Predictors Of Poor Long-term Outcome Research Articles

Genetic and peripheral biomarkers of comorbid posttraumatic stress disorder and traumatic brain injury: a systematic review

BackgroundPosttraumatic stress disorder (PTSD) commonly cooccurs with traumatic brain injury (TBI) in military populations and is a significant predictor of poor long-term outcomes; however, it is unclear to what extent specific biological variables are associated with comorbidity. This PROSPERO-registered systematic review evaluates the current body of literature on genetic and peripheral biomarkers associated with comorbid TBI and PTSD.MethodsSearches were conducted in four databases (PubMed, PsycInfo, PTSDPubs, Scopus). We included published studies examining differences in peripheral biomarkers among civilian, military, and veteran participants with both TBI and PTSD compared to those with TBI alone as well as, in some cases, PTSD alone and healthy controls. Data were extracted from included studies and evidence quality was assessed.ResultsOur final analysis included 16 studies, the majority of which were based on data from active duty military and veteran participants. The results suggest that multiple gene variants are likely to contribute to the cumulative risk of PTSD comorbid with TBI. An elevated circulating level of the pro-inflammatory cytokine IL-6 was the most consistently replicated blood-based indicator of comorbid illness, compared to mTBI alone.ConclusionSeveral genetic and protein markers of cellular injury and inflammation appear to be promising indicators of chronic pathology in comorbid TBI and PTSD. Additional research is needed to determine how such factors indicate, predict, and contribute to comorbidity and to what extent they represent viable targets for the development of novel diagnostic tools and therapeutic interventions.

Residual HCV-RNA and Elevated Platelet-to-Lymphocyte Ratio Predict Poor Long-Term Outcomes in Patients with Chronic HepatitisC After Treatment.

Despite achieving sustained viral response (SVR) after treatment with direct-acting antivirals (DAAs), the risk of liver disease progression and extrahepatic complications in chronic hepatitisC (CHC) remains. We aimed to determine the role of residual HCV-RNA in peripheral blood mononuclear cells (PBMCs), a condition known as occult hepatitis C (OCI), and systemic inflammatory markers as predictors of long-term outcomes in patients treated with DAAs. We followed 42 patients treated with DAAs with OCI status determined after therapy, for a median of 6.3years. Plasma levels of 16 cytokines and chemokines were measured in samples collected 12-15months after end of treatment. Samples from 10 patients with CHC and 8healthy controls were used for comparison. The presence of HCV-RNA in PBMCs correlated with adverse outcomes [odds ratio (OR) 17.6, confidence interval (CI) 1.8-175); p = 0.011], and an elevated platelet-to-lymphocyte ratio (PLR) was associated with mortality. Patients with residual HCV-RNA had higher levels of macrophage-derived chemokine (MDC/CCL22) (p = 0.026) and interleukin-18 (IL-18) (p = 0.009), but lower levels of fractalkine/CX3CL1 (p = 0.007), interferon gamma (IFNγ) (p = 0.016), IL-13 (p = 0.009), and lymphotoxin alpha (LTα) (p = 0.007) compared to those without OCI. The profile of immune mediators in patients with OCI differed more from healthy controls than from patients without OCI. These findings suggest that residual HCV-RNA and elevated PLR are potential predictors of poor long-term outcomes in patients treated with DAAs, possibly linked to an altered cytokine/chemokine response.

Quantification of blood and CSF volume to predict outcome after aneurysmal subarachnoid hemorrhage

This study aimed to describe the relationship between blood and CSF volumes in different compartments on baseline CT after aSAH, assess if they independently predict long-term outcome, and explore their interaction with age. CT scans from patients participating in a prospective multicenter randomized controlled trial of patients with aSAH were segmented for blood and CSF volumes. The primary outcomes were the mRS, and the Subarachnoid Hemorrhage Outcome Tool (SAHOT) at day 28 and 180. Univariate regressions were conducted to identify significant predictors of poor outcomes, followed by principal component analysis to explore correlations between imaging variables and WFNS. A multivariate predictive model was then developed and optimized using stepwise regression. CT scans from 97 patients with a median delay from symptom onset of 271 min (131–547) were analyzed. Univariate analysis showed only WFNS, and total blood volume (TBV) were significant predictors of both short and long-term outcome with WFNS more predictive of mRS and TBV more predictive of SAHOT. Principal component analysis showed strong dependencies between the imaging predictors. Multivariate ordinal regression showed models with WFNS alone were most predictive of day 180 mRS and models with TBV alone were most predictive of SAHOT. TBV was the most significant measured imaging predictor of poor long-term outcome after aSAH. All these imaging predictors are correlated, however, and may have multiple complex interactions necessitating larger datasets to detect if they provide any additional predictive value for long-term outcome.

Genophenotypic correlates and long-term outcome prognosticators of left ventricular non-compaction in children

BackgroundTo investigate the outcomes, clinical prognosticators, and genetic profiles of pediatric left ventricular non-compaction (LVNC). MethodsAll subjects were <18 years old, diagnosed with LVNC between January 2008 and December 2020. Whole-exome sequencing was undertaken. The primary endpoint was composite outcome, including death, heart transplant, and left ventricular assist device implantation. ResultsThirty-three patients were enrolled, males predominating (57.6%). Median age at diagnosis was 0.33 (0.1–7.2) years. Family history was documented in four (12.1%). Five (15.2%) had sustained arrhythmias. Mean follow-up period was 9.5 years, and 5- and 10-year event-free survival were 84.8% and 66.9%, respectively. Seven died of heart failure, four received heart transplants, and one required left ventricular assist device placement. Log of baseline NT-proBNP (adjusted odds ratio [aOR] = 4.4, p = 0.012) and lack of improvement in NT-proBNP (aOR = 41.2, p = 0.033) impacted the primary outcome most significantly. Eighteen out of 25 genetic testing (72%) revealed chromosomal anomalies, or pathogenic or likely pathogenic variants. Three genetic variants (PLEKHM2 p.G419R, RYR2 p.V2571A, and SCN5A p.M1676I) were significantly associated with the primary outcome (p = 1.52 × 10−6). ConclusionsPediatric LVNC is a rare disorder with variable genetic underpinnings. Baseline NT-proBNP values and lack of improvement in NT-proBNP levels were important predictors of poor long-term outcomes. Pathogenic genetic variants or chromosomal anomalies are not unusual.

Cerebral hypoperfusion exacerbates vascular dysfunction after traumatic brain injury

Traumatic brain injuries are extremely common, and although most patients recover from their injuries many TBI patients suffer prolonged symptoms and remain at a higher risk for developing cardiovascular disease and neurodegeneration. Moreover, it remains challenging to identify predictors of poor long-term outcomes. Here, we tested the hypothesis that preexisting cerebrovascular impairment exacerbates metabolic and vascular dysfunction and leads to worse outcomes after TBI. Male mice underwent a mild surgical reduction in cerebral blood flow using a model of bilateral carotid artery stenosis (BCAS) wherein steel microcoils were implanted around the carotid arteries. Then, 30 days post coil implantation, mice underwent TBI or sham surgery. Gene expression profiles, cerebral blood flow, metabolic function, oxidative damage, vascular health and angiogenesis were assessed. Single nuclei RNA sequencing of endothelial cells isolated from mice after TBI showed differential gene expression profiles after TBI and BCAS, that were further altered when mice underwent both challenges. TBI but not BCAS increased mitochondrial oxidative metabolism. Both BCAS and TBI decreased cerebrovascular responses to repeated whisker stimulation. BCAS induced oxidative damage and inflammation in the vasculature as well as loss of vascular density, and reduced the numbers of angiogenic tip cells. Finally, intravascular protein accumulation was increased among mice that experienced both BCAS and TBI. Overall, our findings reveal that a prior vascular impairment significantly alters the profile of vascular health and function of the cerebrovasculature, and when combined with TBI may result in worsened outcomes.

Predictors of poor functional outcomes in adults with type I Chiari Malformation: Clinical and surgical factors assessed with the Chicago Chiari Outcome Scale over long-term follow-up

ObjectiveThis study aimed to identify clinical and surgical features associated with poor long-term postoperative outcomes in patients diagnosed with Type I Chiari Malformation (CMI) treated with posterior fossa decompression with duroplasty (PFDD), with or without tonsillar coagulation. MethodsThis retrospective, single-center study included 107 adult patients with CMI surgically treated between 2010 and 2021. The surgical technique involved a midline suboccipital craniectomy, C1 laminectomy, durotomy, arachnoid dissection, duroplasty, and tonsillar coagulation until 2014, after which tonsillar coagulation was discontinued. Postoperative outcomes were assessed using the Chicago Chiari Outcome Scale (CCOS) at a median follow-up of 35 months. Clinical, surgical, and neuroimaging data were analyzed using the Wilcoxon signed-rank test, Cox regression analysis, and Kaplan-Meier survival curves to identify predictors of poor functional outcomes. ResultsOf the 107 patients (mean age 43.9 years, SD 13), 81 (75.5 %) showed functional improvement, 25 (23.4 %) remained unchanged, and 1 (0.9 %) experienced worsened outcomes. Cephalalgia, bilateral motor weakness, and bilateral paresthesia were the most frequent initial symptoms. Tonsillar coagulation was performed in 31 cases (28.9 %) but was clinically associated with higher rates of unfavorable outcomes. The Wilcoxon signed-rank test indicated that long-term follow-up CCOS was significantly higher than postoperative CCOS (Z = −7.678, p < 0.000). Multivariate Cox analysis identified preoperative bilateral motor weakness (HR 6.1, 95 % CI 1.9–18.9; p = 0.002), hydrocephalus (HR 3.01, 95 % CI 1.3–6.9; p = 0.008), and unilateral motor weakness (HR 2.99, 95 % CI 1.1–8.2; p = 0.033) as significant predictors of poor outcomes on a long-term follow-up. ConclusionThis study highlights the high rate of functional improvement in CMI patients following PFDD. Preoperative motor weakness and hydrocephalus were significant predictors of poor long-term outcomes. Tonsillar coagulation did not demonstrate a clear clinical benefit and may be associated with worse outcomes. Our findings suggest that careful preoperative assessment and selection of surgical techniques are crucial for optimizing patient outcomes.

Long-term functional outcomes in polytrauma: a fundamentally new approach is needed in prediction

PurposeModern trauma care has reduced mortality but poor long-term outcomes with low follow-up rates are common with limited recommendations for improvements. The aim of this study was to describe the impact of severe injury on the health-related quality of life, specifically characterise the non-responder population and to identify modifiable predictors of poorer outcomes.MethodsFive-year (2012–2016) prospective cohort study was performed at a level 1 trauma centre. Baseline Short-Form Health Survey (SF36) was collected at admission, and at 6 and 12 months postinjury together with demographics, injury mechanism and severity, psychosocial wellbeing, and return to work capacity.ResultsOf the 306 consecutive patients [age 52 ± 17 years, male 72%, ISS 21 (17, 29), mortality 5%], 195 (64%) completed questionnaires at baseline, and at 12 months. Preinjury physical health scores were above the general population (53.1 vs. 50.3, p < 0.001) and mental health component was consistent with the population norms (51.7 vs. 52.9, p = 0.065). One year following injury, both physical health (13.2, 95% CI 14.8, 11.6) and mental health scores (6.0, 95% CI 8.1, 3.8) were significantly below age- and sex-adjusted preinjury baselines. Non-responders had similar ISS but with a lower admission GCS, and were more likely to be younger, and without comorbidities, employment, or university education.ConclusionContrary to their better than population norm preinjury health status, polytrauma patients remain functionally impaired at least 1 year after injury. The identified high risk for non-responding group needs more focused efforts for follow-up. A fundamentally different approach is required in polytrauma research which identify modifiable predictors of poor long-term outcomes.

En Bloc Resection for Spinal Cord Hemangioblastomas: Surgical Technique and Clinical Outcomes.

Spinal cord hemangioblastomas are rare benign and highly vascular tumors that develop either sporadically or as part of von Hippel-Lindau (VHL) disease. Generally, complete resection without significant neurologic deficit remains considerably challenging due to the risk of massive bleeding. The current study therefore aimed to describe en bloc resection of spinal cord hemangioblastomas according to the typical anatomical structures of peripheral lesions and evaluate the neurofunctional prognosis of this technique. A total of 39 spinal cord hemangioblastomas from a series of 19 patients who underwent en bloc resection were retrospectively analyzed. In all cases, clinical and radiologic characteristics, as well as surgical tenets, were retrospectively determined and analyzed. Short- and long-term outcomes were analyzed using the McCormick grade and Odom's criteria. Factors significantly associated with poor neurologic function after en bloc resection were also determined. All 39 spinal cord hemangioblastomas, including 28 intramedullary, 2 intramedullary-extramedullary, and 9 extramedullary lesions, were located dorsally or dorsolaterally (100.0%). The most common lesion location was the thoracic segment (53.8%), with most of the lesions being accompanied by syringomyelia (94.7%). Long-term follow-up (mean: 103 ± 50.4 months) for prognosis determination revealed that 88.2% (15/17) of all cases had stable or improved neurofunctional outcomes according to the McCormick grade and Odom's criteria. Only one case with VHL disease developed recurrence 4 years after surgery. Additionally, statistical analysis showed that VHL disease was an independent prognostic factor associated with deteriorating neurologic function (p = 0.015). En bloc resection facilitated satisfactory long-term functional outcomes in patients with spinal cord hemangioblastomas. Given that VHL disease was identified as a predictor of poor long-term outcomes, regular long-term follow-up of patients with VHL-associated spinal cord hemangioblastoma seems necessary.

Post-Stroke Depression: Prevalence, Associated Factors, and Relationship to Disability in a Tertiary Care Center in Sri Lanka.

Background and Objectives The prevalence of stroke in urban Sri Lanka is estimated at 10.4 per 1000 and is expected to rise. Post-stroke depression (PSD) is an independent predictor of poor long-term outcomes. It leads to suboptimal rehabilitation, decreased quality of life, and increased mortality and is under-recognized. The main objectives of this study were to estimate the prevalence of depression in stroke, assess factors associated with PSD, and assess the relationship of PSD to disability. Materials and Methods A descriptive cross-sectional study was conducted at the Neurology and Medical Ward, National Hospital of Sri Lanka. Non-probability, consecutive sampling was used to collect data from patients with ischemic stroke admitted from January 2019 to January 2020. Patients with significant pre-existing depression, cognitive impairment, and language deficits were excluded. A structured, pre-tested interviewer-administered questionnaire was used to assess the prevalence and associated factors of PSD. Beck's Depression Inventory (BDI) was administered 3 months following the stroke to screen for depression. Modified Rankin Score (MRS) was used to assess disability on admission, discharge, and at 3 months. Results Eighty-one stroke patients were screened. The mean age was 66.6 years (±standard deviation [SD]: 12.5). Male:female ratio was 1.2:1. Depression at 3 months of follow-up was observed in 35.8% (95% confidence interval [CI]: 25.4–47.2%) of participants. Following bivariate analysis, large vessel stroke ( p < 0.001), cortical stroke ( p < 0.001), frontal lobe lesions ( p < 0.001), history of past stroke ( p = 0.014), and sexual dysfunction ( p = 0.026) were associated with increased risk of PSD. The odds of a person with severe disability developing PSD was 7.9 times more than a person with a less severe disability at discharge from hospital and at 3 months of follow-up (odds ratio [OR] =7.9; 95% CI: 2.7–23.3, p = 0.000). Conclusions PSD occurs in one-third of strokes, keeping with previous studies. The risk of having PSD is higher among patients with severe disabilities. The difference in risk factors identified compared with previous studies can be attributable to differences in methodology. Identifying risk factors for post-stroke depression is essential to mitigate the poor outcome.

Clinical significance of tacrolimus intra-patient variability on kidney transplant outcomes according to pre-transplant immunological risk

High intra-patient variability (IPV) of tacrolimus trough concentrations is increasingly recognized as a predictor of poor long-term outcomes in kidney transplant. However, there is a lack of information regarding the association between tacrolimus IPV and graft outcomes according to immunological risk. We analyzed tacrolimus IPV using the coefficient of variability from months 6–12 after transplantation in 1080 kidney transplant recipients. Patients were divided into two immunological risk groups based on pre-transplant panel reactive antibodies and donor-specific antibodies. High immunological risk was defined as panel reactive antibodies ≥ 20% or the presence of donor-specific antibodies. The effects of tacrolimus IPV on graft outcomes were significantly different between low and high immunological risk patients. A multivariable Cox regression model confirmed that high tacrolimus IPV was an independent risk factor for graft failure in the high risk group (HR, 2.90; 95% CI, 1.42–5.95, P = 0.004). In the high risk group, high tacrolimus IPV was also significantly associated with increased risk of antibody-mediated rejection (P = 0.006). In contrast, death-censored graft survival and antibody-mediated rejection in the low immunological risk group was not significantly different by tacrolimus IPV. High tacrolimus IPV significantly increases the risk of graft failure and antibody-mediated rejection in patients with high immunological risk.

Status epilepticus without impairment of consciousness: Long-term outcomes according to duration

ObjectiveThe point after which non-convulsive status epilepticus (NCSE) can cause permanent damage remains to be elucidated. The aim of this study was to analyze the association between time to resolution and long-term outcomes in NCSE. MethodsWe performed a retrospective study of all patients with focal NCSE without consciousness impairment at two tertiary care hospitals in Spain. All the data were registered prospectively and the study period was December 2014–May 2018. We collected information on demographics, SE etiology, time to administration of different lines of treatment, time to NCSE resolution, and outcomes at discharge, 1 year, and 4 years. Clinical outcome was prospectively categorized as good (return to baseline function) or poor (new disability and death). ResultsSeventy-four patients with a mean (±SD) age of 63.4 ± 17.5 years and a mean follow-up time of 2.4 ± 2.2 years were studied. A poor outcome at discharge was associated with a potentially fatal etiology (p < 0.001), EMSE score (Epidemiology-based Mortality Score in Status Epilepticus) (p = 0.012), lateral periodic discharges on EEG (p = 0.034), and occurrence of major complications during hospitalization (p = 0.007). An SE duration of >100 h was clearly associated with a worse outcome (p < 0.001). In the multiple regression analysis, the only independent predictors of a poor outcome at discharge were an SE duration of >+100 hours (p = 0.001), a potentially fatal etiology (p = 0.001), and complications during hospitalization (p = 0.010). An SE duration of >100 hours retained its value as the optimal cutoff point for predicting poor outcomes at both 1 year (p = 0.037) and 4 years (p = 0.05). Other predictors of poor long-term outcomes were a potentially fatal etiology (p < 0.001) and EMSE score (p = 0.034) at 1 year, and progressive symptomatic etiology at 4 years (p = 0.025). SignificanceIn patients with focal NCSE without consciousness impairment, a potentially fatal etiology and an SE duration of >100 h were associated with poor short-term and long-term outcomes.

The predictive value of systemic immune inflammation index for postoperative survival of gallbladder carcinoma patients.

Growing evidence indicates that systemic immune inflammation index (SII) can predict the prognosis of various solid tumors. The objective of this study aimed to investigate the efficacy of SII in predicting the prognosis of gallbladder carcinoma (GBC) patients after radical surgery. A consecutive series of 93 patients with GBC who underwent radical resection were enrolled in the retrospective study. The cutoff value for the SII was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the SII and the clinicopathologic characteristics were analyzed using Pearson's χ2 test and Fisher's exact test. Survival curves were calculated using the Kaplan-Meier method. Univariate analysis was performed to evaluate the prognostic relevance of preoperative parameters. The multivariate Cox regression proportional hazard model was used to assess variables significant on univariate analysis. The Kaplan-Meier survival analysis and the multivariate analysis of patients with GBC who received radical resection showed SII independently predicted OS. The univariate analysis showed that the TNM stage, SII, CA19-9, ALP, prealbumin, NLR, MLR, lymph node metastasis, and histopathological type were all associated with overall survival. In time-dependent ROC analysis, the area of the SII-CA19-9 under the ROC curve (AUC) was higher than that of the preoperative SII or CA19-9 levels for the prediction of OS. Our results demonstrate that high SII was a predictor of poor long-term outcomes among patients with GBC undergoing curative surgery. SII-CA19-9 classification may be more effective in predicting the postoperative prognosis of GBC patients.

Dysbiosis in a canine model of human fistulizing Crohn’s disease

ABSTRACT Crohn’s disease (CD) is a chronic immune-mediated inflammatory condition caused by the loss of mucosal tolerance toward the commensal microbiota. On average, 29.5% and 42.7% CD patients experience perianal complications at 10 and 20 y after diagnosis, respectively. Perianal CD (pCD) result in high disease burden, diminished quality of life, and elevated health-care costs. Overall pCD are predictors of poor long-term outcomes. Animal models of gut inflammation have failed to fully recapitulate the human manifestations of fistulizing CD. Here, we evaluated dogs with spontaneous canine anal furunculosis (CAF), a disease with clinical similarities to pCD, as a surrogate model for understanding the microbial contribution of human pCD pathophysiology. By comparing the gut microbiomes between dogs suffering from CAF (CAF dogs) and healthy dogs, we show CAF-dog microbiomes are either very dissimilar (dysbiotic) or similar (healthy-like), yet unique, to healthy dog’s microbiomes. Compared to healthy or healthy-like CAF microbiomes, dysbiotic CAF microbiomes showed an increased abundance of Bacteroides vulgatus and Escherichia coli and a decreased abundance of Megamonas species and Prevotella copri. Our results mirror what have been reported in previous microbiome studies of patients with CD; particularly, CAF dogs exhibited two distinct microbiome composition: dysbiotic and healthy-like, with determinant bacterial taxa such as E. coli and P. copri that overlap what it has been found on their human counterpart. Thus, our results support the use of CAF dogs as a surrogate model to advance our understanding of microbial dynamics in pCD.

The Impact of Previous Acute Decompensation on the Long-Term Prognosis of Alcoholic Hepatitis in Cirrhotic Patients.

Recurrent episodes of liver injury may either waste hepatic reserve or induce tolerance to further injury. We aimed to investigate whether the previous acute decompensation (AD) in liver cirrhosis (LC) affects the long-term transplant-free survival of patients with alcoholic hepatitis (AH). The survival data of 894 alcoholic LC cohort who had been admitted with acute deterioration in 21 academic hospitals in Korea were prospectively followed up. Enrolled patients were divided into three groups: Group 1, without AH; group 2, with nonsevere AH; and group 3, with severe AH. Although the baseline liver function was not different between the groups with or without previous AD, it was a significant predictor of poor long-term outcomes. The presence of previous AD negatively affected long-term overall survival (HR 1.62, 95% C.I. 1.20–2.18, p = 0.002) in groups 1 and 2 as a whole, independent of the Model for End-stage Liver Disease score. The three-month conditional survival was significantly worse in group 3 for up to 12 months in the presence of previous AD (p < 0.05). We concluded that not only the severity of AH, but also the prior AD is an important predictor of long-term outcomes in alcoholic LC patients with acute deterioration.

A 12-year review of patient-reported outcomes after reduction mammoplasty in patients with high body mass index.

Patients with increased body mass index (BMI) are often denied reduction mammoplasty due to concern for high morbidity. There is a paucity of evidence identifying high BMI as a predictor of poor long-term outcomes in reduction mammoplasty. In this study, we investigated the influence of BMI on long-term patient satisfaction following reduction mammoplasty.All patients undergoing reduction mammoplasty over a 12-year period at a single institution were included in the study. A retrospective chart review was conducted to extract demographics, operative data, and postoperative course including complications. Patients were classified into 4 categories based on BMI (normal (<25), overweight (25–29.9), obese (30–39.9), and morbidly obese (≥40)). Patient satisfaction was assessed using a customized survey which was administered over the phone. Only patients with complete medical records who participated in the survey were included.The 70 patients met the inclusion criteria for the study. Median time from surgery to survey was 6 years. Overall satisfaction after reduction mammoplasty was high, 5 on a 5-point Likert scale. The amount of breast tissue resected correlated with patient BMI (P <.01). There was no statistical difference in satisfaction across BMI classes. Furthermore, high BMI (obese, and morbidly obese) was not associated with higher postoperative complications (P = .70). Those with a high overall satisfaction score had a significantly greater self-reported aesthetic score compared to those with low and mid satisfied scores (P <.01).Following reduction mammoplasty, patients report high satisfaction which is sustained over several years. Obesity is not associated with a higher incidence of complications or lower satisfaction. Our data suggest that patients with a high BMI should not be denied reduction mammoplasty out of concern for higher complication rate or reduced patient satisfaction due to BMI alone, but reduction mammoplasty should be considered in the setting of overall health counseling.

Prognostic significance of neutrophil-lymphocyte ratio and carbohydrate antigen 19-9 in patients with gallbladder carcinoma.

The neutrophil–lymphocyte ratio (NLR) is an immune response-related indicator and it is associated with poor prognosis of various cancers. The carbohydrate antigen19-9 (CA19-9) is a tumor-associated antigen and it has prognostic relevance in gallbladder carcinoma (GBC). We aimed to analyze whether preoperative NLR and serum CA19-9 were associated with outcomes of GBC patients after surgery with curative intent.Between January 2010 and May 2015, 90 resectable GBC patients who underwent curative surgery in our institution were included. All final diagnoses were confirmed by pathologic examination. The demographics, clinical, and histopathology data were analyzed. The Cox regression proportional hazard model and Kaplan–Meier method were used to assess prognostic factors.The cutoff values of 4.33 and 250.90 U/mL were defined as high NLR and high CA19-9, respectively. The univariate analyses showed that TNM stage, lymph node metastasis, the degree of tumor differentiation, margin status, combined hepatectomy, CA19-9, NLR, and PNI were all associated with overall survival (P < .05). According to the multivariable analysis, NLR (hazard ratio (HR) 3.840, 95% confidence interval (95% CI): 2.122–6.947, P < .001), CA19-9 (HR 2.230, 95% CI: 1.297–3.835, P = .004), TNM stage (HR 3.864, 95% CI: 1.819–8.207, P < .001), lymph node metastasis (HR 1.679, 95% CI: 1.005–2.805, P = .048), and margin status (HR 1.873, 95% CI: 1.063–3.300, P = .030) were independent prognostic factors. The median survival time in low NLR and CA19-9 group was better than high NLR and CA19-9 group (P < .05).The preoperative NLR and serum CA19-9 are associated with prognosis of patients with GBC. High NLR and high CA19-9 were predictors of poor long-term outcome among patients with GBC undergoing curative surgery.

Optimal primary care management of clinical osteoarthritis and joint pain in older people: a mixed-methods programme of systematic reviews, observational and qualitative studies, and randomised controlled trials

BackgroundOsteoarthritis (OA) is the most common long-term condition managed in UK general practice. However, care is suboptimal despite evidence that primary care and community-based interventions can reduce OA pain and disability.ObjectivesThe overall aim was to improve primary care management of OA and the health of patients with OA. Four parallel linked workstreams aimed to (1) develop a health economic decision model for estimating the potential for cost-effective delivery of primary care OA interventions to improve population health, (2) develop and evaluate new health-care models for delivery of core treatments and support for self-management among primary care consulters with OA, and to investigate prioritisation and implementation of OA care among the public, patients, doctors, health-care professionals and NHS trusts, (3) determine the effectiveness of strategies to optimise specific components of core OA treatment using the example of exercise and (4) investigate the effect of interventions to tackle barriers to core OA treatment, using the example of comorbid anxiety and depression in persons with OA.Data sourcesThe North Staffordshire Osteoarthritis Project database, held by Keele University, was the source of data for secondary analyses in workstream 1.MethodsWorkstream 1 used meta-analysis and synthesis of published evidence about effectiveness of primary care treatments, combined with secondary analysis of existing longitudinal population-based cohort data, to identify predictors of poor long-term outcome (prognostic factors) and design a health economic decision model to estimate cost-effectiveness of different hypothetical strategies for implementing optimal primary care for patients with OA. Workstream 2 used mixed methods to (1) develop and test a ‘model OA consultation’ for primary care health-care professionals (qualitative interviews, consensus, training and evaluation) and (2) evaluate the combined effect of a computerised ‘pop-up’ guideline for general practitioners (GPs) in the consultation and implementing the model OA consultation on practice and patient outcomes (parallel group intervention study). Workstream 3 developed and investigated in a randomised controlled trial (RCT) how to optimise the effect of exercise in persons with knee OA by tailoring it to the individual and improving adherence. Workstream 4 developed and investigated in a cluster RCT the extent to which screening patients for comorbid anxiety and depression can improve OA outcomes. Public and patient involvement included proposal development, project steering and analysis. An OA forum involved public, patient, health professional, social care and researcher representatives to debate the results and formulate proposals for wider implementation and dissemination.ResultsThis programme provides evidence (1) that economic modelling can be used in OA to extrapolate findings of cost-effectiveness beyond the short-term outcomes of clinical trials, (2) about ways of implementing support for self-management and models of optimal primary care informed by National Institute for Health and Care Excellence recommendations, including the beneficial effects of training in a model OA consultation on GP behaviour and of pop-up screens in GP consultations on the quality of prescribing, (3) against adding enhanced interventions to current effective physiotherapy-led exercise for knee OA and (4) against screening for anxiety and depression in patients with musculoskeletal pain as an addition to current best practice for OA.ConclusionsImplementation of evidence-based care for patients with OA is feasible in general practice and has an immediate impact on improving the quality of care delivered to patients. However, improved levels of quality of care, changes to current best practice physiotherapy and successful introduction of psychological screening, as achieved by this programme, did not substantially reduce patients’ pain and disability. This poses important challenges for clinical practice and OA research.LimitationsThe key limitation in this work is the lack of improvement in patient-reported pain and disability despite clear evidence of enhanced delivery of evidence-based care.Future work recommendations(1) New thinking and research is needed into the achievable and desirable long-term goals of care for people with OA, (2) continuing investigation into the resources needed to properly implement clinical guidelines for management of OA as a long-term condition, such as regular monitoring to maintain exercise and physical activity and (3) new research to identify subgroups of patients with OA as a basis for stratified primary care including (i) those with good prognosis who can self-manage with minimal investigation or specialist treatment, (ii) those who will respond to, and benefit from, specific interventions in primary care, such as physiotherapy-led exercise, and (iii) develop research into effective identification and treatment of clinically important anxiety and depression in patients with OA and into the effects of pain management on psychological outcomes in patients with OA.Trial registrationCurrent Controlled Trials ISRCTN06984617, ISRCTN93634563 and ISRCTN40721988.FundingThis project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research Programme and will be published in full inProgramme Grants for Applied Research Programme; Vol. 6, No. 4. See the NIHR Journals Library website for further project information.

Prevalence and predictors of persistent pelvic girdle pain 12\xa0years postpartum

BackgroundPelvic girdle pain (PGP) is not always a self-limiting condition. Women with more pronounced persistent PGP (PPGP) report poorer health status compared to women with less pronounced symptoms. The knowledge concerning the long-term consequences of PPGP is limited, thus more knowledge in this area is needed. The overall aim was to study the prevalence and predictors of PPGP 12 years after delivery.MethodsThis is a long-term follow-up study based on a previous cohort study that commenced in 2002. New questionnaire data 12 years postpartum were collected in 2014 and early 2015. The questionnaire was distributed to a total of 624 women from the initial cohort.ResultsIn total, 295 women (47.3%) responded to the questionnaire where 40.3% (n = 119) reported pain to a various degree and 59% (n = 174) reported no pain. Increased duration and/or persistency of pain, self-rated health, sciatica, neck and/or thoracic spinal pain, sick leave the past 12 months, treatment sought, and prescription and/or non-prescription drugs used were all associated with an statistically significant increase in the odds of reporting pain 12 years postpartum. Widespread pain was common and median expectation of improvement score was 5 on an 11-point numeric scale (interquartile range 2–7.50). More than one of five women (21.8%) reporting pain stated that they had been on sick leave the past 12 months and nearly 11% had been granted disability pension due to PPGP. No statistically significant differences were found between respondents and non-respondents regarding most background variables.ConclusionsThis study is unique as it is one of few long-term follow-up studies following women with PPGP of more than 11 years. The results show that spontaneous recovery with no recurrences is an unlikely scenario for a subgroup of women with PPGP. Persistency and/or duration of pain symptoms as well as widespread pain appear to be the strongest predictors of poor long-term outcome. Moreover, widespread pain is commonly associated with PPGP and may thus contribute to long-term sick leave and disability pension. A screening tool needs to be developed for the identification of women at risk of developing PPGP to enable early intervention.

Perianal fistulizing Crohn's disease: pathogenesis, diagnosis and therapy.

Perianal fistulizing Crohn's disease has a major negative effect on patient quality of life and is a predictor of poor long-term outcomes. Factors involved in the pathogenesis of perianal fistulizing Crohn's disease include an increased production of transforming growth factor β, TNF and IL-13 in the inflammatory infiltrate that induce epithelial-to-mesenchymal transition and upregulation of matrix metalloproteinases, leading to tissue remodelling and fistula formation. Care of patients with perianal Crohn's disease requires a multidisciplinary approach. A complete assessment of fistula characteristics is the basis for optimal management and must include the clinical evaluation of fistula openings, endoscopic assessment of the presence of proctitis, and MRI to determine the anatomy of fistula tracts and presence of abscesses. Local injection of mesenchymal stem cells can induce remission in patients not responding to medical therapies, or to avoid the exposure to systemic immunosuppression in patients naive to biologics in the absence of active luminal disease. Surgery is still required in a high proportion of patients and should not be delayed when criteria for drug failure is met. In this Review, we provide an up-to-date overview on the pathogenesis and diagnosis of fistulizing Crohn's disease, as well as therapeutic strategies.

神経性食思不振症の予後調査 : 遷延化予測因子としての家族背景と性格特徴(摂食障害の中・長期経過第30回日本心身医学会総会)

神経性食思不振症の予後調査 : 遷延化予測因子としての家族背景と性格特徴(摂食障害の中・長期経過第30回日本心身医学会総会)