The influence of diabetes on postoperative complications following colorectal surgery.

BACKGROUND: Diabetes mellitus has been commonly associated with poor surgical outcomes. The aim of this meta-analysis was to assess the impact of diabetes on postoperative complications following colorectal surgery. METHODS: Medline, Embase and China National Knowledge Infrastructure electronic databases were reviewed from inception until May 9th 2020. Meta-analysis of proportions and comparative meta-analysis were conducted. Studies that involved patients with diabetes mellitus having colorectal surgery, with the inclusion of patients without a history of diabetes as a control, were selected. The outcomes measured were postoperative complications. RESULTS: Fifty-five studies with a total of 666,886 patients comprising 93,173 patients with diabetes and 573,713 patients without diabetes were included. Anastomotic leak (OR 2.407; 95% CI 1.837-3.155; p < 0.001), surgical site infections (OR 1.979; 95% CI 1.636-2.394; p < 0.001), urinary complications (OR 1.687; 95% CI 1.210-2.353; p = 0.002), and hospital readmissions (OR 1.406; 95% CI 1.349-1.466; p < 0.001) were found to be significantly higher amongst patients with diabetes following colorectal surgery. The incidence of septicemia, intra-abdominal infections, mechanical failure of wound healing comprising wound dehiscence and disruption, pulmonary complications, reoperation, and 30-day mortality were not significantly increased. CONCLUSIONS: This meta-analysis and systematic review found a higher incidence of postoperative complications including anastomotic leaks and a higher re-admission rate. Risk profiling for diabetes prior to surgery and perioperative optimization for patients with diabetes is critical to improve surgical outcomes.

Colorectal resection via natural orifice specimen extraction versus conventional laparoscopic extraction: a meta-analysis with meta-regression.

BACKGROUND: Studies have shown differences in postoperative outcomes between two minimally invasive extraction methods for colorectal lesions-natural orifice specimen extraction surgery (NOSES) and conventional laparoscopic surgery (CLS). The aim of this study was to discover the major differences in NOSES and CLS to refine current practice. METHODS: Electronic databases were searched for articles comparing NOSES and CLS from inception till March 2020. Weighted mean differences (WMD) and odds ratio (OR) were estimated for continuous and dichotomous outcomes, respectively. Summary statistics were calculated using the DerSimonian and Laird random effects. RESULTS: Twenty-one studies (15 on malignant disease, 4 on benign disease, 2 on both) were included in this meta-analysis, totalling 2378 patients (1079 NOSE, 1299 CLS). NOSE was associated with decreased: intraoperative bleeding (WMD: - 10.652 ml; 95% CI: - 18.818 ml to - 2.482 ml; p < 0.001), pain score (WMD: - 1.520; 95% CI - 1.965 to - 1.076; p < 0.001), time to flatus (WMD: - 0.306 days; 95% CI: - 0.526 to - 0.085 days; p < 0.001), length of hospital stay (WMD: - 1.048 days; 95% CI: - 1.488 to - 0.609 days; p < 0.001), and total morbidity (OR: 0.548; 95% CI: 0.387 to 0.777; p = 0.001). Subgroup analyses showed significant differences between malignant and benign lesions for intraoperative bleeding (p = 0.011) and pain score (p = 0.010). Meta-regression analyses showed an association between the American Society of Anaesthesiologists (ASA) physical status classification III with pain (p = 0.03) and ASA III with time to flatus (p = 0.04). CONCLUSIONS: This meta-analysis and meta-regression demonstrated that NOSES had better postoperative outcomes compared to CLS. More comprehensive reviews should be conducted on the long-term outcomes specific to the extraction site to better inform clinical practice.

Prevalence and associated risk factors of insomnia among pregnant women in China.

BACKGROUND: Insomnia is common during pregnancy but the prevalence and risk factors of insomnia in Chinese women during pregnancy is not well studied. This study aimed to examine the prevalence of insomnia and its risk factors in Chinese women during pregnancy. METHODS: In this cross sectional study, 436 Chinese pregnant women with Insomnia Severity Index (ISI) ≥ 8 were clinically assessed using the insomnia criteria based on the combination of DSM-IV (Diagnostic and Statistical Manual-4th Edition) and ICD-10 (International Classification of Dieases, 10th Edition). Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS), Pregnancy Pressure Scale (PPS), Perceived physical discomfort level and number, Epworth Sleepiness Scale (ESS), and a general socio-demographic questionnaire were administered. RESULTS: The results showed that about 20% of the pregnant women met the strict diagnosis criteria of insomnia. Independent-samples t-test revealed that several risk factors were correlated with the group with insomnia (N = 84) compared to the group without insomnia (N = 352). Binary Logistic regression analysis found that more significant bed partner influence (OR = 1.92, 95% CI: 1.03-3.60), depressive symptoms (OR = 1.07, 95% CI: 1.00-1.14), daytime sleepiness (OR = 1.07, 95% CI: 1.01-1.14), subjective somatic discomfort (OR = 2.27, 95% CI: 1.11-4.65), kinds of somatic discomfort (OR = 1.14, 95% CI: 1.03-1.27) and later gestation (OR = 1.05, 95% CI: 1.01-1.09) were significantly associated with insomnia. CONCLUSION: In this cohort of Chinese pregnant women, about a fifth of women suffered from clinically significant insomnia. Measures to prevent the adverse effects of insomnia should be provided to pregnant women with depressive symptoms, Sleep disturbance of the bed partner, excessive daytime sleepiness and somatic discomfort, especially late in gestation.

Comparison of colonic stents, stomas and resection for obstructive left colon cancer: a meta-analysis.

BACKGROUND: Emergency surgery (ES) is the standard-of-care for left-sided obstructing colon cancer, with self-expanding metallic stents (SEMSs) and diverting colostomies (DCs) being alternative approaches. The aim of this study was to review the short- and long-term outcomes of SEMS versus ES or DC. METHODS: Embase and Medline were searched for articles comparing SEMS versus ES or DC. Primary outcomes were survival and recurrence rates. Secondary outcomes were peri- and postoperative outcomes. SEMS-specific outcomes include success and complication rates. Pooled odds ratio and 95% confidence interval were estimated with DerSimonian and Laird random effects used to account for heterogeneity. RESULTS: Thirty-three studies were included, involving 15,224 patients in 8 randomized controlled trials and 25 observational studies. There were high technical and clinical success rates for SEMS, with low rates of complications. Our meta-analysis revealed increased odds of laparoscopic surgery and anastomosis, and decreased stoma creation with SEMS compared to ES. SEMS led to fewer complications, including anastomotic leak, wound infection, ileus, myocardial infarction, and improved 90-day in-hospital mortality. There were no significant differences in 3- and 5-year overall, cancer-specific and disease-free survival. SEMS, compared to DC, led to decreased rates of stoma creation, higher rates of ileus and reoperation, and led to longer hospital stay. CONCLUSIONS: SEMS leads to better short-term outcomes but confers no survival advantage over ES. It is unclear whether SEMS has better short-term outcomes compared to DC. There is a lack of randomized trials with long-term outcomes for SEMS versus DC, hence results should be interpreted with caution.

Interleukin-6 and total antioxidant capacity levels following N-acetylcysteine and a combination nutraceutical intervention in a randomised controlled trial for bipolar disorder.

OBJECTIVE: The aims of this study were to evaluate changes in inflammatory and oxidative stress levels following treatment with N-acetylcysteine (NAC) or mitochondrial-enhancing agents (CT), and to assess the how these changes may predict and/or moderate clinical outcomes primarily the Montgomery-Åsberg Depression Rating Scale (MADRS). METHODS: This study involved secondary analysis of a placebo-controlled randomised trial (n = 163). Serum samples were collected at baseline and week 16 of the clinical trial to determine changes in Interleukin-6 (IL-6) and total antioxidant capacity (TAC) following adjunctive CT and/or NAC treatment, and to explore the predictability of the outcome or moderator effects of these markers. RESULTS: In the NAC-treated group, no difference was observed in serum IL-6 and TAC levels after 16 weeks of treatment with NAC or CT. However, results from a moderator analysis showed that in the CT group, lower IL-6 levels at baseline was a significant moderator of MADRS χ2 (df) = 4.90, p = 0.027) and Clinical Global Impression-Improvement (CGI-I, χ2 (df) = 6.28 p = 0.012). In addition, IL-6 was a non-specific but significant predictor of functioning (based on the Social and Occupational Functioning Assessment Scale (SOFAS)), indicating that individuals with higher IL-6 levels at baseline had a greater improvement on SOFAS regardless of their treatment (p = 0.023). CONCLUSION: Participants with lower IL-6 levels at baseline had a better response to the adjunctive treatment with the mitochondrial-enhancing agents in terms of improvements in MADRS and CGI-I outcomes.

Prevalence of comorbid major depressive disorder in Type 2 diabetes: a meta-analysis of comparative and epidemiological studies.

AIMS: To examine the average point prevalence of major depressive disorder in people with Type 2 diabetes and its associated factors in a comprehensive meta-analysis. METHODS: Two researchers independently conducted a systematic literature search of PubMed, EMBASE, PsycINFO and Cochrane databases. Studies reporting the prevalence of major depressive disorder in people with Type 2 diabetes were identified and analysed using a random-effects model. RESULTS: A total of 26 studies meeting the inclusion criteria were included in the study. The point prevalence of major depressive disorder was 14.5% (95% CI 7.9-25.3; I²=99.65). People with Type 2 diabetes were more likely to have major depressive disorder compared with the general population (odds ratio 1.73, 95% CI 1.38-2.16). Subgroup and meta-regression analyses showed that study site, study type, diagnostic criteria and age significantly moderated the prevalence of major depressive disorder. CONCLUSIONS: In this meta-analysis, the average point prevalence of major depressive disorder in people with Type 2 diabetes was high. Routine screening and more effective interventions should be implemented for this population.

CT imaging features of skeletal muscle metastasis.

AIM: To define the computed tomography (CT) features common in skeletal muscle metastases and their prevalence and to identify the most commonly associated primary malignancy and the most common muscle groups in which skeletal muscle metastases are found. METHODS AND MATERIALS: Institutional review board (IRB) waiver for informed consent was obtained. A retrospective review was conducted of CT examinations from a single, large, academic centre picture archiving and communication system (PACS) database, performed from August 2009 to July 2013. All 10,426 examinations and 8,524 unique patients reviewed had a confirmed diagnosis of malignancy. The CT reports were screened manually to identify disease involving the skeletal muscles. Images of the 60 initial studies identified were then reviewed. Cases that showed direct invasion of the tumour into the skeletal muscles, and follow-up studies of the same patient were excluded. The 27 included cases were classified under five distinct patterns. RESULTS: In the present study, the prevalence for skeletal muscle metastasis was 0.33% across all malignancies. The most common primary involved was breast cancer (25%). The most common pattern was focal intramuscular mass with homogeneous contrast enhancement. The most common sites of skeletal muscle metastasis were in the abdomen (43%) and thorax (33%) musculature. CONCLUSION: Breast cancer was the most commonly associated primary malignancy and a focal, homogeneously enhancing intramuscular mass was the most common presentation. Although skeletal muscle metastasis remains a rare entity, its incidence rate should increase with the increased usage of whole-body PET CT for cancer staging.

Sexual dysfunction in Chinese rural patients with schizophrenia.

BACKGROUND: Sexual dysfunction is common in patients with schizophrenia, however it is poorly studied in China, especially in primary health care institutions in rural areas. We investigated the prevalence of sexual dysfunction and its correlates including quality of life (QoL), in schizophrenia patients treated in primary care in a rural area in China. METHOD: By using a random numbers table, 21 small town primary care service centers (from 63 totally) were selected in the study. Data of 720 community-dwelling patients with schizophrenia in rural area with diagnoses according to DSM -IV or ICD-10 were collected by interviews. Data on socio-demographic and clinical characteristics including sexual dysfunction and quality of life (QoL) were collected using a standardized protocol and data collection procedure. Data were analyzed using chi-square tests, t-tests, U-tests, ANCOVA and multiple logistic regression as appropriate by SPSS 21.0.The level of significance was set at 0.05 (two-tailed). RESULTS: In this sample, sexual dysfunction was found in 71.3% of the whole sample, 82.7% of female patients and 64.5% of male patients. Multiple logistic regression analysis showed that older age (OR = 1.06, P<0.001, 95%CI: 1.04-1.09) and higher Brief Psychotic Rating Scale (negative domain) score (OR = 1.16, P = 0.01, 95%CI: 1.02-1.31) were significantly associated with sexual dysfunction. Contrary to previous findings, sexual dysfunction was not associated with quality of life after controlling for confounding variables. CONCLUSIONS: More than 2/3 of schizophrenia patients living in a rural area complained of sexual dysfunction, which was associated with older age and more negative psychotic symptoms. Primary care physicians should pay attention to sexual dysfunction during the assessment and treatment of patients with schizophrenia in rural areas in China.

Adjunctive memantine for schizophrenia: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND: Dysfunction of N-methyl-D-aspartate receptor (NMDAR) is involved in the pathophysiology of schizophrenia. A meta-analysis of randomized controlled trials (RCTs) was conducted to examine the efficacy and safety of memantine, a non-competitive NMDAR antagonist, in the treatment of schizophrenia. METHODS: Standardized/weighted mean differences (SMDs/WMDs), risk ratio (RR), and their 95% confidence intervals (CIs) were calculated and analyzed. RESULTS: Included in the meta-analysis were eight RCTs (n = 452) of 11.5 ± 2.6 weeks duration, with 229 patients on memantine (20 mg/day) and 223 patients on placebo. Adjunctive memantine outperformed placebo in the measures of Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale negative symptoms [SMD: -0.63 (95% CI -1.10 to -0.16), p = 0.009, I 2 = 77%], but not in the total, positive and general symptoms [SMD: -0.46 to -0.08 (95% CI -0.93 to 0.22), p = 0.06-0.60, I 2 = 0-74%] or the Clinical Global Impression Severity Scale [WMD: 0.04 (95% CI -0.24 to 0.32), p = 0.78]. The negative symptoms remained significant after excluding one outlying RCT [SMD: -0.41 (95% CI -0.72 to -0.11), p = 0.008, I 2 = 47%]. Compared with the placebo group, adjunctive memantine was associated with significant improvement in neurocognitive function using the Mini-Mental State Examination (MMSE) [WMD: 3.09, (95% CI 1.77-4.42), p < 0.00001, I 2 = 22%]. There was no significant difference in the discontinuation rate [RR: 1.34 (95% CI 0.76-2.37), p = 0.31, I 2 = 0%] and adverse drug reactions between the two groups. CONCLUSIONS: This meta-analysis showed that adjunctive memantine appears to be an efficacious and safe treatment for improving negative symptoms and neurocognitive performance in schizophrenia. Higher quality RCTs with larger samples are warranted to confirm these findings.

N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of adjunctive N-acetylcysteine (NAC), an antioxidant drug, in treating major depressive disorder (MDD), bipolar disorder, and schizophrenia. METHODS: The PubMed, Cochrane Library, PsycINFO, CNKI, CBM, and WanFang databases were independently searched and screened by two researchers. Standardized mean differences (SMDs), risk ratios, and their 95% confidence intervals (CIs) were computed. RESULTS: Six RCTs (n = 701) of NAC for schizophrenia (three RCTs, n = 307), bipolar disorder (two RCTs, n = 125), and MDD (one RCT, n = 269) were identified and analyzed as separate groups. Adjunctive NAC significantly improved total psychopathology (SMD = -0.74, 95% CI: -1.43, -0.06; I2 = 84%, P = 0.03) in schizophrenia, but it had no significant effect on depressive and manic symptoms as assessed by the Young Mania Rating Scale in bipolar disorder and only a small effect on major depressive symptoms. Adverse drug reactions to NAC and discontinuation rates between the NAC and control groups were similar across the three disorders. CONCLUSIONS: Adjunctive NAC appears to be a safe treatment that has efficacy for schizophrenia, but not for bipolar disorder or MDD. Further higher quality RCTs are warranted to determine the role of adjunctive NAC in the treatment of major psychiatric disorders.

The lymph node ratio does not provide additional prognostic information compared with the N1/N2 classification in Stage III colon cancer.

AIM: The ratio of positive nodes to total nodes, the lymph node ratio (LNR), is a proposed alternative to the current N1/N2 classification of nodal disease. The true clinical benefit of adopting the LNR, however, has not been definitively demonstrated. This study compared the LNR with the current N1/N2 classification of Stage III colon cancer. METHOD: Patients with Stage III colon cancer were identified from a prospectively maintained database (1996-2012). The specificity and sensitivity of the N1/N2 classification in the prediction of overall survival were determined using R. A cut-off point for the LNR was determined by setting the specificity the same as for the N1/N2 classification. The sensitivity of the two methods was then compared, and bootstrapping 1000-fold was performed. This was then repeated for disease-specific survival. RESULTS: The specificity and sensitivity of the N1/N2 classification in predicting 3-year overall survival in this cohort (n = 402) was 62.2% and 52.1%, respectively. The cut-off point for the LNR was determined to be 0.27 for these data. On comparing LNR with the N1/N2 classification showed that for a given specificity, the LNR did not provide a statistically significant improvement in sensitivity (52.8% vs 52.1%, P = 0.31). For disease-specific death at 3 years, the specificity and sensitivity were 60.8% and 54.6%, respectively. The LNR did not provide a statistically significant improvement (55.4% vs 54.6%, P = 0.44). CONCLUSION: Both the N1/N2 system and the LNR predict survival in colon cancer, but both have low specificity and sensitivity. The LNR does not provide additional prognostic value to current staging for overall or disease-specific survival for a given cut-off point.

A Prospective Study of Serotonin and Norepinephrine Transporter Genes and the Response to Desvenlafaxine Over 8 Weeks in Major Depressive Disorder.

No studies to date have evaluated SLC6A2 and SLC6A4 genetic polymorphisms influencing antidepressant response to desvenlafaxine. We conducted an 8-week, open-label, prospective pilot study in 35 patients with major depressive disorder to assess the effects of genetic variations in SLC6A2 and SLC6A4 on both efficacy and side effect profile of desvenlafaxine. Results revealed that homozygotes for the SLC6A4 HTTLPR S allele showed a 33% HDRS reduction compared to a 58% reduction for L allele carriers (p=0.037). No results survived adjustments for covariates or multiple comparisons. While these results need to be interpreted cautiously, they provide preliminary support for the SLC6A4 HTTLPR polymorphism as potential modifier of desvenlafaxine efficacy.

Extract of Ginkgo biloba for Tardive Dyskinesia: Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: Free radicals may be involved in the pathogenesis of tardive dyskinesia (TD). We conducted this meta-analysis to systematically examine the efficacy of extract of Ginkgo biloba (EGb), a potent antioxidant possessing free radical-scavenging properties, as a treatment for TD in schizophrenia using randomized controlled trial (RCT) data. METHOD: Drawn from English and Chinese databases, 3 RCTs of EGb augmentation of antipsychotics (APs) vs. AP plus placebo or AP monotherapy were identified. 2 evaluators extracted data. The primary outcome measure was the severity of TD symptoms assessed by the Abnormal Involuntary Movement Scale (AIMS). Weighted mean difference (WMD) and risk ratio (RR) ±95% confidence intervals (CI) were calculated. Statistical analyses were performed using Review Manager (version 5.1.7.0) and STATA (version 12.0). RESULTS: The 3 RCTs (n=299) from China, of 12 weeks duration, involved schizophrenia patients with TD of 55.9±13.4 years old. EGb (240 mg/day) outperformed the control group in reducing the severity of TD and clinical symptoms as measured by the AIMS (trials=3, n=299, WMD: -2.30 (95%CI: - 3.04, -1.55), P<0.00001) and the adverse drug reactions as assessed by the Treatment Emergent Symptom Scale (TESS) (trials=2, n=142, WMD: -2.38 (95%CI: -4.01, -0.74), P=0.004). Both the Positive and Negative Syndrome Scale (PANSS) total score (trials=2, n=239, P=0.87) and all-cause discontinuation (trials=3, n=299, P=0.21) were similar between the EGb and control group. CONCLUSION: This meta-analysis suggests that adjunctive EGb appeared to be an effective and safe option for improving TD in the treatment of schizophrenia patients. However, better RCTs are needed to demonstrate its efficacy and safety especially on cognitive function in TD. PROSPERO: CRD42015024930.

Is S-Adenosyl Methionine (SAMe) for Depression Only Effective in Males? A Re-Analysis of Data from a Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to examine whether gender differences may have affected treatment response to S-adenosyl methionine (SAMe) in a recent failed randomized clinical trial (RCT) for adults with major depressive disorder. METHODS: Data from a 2-site, 12-week, double-blind RCT (n=189) assessing the efficacy of SAMe vs. placebo and a comparator selective serotonin reuptake inhibitor (escitalopram) were subjected to post-hoc analyses to evaluate effects of patient gender on treatment response. RESULTS: When assessing the efficacy outcomes within each gender separately, SAMe was superior to placebo among males (n=51), but not among females (n=62). Males showed a significant reduction of depression severity from baseline to study endpoint on the 17-item Hamilton Depression Rating Scale (4.3 point difference; p=0.034; d=0.95), while females did not show significant change. This finding emerged despite equivalence on baseline measures of depression severity between the gender groups. CONCLUSION: RESULTS of this secondary data analysis suggest that gender might impact the antidepressant efficacy of SAMe, with greater therapeutic effect found in males. The underlying mechanism is still relatively unknown. Further work is needed to replicate this observation in independent samples.Clinicaltrials.gov identifier: NCT00101452.

Clozapine prescription and quality of life in Chinese patients with schizophrenia treated in primary care.

OBJECTIVE: Clozapine is frequently used to treat schizophrenia in China. Maintenance treatment for clinically stable patients with schizophrenia is usually provided by Chinese primary care physicians, but no study has investigated the frequency of its use prescribed by primary care physicians. This study described the frequency, demographic and clinical characteristics of clozapine treatment and its impact on insight and quality of life (QOL) of patients with schizophrenia treated in primary care in China. METHOD: A total of 623 patients with schizophrenia treated in 22 primary care services in Guangzhou, China in 2013 formed the study sample. Patients' socio-demographic and clinical characteristics including psychopathology, medication side effects and QOL were recorded using a standardized protocol and data collection. RESULTS: The frequency of clozapine prescription was 35.6% with a mean daily dose of 127.7±88.2 mg. There were no significant differences between the patients with and without clozapine in either of the QOL domains after controlling the confounding factors. Multiple logistic regression analyses revealed that patients on clozapine had younger age of onset, more hospitalizations, more severe extrapyramidal side effects, but better insight and fewer prescriptions of first generation antipsychotics. CONCLUSIONS: Clozapine use was found to be common and associated with better insight in patients with schizophrenia treated in primary care in China. Further examination of the rationale and appropriateness of clozapine in primary care in China is warranted.

Differential expression of Toll-like receptor 4 in healthy and diseased human gingiva.

BACKGROUND AND OBJECTIVE: Lipopolysaccharide (LPS)-mediated signaling in host cells involves Toll-like receptor 4 (TLR4) accessory molecules, including LPS-binding protein (LBP), cluster of differentiation 14 (CD14) and lymphocyte antigen 96 (MD-2). However, expression of these innate defense molecules in various compartments of the human periodontium is unclear. The aim of this study was to investigate the expression profile of TLR4 in human gingiva. MATERIAL AND METHODS: Human gingival biopsies were collected from healthy gingival or chronic periodontitis tissue. Primary gingival keratinocytes and fibroblasts were cultured. Immunohistochemical analysis for TLR4 was performed. Transcripts of TLR4, MD-2, CD14 and LBP, and their protein products, were examined using RT-PCR, immunoprecipitation and immunoblotting. The interactions between these molecules in keratinocytes and fibroblasts were investigated by co-immunoprecipitation. RESULTS: TLR4 immunoreactivity was found in healthy gingival epithelium and periodontitis tissue, and appeared to be lower in junctional epithelium ( p ≤ 0.01). Fibroblasts and inflammatory cells stained more strongly for TLR4 in diseased periodontal tissues (p < 0.001). Three TLR4 splicing variants, two MD-2 splicing variants and one CD14 mRNA were expressed by gingival keratinocytes and fibroblasts. Expression of TLR4, CD14 and MD-2 proteins was detected in keratinocytes and fibroblasts in vitro. TLR4 protein from gingival keratinocytes and fibroblasts could be co-immunoprecipitated with CD14 or MD-2, suggesting an association between the related molecules in vivo. LBP transcript was detected in gingival biopsies, but not in primary cultures of gingival keratinocytes or fibroblasts. CONCLUSION: TLR4, CD14 and MD-2, but not LBP, are expressed in human gingival keratinocytes and fibroblasts. The TLR4 expression level in the junctional epithelium appeared to be lowest within the periodontal epithelial barrier.

Incidence of chemotherapy-induced ovarian failure in premenopausal women undergoing chemotherapy for breast cancer.

INTRODUCTION: Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients. OBJECTIVE: This study's aim was to find the incidence of chemotherapy-induced ovarian failure (CIOF) and reversible amenorrhea in premenopausal non-metastatic breast cancer patients. METHOD: This mixed retrospective and prospective study follows premenopausal breast cancer patients receiving chemotherapy between 2008 and 2012. Patients in the prospective arm were followed up with menstrual history and serum ovarian hormones (follicle-stimulating hormone [FSH] and estradiol) until 1 year post-chemotherapy, and patients in the retrospective arm were contacted for their menstrual history. RESULTS: The mean age of the 102 subjects was 43.3 years. Of the patients, 93.1 and 77.9 % were amenorrheic at completion of chemotherapy and at 12 months post-chemotherapy, respectively. Of those who developed amenorrhea, 24.6 % regained menstruation, on average after 7.86 (range 1-15) months post-chemotherapy. Age was the only statistically significant risk factor. CIOF and reversible amenorrhea was 57 and 50 % at <35 years, 95 and 31.6 % at 35-45 years, and 97.9 and 14.9 % at >50 years, respectively. The 33 prospective patients' estradiol and FSH levels seem to correlate well with onset of amenorrhea, with a falling estradiol and rising FSH trend. Tamoxifen use was associated with elevated estradiol levels 1 year post-chemotherapy. CONCLUSION: This study found a high incidence of CIOF, with a relatively low rate of reversible amenorrhea. Premenopausal patients should be counselled prior to treatment and education and support provided.

Inflammation and endometrial bleeding.

Most of the key physiological processes in the human reproductive tract involve a significant inflammatory component. These processes include follicle development, ovulation, implantation, pregnancy, labor, postpartum, remodeling and menstruation. In this context, the term 'inflammation' usually means an influx of leukocytes ('immune cells'), often of different types, into a reproductive tract tissue. These examples of inflammation are not overtly associated with any infective process. There may also be evidence that these invading leukocytes have altered their functions to take on specific and relevant local regulatory roles. Specific sequential changes in different leukocytes can be demonstrated within human endometrium during the different phases of the normal menstrual cycle. Leukocytes are fairly sparse in numbers through the proliferative phase, but increase substantially into and through the secretory phase, so much so that around 40% of all stromal cells in the premenstrual phase are leukocytes, mainly uterine natural killer cells, a large granulated lymphocyte. Other leukocytes which play key roles in menstruation appear to be macrophages, mast cells, dendritic cells, neutrophils, eosinophils and regulatory T cells. Premenstrual withdrawal of progesterone increases the endometrial expression of inflammatory mediators, including IL-8 and MCP-1, which are believed to drive endometrial leukocyte recruitment at this time. Macrophages and neutrophils are rich sources of defensins and whey acid protein motif proteins, which play important roles in ensuring microbial protection while the epithelial barrier is disrupted. Mast cells are increasingly activated as the menstrual phase approaches, and leukocyte proteases trigger a cascade of matrix metalloproteinases and degradation of extracellular matrix. Dendritic cells and other antigen-presenting cells (e.g. macrophages) almost certainly facilitate clearance of cellular debris from the uterine cavity, and reduce the amount of viable cellular material transiting the Fallopian tubes. All of these processes are influenced or controlled by regulatory T cells. Many of these leukocytes also have the potential to release regulatory molecules which stimulate endometrial repair mechanisms. Increasing recent evidence also implicates disturbances of immune cells and their cytokine mediators in contributing to symptoms of abnormal uterine bleeding and pelvic pain. These recent findings all point towards the importance of the 'inflammatory process' in both normal and abnormal endometrial bleeding.