The outcome of treatment for anorexia nervosa inpatients who required urgent hospitalization

Background

This study was done to determine which psychosocial factors are related to the urgent hospitalization of anorexia nervosa patients (AN) due to extremely poor physical condition and to evaluate their outcome after inpatient treatment.

Methods

133 hospitalized AN patients were classified into an urgent hospitalization (n?=?24) or a planned hospitalization (n?=?109) group. Multiple regression analysis was done of clinical features, body mass index (BMI), psychological tests [The Minnesota Multiphasic Personality Inventory (MMPI), alexithymia, relationship with parents, and the Eating Disorder Inventory (EDI)]. The effectiveness of treatment was prospectively determined two years after discharge by the Global Clinical Score (GCS). The hospitalized weight gain and the frequency of outpatient visits were evaluated.

Results

Of the factors assessed, only BMI at admission was related to the necessity of urgent hospitalization (β?=?? 1.063, P?=?0.00). The urgent group had significantly more weight loss after discharge and poorer social adaptation on the GCS, even when the patient had a sufficient increase in body weight during inpatient treatment and an equivalent number of outpatient consultations.

Conclusion

None of the parameters of the psychosocial tests studied were significantly different between the groups. The outcome of the urgent group was poor. Two years after discharge they had difficulty maintaining weight and continued to have poor social adaptation.

     

Metabolomics approach for predicting response to neoadjuvant chemotherapy for colorectal cancer

Introduction

Colorectal cancer (CRC) is a clinically heterogeneous disease, which necessitates a variety of treatments and leads to different outcomes. Only some CRC patients will benefit from neoadjuvant chemotherapy (NACT).

Objectives

An accurate prediction of response to NACT in CRC patients would greatly facilitate optimal personalized management, which could improve their long-term survival and clinical outcomes.

Methods

In this study, plasma metabolite profiling was performed to identify potential biomarker candidates that can predict response to NACT for CRC. Metabolic profiles of plasma from non-response (n?=?30) and response (n?=?27) patients to NACT were studied using UHPLC–quadruple time-of-flight)/mass spectrometry analyses and statistical analysis methods.

Results

The concentrations of nine metabolites were significantly different when comparing response to NACT. The area under the receiver operating characteristic curve value of the potential biomarkers was up to 0.83 discriminating the non-response and response group to NACT, superior to the clinical parameters (carcinoembryonic antigen and carbohydrate antigen 199).

Conclusion

These results show promise for larger studies that could result in more personalized treatment protocols for CRC patients.

     

Periprocedural heparin bridging in patients receiving oral anticoagulation: a systematic review and meta-analysis

Background

Periprocedural heparin bridging therapy aims to reduce the risk of thromboembolic events in patients requiring an interruption in their anticoagulation therapy for the purpose of an elective procedure. The efficacy and safety of heparin bridging therapy has not been well established.

Objectives

To compare through meta-analysis the effects of heparin bridging therapy on the risk of major bleeding and thromboembolic events of clinical significance among patients taking oral anticoagulants.

Methods

We searched PubMed, EMBASE and the Cochrane library from January 2005 to July 2016. Studies were included if they reported clinical outcomes of patients receiving heparin bridging therapy during interruption of oral anticoagulant for operations. Data were pooled using random-effects modeling.

Results

A total of 25 studies, including 6 randomized controlled trials and 19 observational studies, were finally included in this analysis. Among all the 35,944 patients, 10,313 patients were assigned as heparin bridging group, and the other 25,631 patients were non-heparin bridging group. Overall, compared with patients without bridging therapy, heparin bridging therapy increased the risk of major bleeding (OR?=?3.23, 95%CI: 2.06–5.05), minor bleeding (OR?=?1.52, 95%CI: 1.06–2.18) and overall bleeding (OR?=?2.83, 95%CI: 1.86–4.30).While there was no significant difference in thromboembolic events (OR?=?0.99,95%CI: 0.49–2.00), stroke or transient ischemic attack(OR?=?1.45, 95%CI: 0.93–2.26,) or all-cause mortality (OR?=?0.71, 95%CI: 0.31–1.65).

Conclusions

Heparin-bridging therapy increased the risk of major and minor bleeding without decreasing the risk of thromboembolic events and all cause death compared to non-heparin bridging.

     

Hyper response to ovarian stimulation affects the follicular fluid metabolomic profile of women undergoing IVF similarly to polycystic ovary syndrome

Introduction

During in vitro fertilization (IVF), the hyper response to controlled ovarian stimulation (COS) is a common characteristic among patients diagnosed with polycystic ovary syndrome (PCOS), although non-diagnosed patients may also demonstrate this response.

Objectives

In an effort to investigate follicular metabolic characteristics associated with hyper response to COS, the present study analyzed follicular fluid (FF) samples from patients undergoing IVF.

Methods

FF samples were obtained from patients with PCOS and hyper response during IVF (PCOS group, N?=?15), patients without PCOS but with hyper response during IVF (HR group, N?=?44), and normo-responder patients receiving IVF (control group, N?=?22). FF samples underwent Bligh and Dyer extraction, followed by metabolomic analysis by ultra-performance liquid chromatography mass spectrometry, considering two technical replicates. Clinical data was analyzed by ANOVA and chi-square tests. The metabolomic dataset was analyzed by multivariate statistics, and the significance of biomarkers was confirmed by ANOVA.

Results

Clinical data showed differences regarding follicles production, oocyte and embryo quality. From the 15 proposed biomarkers, 14 were of increased abundance in the control group and attributed as fatty acids, diacylglycerol, triacylglycerol, ceramide, ceramide-phosphate, phosphatidylcholine, and sphingomyelin. The PCOS patients showed increased abundance of a metabolite of m/z 144.0023 that was not attributed to a class.

Conclusion

The clinical and metabolic similarities observed in the FF of hyper responders with and without PCOS diagnosis indicate common biomarkers that could assist on the development of accessory tools for assessment of IVF parameters.

     

Metabolome analysis reveals the association between the kynurenine pathway and human herpesvirus 6 encephalopathy in immunocompetent children

Introduction

Human herpesvirus 6 (HHV-6) is the second most common causative pathogen of acute encephalopathy in immunocompetent children in Japan. Identification of biomarkers associated the pathophysiology is desirable to monitor disease severity, progression, and prognosis.

Objectives

To investigate potential biomarkers for HHV-6 encephalopathy, serum metabolome profiling was analyzed and candidate metabolites were investigated the function in the diseases.

Methods

Pediatric patients with HHV-6 encephalopathy (n?=?8), febrile seizure (n?=?20), and febrile infection without febrile seizure (n?=?7) were enrolled in this study, and serum metabolites were identified and quantified. For further analysis, serum samples of HHV-6 infected patients were analyzed by absolute quantification assay for kynurenine (KYN) and quinolinic acid (QUIN) in a total of 38 patients with or without encephalopathy. An in vitro blood–brain barrier (BBB) model was used to evaluate the effect of KYN and QUIN on BBB integrity because BBB damage induces brain edema.

Results

Metabolome profiling identified 159 metabolites in serum samples. The levels of KYN and QUIN, which belong to the tryptophan-KYN pathway, were significantly higher in the HHV-6 encephalopathy group than the other two groups. When quantified in the larger patient group, remarkably high levels of KYN and QUIN were observed exclusively in the encephalopathy group. Trans-endothelial electrical resistance of the BBB model was significantly decreased after QUIN treatment in culture.

Conclusion

Metabolome analysis revealed that KYN and QUIN may be associated with the pathophysiology of HHV-6 encephalopathy. In particular, QUIN may damage BBB integrity.

     

Decreased P27 protein expression is correlated with the progression and poor prognosis of nasopharyngeal carcinoma

Background

To determine the correlation of cyclin-dependent kinase inhibitor 1B (p27) expression with clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient prognosis.

Methods

Real-time PCR and immunohistochemistry were used to examine the mRNA and protein expressions of p27 in NPC and nasopharyngeal tissues. The relationship of p27 expression levels with clinical features and prognosis of NPC patients was analyzed.

Results

The expression level of p27 mRNA was markedly lower in NPC tissues than that in the nasopharyngeal tissues (P?=?0.0006). Specific p27 protein staining by immunohistochemistry was found in the nuclei and cytoplasm of nasopharyngeal and malignant epithelial cells but decreased expression was observed in NPC samples compared to normal epithelium samples (P?=?0.002). In addition, low levels of p27 protein were inversely correlated with the status of T classification (p?=?0.002) and clinical stage (p?=?0.019) of NPC patients. Patients with lower p27 expression had a significantly shorter overall survival time than did patients with high p27 expression. Multivariate analysis suggested that the level of p27 expression was not an independent prognostic indicator (p?=?0.682) for NPC survival.

Conclusion

Low level of p27 expression is a potential unfavorable prognostic factor for patients with NPC.

Virtual slides

The virtual slide (s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1915282782109343.

     

Metabolomic prediction of endometrial cancer

Introduction

Endometrial cancer (EC) is associated with metabolic disturbances including obesity, diabetes and metabolic syndrome. Identifying metabolite biomarkers for EC detection has a crucial role in reducing morbidity and mortality.

Objective

To determine whether metabolomic based biomarkers can detect EC overall and early-stage EC.

Methods

We performed NMR and mass spectrometry based metabolomic analyses of serum in EC cases versus controls. A total of 46 early-stage (FIGO stages I–II) and 10 late-stage (FIGO stages III–IV) EC cases constituted the study group. A total of 60 unaffected control samples were used. Patients and controls were divided randomly into a discovery group (n?=?69) and an independent validation group (n?=?47). Predictive algorithms based on biomarkers and demographic characteristics were generated using logistic regression analysis.

Results

A total of 181 metabolites were evaluated. Extensive changes in metabolite levels were noted in the EC versus the control group. The combination of C14:2, phosphatidylcholine with acyl-alkyl residue sum C38:1 (PCae C38:1) and 3-hydroxybutyric acid had an area under the receiver operating characteristics curve (AUC) (95% CI)?=?0.826 (0.706–0.946) and a sensitivity?=?82.6%, and specificity?=?70.8% for EC overall. For early EC prediction: BMI, C14:2 and PC ae C40:1 had an AUC (95% CI)?=?0.819 (0.689–0.95) and a sensitivity?=?72.2% and specificity?=?79.2% in the validation group.

Conclusions

EC is characterized by significant perturbations in important cellular metabolites. Metabolites accurately detected early-stage EC cases and EC overall which could lead to the development of non-invasive biomarkers for earlier detection of EC and for monitoring disease recurrence.

     

Course of self-reported symptoms of 342 outpatients receiving medium- versus long-term psychodynamic psychotherapy

Background

The course of self-reported symptoms during medium- versus long-term psychodynamic psychotherapy has rarely been documented for outpatient settings. This observational study describes routine practice of ambulatory treatment in Germany and explores self-reported symptoms of a broad patient sample undergoing one (medium-term) versus two years (long-term) of psychodynamic psychotherapy.

Methods

Over four and a half years, longitudinal self-report symptom data were collected from 342 outpatients as part of a standardized documentation system. Self-report data were compared between patients receiving either medium-term or long-term psychodynamic psychotherapy.

Results

Routine care significantly decreased disease burden as reported by patients by small to medium effect sizes (ES) for depression (ES?=?0.58), anxiety (ES?=?0.49), obsessive-compulsive disorder (ES?=?0.54), somatoform disorder (ES?=?0.32), eating disorder (ES?=?0.38). The majority of patients completed treatment after one year and showed medium-size changes. For a subgroup of patients with depressive and/or obsessive-compulsive disorder symptoms for whom two years of therapy were deemed necessary, additional benefits were reported during the second year of treatment (ES?=?0.61 and ES??0.47, respectively).

Conclusions

Our findings suggest that both medium- and long-term psychodynamic psychotherapy decrease self-reported disease burden of patients with depression, anxiety, obsessive-compulsive, somatoform and/or eating disorders. For a subgroup of patients, additional benefits were gained in the second year of treatment.

     

Thrombus aspiration in hyperglycemic ST-elevation myocardial infarction (STEMI) patients: clinical outcomes at 1-year follow-up

Objectives

We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients.

Background

The management of hyperglycemic patients during STEMI is unclear.

Methods

We undertook an observational cohort study of 3166 first STEMI. Patients were grouped on the basis of whether they received TA or not. Moreover, among these patients we selected a subgroup of STEMI patients with hyperglycemia during the event (glycaemia?>?140 mg/dl). The endpoint at 1 year included all-cause mortality, cardiac mortality and re-hospitalization for coronary disease, heart failure and stroke.

Results

One-thousand STEMI patients undergoing PPCI to plus TA (TA-group) and 1504 STEMI patients treated with PPCI alone (no-TA group) completed the study. In overall study-population, Kaplan–Meier-analysis demonstrated no significant difference in mortality rates between patients with and without TA (P?=?0.065). After multivariate Cox-analysis (HR: 0.94, 95% CI 0.641–1.383) and the addition of propensity matching (HR: 0.86 95% CI 0.412–1.798) TA was still not associated with decreased mortality. By contrast, in hyperglycemic subgroup STEMI patients (TA-group, n?=?331; no-TA group, n?=?566), Kaplan–Meier-analysis demonstrated a significantly lower mortality (P?=?0.019) in TA-group than the no-TA group. After multivariate Cox-analysis (HR: 0.64, 95% CI 0.379–0.963) and the addition of propensity matching (HR: 0.54, 95% CI 0.294–0.984) TA was still associated with decreased mortality.

Conclusions

TA was not associated with lower mortality in PPCI for STEMI when used in our large all-comer cohort. Conversely, TA during PPCI for STEMI reduces clinical outcomes in hyperglycemic patients.Trial registration NCT02817542. 25th, June 2016

     

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

Introduction

Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.

Methods

Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.

Results

Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.

Conclusion

SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

     

<Superscript>1</Superscript>H NMR metabolic profiling of gastric cancer patients with lymph node metastasis

Introduction

Gastric cancer (GC) is a malignant tumor worldwide. As primary pathway for metastasis, the lymphatic system is an important prognostic factor for GC patients. Although the metabolic changes of gastric cancer have been investigated in extensive studies, little effort focused on the metabolic profiling of lymph node metastasis (LNM)-positive or negative GC patients.

Objectives

We performed ¹H NMR spectrum of GC tissue samples with and without LNM to identify novel potential metabolic biomarkers in the process of LNM of GC.

Methods

¹H NMR-based untargeted metabolomics approach combined with multivariate statistical analyses were used to study the metabolic profiling of tissue samples from LNM-positive GC patients (n?=?40), LNM-negative GC patients (n?=?40) and normal controls (n?=?40).

Results

There was a clear separation between GC patients and normal controls, and 33 differential metabolites were identified in the study. Moreover, GC patients were also well-classified according to LNM-positive or negative. Totally eight distinguishing metabolites were selected in the metabolic profiling of GC patients with LNM-positive or negative, suggesting the metabolic dysfunction in the process of LNM. According to further validation and analysis, especially BCAAs metabolism (leucine, isoleucine, valine), GSH and betaine may be as potential factors of diagnose and prognosis of GC patients with or without LNM.

Conclusion

To our knowledge, this is the first metabolomics study focusing on LNM of GC. The identified distinguishing metabolites showed a promising application on clinical diagnose and therapy prediction, and understanding the mechanism underlying the carcinogenesis, invasion and metastasis of GC.

     

Identification of putative biomarkers for leptomeningeal invasion in B-cell non-Hodgkin lymphoma by NMR metabolomics

Introduction

B-cell non-Hodgkin lymphoma (B-NHL) is the most common hematological malignancy and different genetic alterations are frequently detected in transformed B lymphocytes. Within this heterogeneous disease, certain aggressive subgroups have an increased risk of central nervous system (CNS) involvement at diagnosis and/or relapse, resulting in parenchymal or leptomeningeal infiltration (LI) in 5–15% of cases. The current sensitivity limitations of cerebrospinal fluid (CSF) cytology and contrast-enhanced MRI for CNS involvement, mainly at early stages, motivates the search for alternative diagnostic methods.

Objectives

Here we aim at using untargeted ¹H-NMR metabolomics to identify putative biomarkers for LI in B-NHL patients.

Methods

CSF and peripheral blood samples were obtained from B-NHL patients with a positive (n?=?7, LI group) or negative LI diagnostic (n?=?13, control group). For seven patients, CSF samples were collected during the course of intrathecal chemotherapy, making it possible to assess the patient´s response to treatment. ¹H-NMR spectra were acquired and statistical multivariate and univariate analysis were performed to identify significant alterations.

Results

Significant metabolite differences were found between LI and control groups in CSF, but not in serum. A predictive PLS-DA cross-validated model identified significant pool changes in glycine, alanine, pyruvate, acetylcarnitine, carnitine, and phenylalanine. Additionally, increments in protein signals were detected in the LI group. Significantly, the PLS-DA model predicted correctly all samples obtained from the group of patients in remission during LI treatment.

Conclusions

The results show that the CSF NMR-metabolomics approach is a promising complementary method in clinical diagnosis and treatment follow-up of LI in B-NHL patients.

     

Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: results from the ColoCare study

Background

Branched-chain amino acids (BCAA) have been previously linked to survival in colorectal cancer (CRC) patients. It is unclear whether BCAAs are prognostic biomarkers or surrogate markers for energy balance.

Objectives

We aimed to determine correlations of BCAAs with markers of energy balance over time and to investigate prognostic significance of BCAAs in CRC.

Methods

We used urinary samples from newly diagnosed CRC patients [n?=?163; (stage I–IV)] from the ColoCare study in Heidelberg, Germany, collected at surgery (n?=?163), 6 (n?=?83) and 12 months follow-up (n?=?54). Isoleucine, leucine, valine, (2Z)-3-methylglutaconic acid (3HM), 2-ethylhydracrylic acid (2EA), 2-methyl-3-hydroxybutyrate (2M3H) were detected using gas-chromatography mass-spectrometry and proton-nuclear-magnetic-resonance spectroscopy. Partial correlation coefficients between BCAAs with body mass index, physical activity (metabolic equivalent) and muscle area were computed and adjusted for sex and age at diagnosis. We used Cox proportional hazard models to investigate overall survival (OS) after 24 months of follow-up.

Results

We did not observe significant correlations between BCAAs and parameters of energy balance at all time points (correlation ranges: BMI: r?=???0.13 to ??0.01; METs: r?=???0.14 to 0.02; dorsal muscle: r?=???0.03 to 0.10). BCAAs were not associated with risk of death in stage I–III (e.g., valine: HR_log2?=?1.62, p?=?0.25) or in stage IV tumors. Elevated concentrations of 2EA and 2M3H were significantly associated with OS, independent of stage (2EA: stage I–III: HR_log2?=?0.42, p?=?0.04; stage IV: HR_log2?=?0.51, p?=?0.01).

Conclusion

Our study suggests that BCAAs in colorectal cancer patients do not reflect parameters of energy balance and may be independently associated with overall survival.

     

Feasibility of a checklist in treating hypertension in primary care – base line results from a cluster-randomised controlled trial (check and support)

Background

Most patients with antihypertensive medication do not achieve their blood pressure (BP) target. The most important factor behind this failure is poor medication adherence. However, non-adherence to therapy does not concern only patients. Clinicians also tend to lack adherence to hypertension guidelines, overestimate BP control and be satisfied with inadequate BP control. The aim of this non-blinded, cluster-randomised, controlled study was to investigate if using a checklist would improve the quality of care in the initiation of new antihypertensive medication and help reduce non-adherence.

Methods

The study was conducted in eight primary care study centres in Central Finland, randomised to function as either intervention (n?=?4) or control sites (n?=?4). We included patients aged 30–75?years who were prescribed antihypertensive medication for the first time. Initiation of medication in the intervention group was carried out with a 9-item checklist, filled in together by the treating physician and the patient. Hypertension treatment in the control group was managed by the treating physician without a study-specific protocol.

Results

In total, 119 patients were included in the study, of which 118 were included in the analysis (n?=?59 in the control group, n?=?59 in the intervention group). When initiating antihypertensive medication, an adequate BP target was set for 19% of the patients in the control group and for 68% in the intervention group. Shortly after the appointment, only 14% of the patients in the control group were able to remember the adequate BP target, compared with 32% in the intervention group. The use of the checklist was also related to more regular agreement on the next follow-up appointment (64% in the control group versus 95% in the intervention group). No adverse events or side effects were related to the intervention.

Conclusions

Even highly motivated new hypertensive patients in Finnish primary care have significant gaps in their informational and behavioural skills. The use of a checklist for initiation of antihypertensive medication was related to significant improvement in these skills. Based on our findings, the use of a checklist might be a practical tool for addressing this problem.

Trial registration

NCT02377960. Date of registration: February 26th, 2015.

     

Unbiased lipidomic profiling reveals metabolomic changes during the onset and antipsychotics treatment of schizophrenia disease

Introduction

Schizophrenia (SCH) is one of the most common psychiatric disorders, which involves impairments in motivation and cognition. The pathological mechanisms underlying SCH are still unknown, and no effective therapies can prevent or treat perfectly the cognitive impairments and deficit symptoms caused by SCH.

Objectives

We aimed to find the lipid expression change in plasma that underlie SCH onset and antipsychotics treatment.

Methods

We performed a data independent acquisition-based untargeted lipidomic approach on a quadrupole-time of flight liquid chromatography coupled to mass spectrometry platform. The plasma lipidomic profiles of SCH patients (n?=?20) pre- and post-antipsychotics treatment were acquired as well as healthy controls (n?=?29). Grouped or paired t-test were used to analyze the data.

Results

Over 1000 features were detected by our lipidomic analysis, of which 445 lipids belonging to 17 lipid species were reliably identified by tandem mass spectrometry. After statistical analysis, 47 lipids belonging to 9 lipid species were found to be dysregulated between naive SCH patients and healthy controls, and 50 lipids belonging to 9 lipid species were found to be dysregulated after antipsychotics treatment. These findings include several new SCH-relevant lipid species such as sphingomyelin, acylcarnitine and ceramide. Four types of lipid expression regulative patterns can be concluded from the above mentioned findings, revealing information about mechanism, side-effect and potential target of antipsychotics.

Conclusions

The work presented here have revealed several new lipid species which are significantly dysregulated in SCH disease development or antipsychotics treatment. These lipids provide new evidence for the pathological studies of SCH and new antipsychotics development, or can be considered as potentially candidate biomarkers for further validation.

     

Altered metabolite levels and correlations in patients with colorectal cancer and polyps detected using seemingly unrelated regression analysis

Introduction

Metabolomics technologies enable the identification of putative biomarkers for numerous diseases; however, the influence of confounding factors on metabolite levels poses a major challenge in moving forward with such metabolites for pre-clinical or clinical applications.

Objectives

To address this challenge, we analyzed metabolomics data from a colorectal cancer (CRC) study, and used seemingly unrelated regression (SUR) to account for the effects of confounding factors including gender, BMI, age, alcohol use, and smoking.

Methods

A SUR model based on 113 serum metabolites quantified using targeted mass spectrometry, identified 20 metabolites that differentiated CRC patients (n?=?36), patients with polyp (n?=?39), and healthy subjects (n?=?83). Models built using different groups of biologically related metabolites achieved improved differentiation and were significant for 26 out of 29 groups. Furthermore, the networks of correlated metabolites constructed for all groups of metabolites using the ParCorA algorithm, before or after application of the SUR model, showed significant alterations for CRC and polyp patients relative to healthy controls.

Results

The results showed that demographic covariates, such as gender, BMI, BMI², and smoking status, exhibit significant confounding effects on metabolite levels, which can be modeled effectively.

Conclusion

These results not only provide new insights into addressing the major issue of confounding effects in metabolomics analysis, but also shed light on issues related to establishing reliable biomarkers and the biological connections between them in a complex disease.

     

Hypocapnia is a biological marker for orthostatic intolerance in some patients with chronic fatigue syndrome

Context

Patients with chronic fatigue syndrome and those with orthostatic intolerance share many symptoms, yet questions exist as to whether CFS patients have physiological evidence of orthostatic intolerance.

Objective

To determine if some CFS patients have increased rates of orthostatic hypotension, hypertension, tachycardia, or hypocapnia relative to age-matched controls.

Design

Assess blood pressure, heart rate, respiratory rate, end tidal CO2 and visual analog scales for orthostatic symptoms when supine and when standing for 8 minutes without moving legs.

Setting

Referral practice and research center.

Participants

60 women and 15 men with CFS and 36 women and 4 men serving as age matched controls with analyses confined to 62 patients and 35 controls showing either normal orthostatic testing or a physiological abnormal test.

Main outcome measures

Orthostatic tachycardia; orthostatic hypotension; orthostatic hypertension; orthostatic hypocapnia or combinations thereof.

Results

CFS patients had higher rates of abnormal tests than controls (53% vs 20%, p < .002), but rates of orthostatic tachycardia, orthostatic hypotension, and orthostatic hypertension did not differ significantly between patients and controls (11.3% vs 5.7%, 6.5% vs 2.9%, 19.4% vs 11.4%, respectively). In contrast, rates of orthostatic hypocapnia were significantly higher in CFS than in controls (20.6% vs 2.9%, p < .02). This CFS group reported significantly more feelings of illness and shortness of breath than either controls or CFS patients with normal physiological tests.

Conclusion

A substantial number of CFS patients have orthostatic intolerance in the form of orthostatic hypocapnia. This allows subgrouping of patients with CFS and thus reduces patient pool heterogeneity engendered by use of a clinical case definition.

     

Discrimination of pancreatic cancer and pancreatitis by LC-MS metabolomics

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is the fifth most common cause of cancer-related death in Europe with a 5-year survival rate of <5%. Chronic pancreatitis (CP) is a risk factor for PDAC development, but in the majority of cases malignancy is discovered too late for curative treatment. There is at present no reliable diagnostic marker for PDAC available.

Objectives

The aim of the study was to identify single blood-based metabolites or a panel of metabolites discriminating PDAC and CP using liquid chromatography-mass spectrometry (LC-MS).

Methods

A discovery cohort comprising PDAC (n?=?44) and CP (n?=?23) samples was analyzed by LC-MS followed by univariate (Student’s t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Discriminative metabolite features were subject to raw data examination and identification to ensure high feature quality. Their discriminatory power was then confirmed in an independent validation cohort including PDAC (n?=?20) and CP (n?=?31) samples.

Results

Glycocholic acid, N-palmitoyl glutamic acid and hexanoylcarnitine were identified as single markers discriminating PDAC and CP by univariate analysis. OPLS-DA resulted in a panel of five metabolites including the aforementioned three metabolites as well as phenylacetylglutamine (PAGN) and chenodeoxyglycocholate.

Conclusion

Using LC-MS-based metabolomics we identified three single metabolites and a five-metabolite panel discriminating PDAC and CP in two independent cohorts. Although further study is needed in larger cohorts, the metabolites identified are potentially of use in PDAC diagnostics.

     

Effects of <Emphasis Type="Italic">ADIPOQ</Emphasis> polymorphisms on PCOS risk: a meta-analysis

Background

Whether adiponectin (ADIPOQ) polymorphisms are associated with the risk of polycystic ovary syndrome (PCOS) remain controversial. Therefore, we performed this study to better explore correlations between ADIPOQ polymorphisms and PCOS risk.

Methods

Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.

Results

Eighteen studies were enrolled for analyses. Pooled overall analyses showed that rs1501299 polymorphism was significantly associated with PCOS risk (recessive model: p?=?0.02, OR?=?0.77, 95%CI 0.62–0.95; allele model: p?=?0.001, OR?=?1.15, 95%CI 1.06–1.26). Further subgroup analyses according to ethnicity of participants revealed that rs1501299 and rs2241766 polymorphisms were both significantly correlated with PCOS risk in Caucasians. In addition, rs1501299 polymorphism was also significantly correlated with PCOS risk in East Asians.

Conclusions

Our findings indicated that rs1501299 and rs2241766 polymorphisms might serve as genetic biomarkers of PCOS in certain ethnicities.

     

“As du Coeur” study: a randomized controlled trial on quality of life impact and cost effectiveness of a physical activity program in patients with cardiovascular disease

Background

Physical activity programs (PAP) in patients with cardiovascular disease require evidence of cost-utility. To assess improvement in health-related quality of life (QoL) and reduction of health care consumption of patients following PAP, a randomized trial was used.

Methods

Patients from a health insurance company who had experienced coronary artery disease or moderate heart failure were invited to participate (N?=?1891). Positive responders (N?=?50) were randomly assigned to a progressively autonomous physical activity (PAPA) program or to a standard supervised physical activity (SPA) program. The SPA group had two supervised sessions per week over 5?months. PAPA group had one session per week and support to aid habit formation (written tips, exercise program, phone call). To measure health-related quality of life EQ-5D utility score were used, before intervention, 6?months (T6) and 1 year later. Health care costs were provided from reimbursement databases.

Results

Mobility, usual activities and discomfort improved significantly in both group (T6). One year later, EQ-5D utility score was improved in the PAPA group only. Total health care consumption in the intervention group decreased, from a mean of 4097 euros per year before intervention to 2877 euros per year after (p?=?0.05), compared to a health care consumption of 4087 euros and 4180 euros per year, in the total population of patients (N?=?1891) from the health insurance company. The incremental cost effectiveness ratio was 10,928 euros per QALYs.

Conclusion

A physical activity program is cost-effective in providing a better quality of life and reducing health care consumption in cardiovascular patients.

Trial registration

ISRCTN77313697, retrospectively registered on 20 November 2015.