34 healthy control subjects. The serum COMP level was significantly higher in patients with RA compared with control subjects (mean ± SD 29.51 ± 9.21 ng/ml versus 17.85 ± 5.55 ng/ml, respectively). The serum COMP level was significantly higher in patients with active RA compared with patients with RA in remission (mean ± SD 33.08 ± 8.80 ng/ml versus 24.94 ± 7.65 ng/ml, respectively). The cut-off value for COMP to discriminate patients with RA from healthy individuals was 21.51 ng/ml (sensitivity 0.817, specificity 0.882, positive predictive value 0.944, negative predictive value 0.667, and accuracy 0.836).

The serum COMP level has the potential to be used as a biological marker for differentiating between patients with RA and healthy individuals.

To evaluate the anatomical safety margins in relation to thoracic epidural block by analysing magnetic resonance (MR) images.

This retrospective study identified consecutive patients who underwent MR imaging of the thoracic vertebral spine. The distance from the dura mater to the spinal cord (DTC) was measured at different thoracic intervertebral levels using three different pathways as references: the ‘U’, ‘L’ and ‘M’ lines.

A total of 346 patients provided MR images for analysis. The vertical DTC was the longest at the T5/6 intervertebral level (mean ± SD: 4.22 ± 1.43 mm) and the shortest at the T11/12 intervertebral level (mean ± SD: 2.51 ± 0.87 mm). The DTC was the longest on the ‘L’ line at the T1/2 and T5/6 intervertebral levels and on the ‘U’ line at the T10/11 intervertebral level. The difference in DTC between the ‘U’ and ‘L’ lines was the greatest at the T5/6 intervertebral level.

Differences in the DTC were observed among the thoracic intervertebral levels. The variability of the safety margin according to the angle of needle insertion was the largest at the T5/6 intervertebral level.

To investigate the effect of a standardized silicone liner programme on the duration of prosthetic rehabilitation in patients who underwent transtibial amputation as a result of peripheral arterial disease.

This retrospective study enrolled patients who underwent transtibial amputation followed by one of two stump management programmes at the same rehabilitation centre over a period of 14 years. The study compared the duration of rehabilitation following a standardized silicone liner programme compared with that following a conventional soft dressing programme.

This study included 16 patients who underwent the silicone liner programme and 11 patients who underwent the soft dressing programme. There were no significant differences between the two groups in age, sex, interval between amputation and admission to the rehabilitation centre and stump length. The duration required for the completion of the rehabilitation programme was significantly shorter for the silicone liner programme compared with the soft dressing programme (mean ± SD: 77.3 days ± 13.4 versus 125.4 days ± 66.4 days, respectively).

A standardized silicone liner programme reduced the duration of rehabilitation and could be a valuable replacement for soft dressing-based stump management.

This study evaluated the risks and outcomes of capsule retention during capsule endoscopy (CE) for investigating small bowel disease. Capsule retention is the most serious complication of CE.

Before CE, the gastrointestinal tract was evaluated for blockages with computerized tomography. Analysis of CE was made retrospectively.

Capsule endoscopy was used to investigate obscure bleeding (90.2%; n = 324) or other symptoms (9.8%; n = 35). The capsule retention rate was 11/359 (3.1%); it was retained in a malignant lesion area (adenocarcinoma or melanoma) in two patients (18.2%), in the small bowel in an ulcerated area in five patients (45.5%), and in the oesophagus/stomach in four patients (36.4%) due to dysmotility. None of the patients had symptoms of obstruction.

Scanning patients before CE did not predict capsule retention. Retention is a complication of CE, but occurs as a result of the underlying disease. The risk of retention is increased in patients with motility disorders, suspected small bowel ulcers or malignancies.