Combination Of Clinical Features Research Articles

Diagnostic accuracy of whole spine magnetic resonance imaging in spinal tuberculosis validated through tissue studies.

Conventional diagnosis of spinal tuberculosis (TB) is based on a combination of clinical features, laboratory tests and imaging studies, since none of these individual diagnostic features are confirmatory. Despite the high sensitivity of MRI findings in evaluating spinal infections, its efficacy in diagnosing spinal TB is less emphasized and remains unvalidated through tissue studies. We reviewed consecutive patients evaluated for spondylodiscitis with documented clinical findings, MRI spine, and tissue analysis for histopathology, TB culture and genetic TB PCR. MRI features documented include location, contiguous/non-contiguous skip lesions, para/intraosseous abscess, subligamentous spread, vertebral collapse, abscess size/wall, disc involvement, end plate erosion and epidural abscess. Based on the results, patients were divided into two groups-CONFIRMED TB with positive culture/histopathology and NON-TB. The efficacy of MRI findings in accurately diagnosing spinal TB was compared between the two groups. Among 150 patients, 79 patients were TB positive, and 71 were TB negative. Three MRI parameters showed significant differences (p < 0.001), namely subligamentous spread (67/79, 84.8%), vertebral collapse > 50% (55/79, 69.6%) and large abscess collection with thin abscess wall (72/79, 91.1%) being strongly predictive of TB. Combination of MRI findings had a higher predictive value. 97.5% of TB positive patients had at least one of these three MRI features, 89.8% patients had any two and 58.2% had all three. Our study validated different MRI findings with tissue studies and showed spinal infections with large abscess with thin wall, subligamentous spread of abscess and vertebral collapse were highly suggestive of spinal tuberculosis. These slides can be retrieved under Electronic Supplementary Material.

The DM-scope registry: a rare disease innovative framework bridging the gap between research and medical care

BackgroundThe relevance of registries as a key component for developing clinical research for rare diseases (RD) and improving patient care has been acknowledged by most stakeholders. As recent studies pointed to several limitations of RD registries our challenge was (1) to improve standardization and data comparability; (2) to facilitate interoperability between existing RD registries; (3) to limit the amount of incomplete data; (4) to improve data quality. This report describes the innovative concept of the DM-Scope Registry that was developed to achieve these objectives for Myotonic Dystrophy (DM), a prototypical example of highly heterogeneous RD. By the setting up of an integrated platform attractive for practitioners use, we aimed to promote DM epidemiology, clinical research and patients care management simultaneously.ResultsThe DM-Scope Registry is a result of the collaboration within the French excellence network established by the National plan for RDs. Inclusion criteria is all genetically confirmed DM individuals, independently of disease age of onset. The dataset includes social-demographic data, clinical features, genotype, and biomaterial data, and is adjustable for clinical trial data collection. To date, the registry has a nationwide coverage, composed of 55 neuromuscular centres, encompassing the whole disease clinical and genetic spectrum. This widely used platform gathers almost 3000 DM patients (DM1 n = 2828, DM2 n = 142), both children (n = 322) and adults (n = 2648), which accounts for > 20% of overall registered DM patients internationally. The registry supported 10 research studies of various type i.e. observational, basic science studies and patient recruitment for clinical trials.ConclusionThe DM-Scope registry represents the largest collection of standardized data for the DM population. Our concept improved collaboration among health care professionals by providing annual follow-up of quality longitudinal data collection. The combination of clinical features and biomolecular materials provides a comprehensive view of the disease in a given population. DM-Scope registry proves to be a powerful device for promoting both research and medical care that is suitable to other countries. In the context of emerging therapies, such integrated platform contributes to the standardisation of international DM research and for the design of multicentre clinical trials. Finally, this valuable model is applicable to other RDs.

Systematic review of clinical prediction models to support the diagnosis of asthma in primary care

Diagnosing asthma is challenging. Misdiagnosis can lead to untreated symptoms, incorrect treatment and avoidable deaths. The best combination of clinical features and tests to achieve a diagnosis of asthma is unclear. As asthma is usually diagnosed in non-specialist settings, a clinical prediction model to aid the assessment of the probability of asthma in primary care may improve diagnostic accuracy. We aimed to identify and describe existing prediction models to support the diagnosis of asthma in children and adults in primary care. We searched Medline, Embase, CINAHL, TRIP and US National Guidelines Clearinghouse databases from 1 January 1990 to 23 November 17. We included prediction models designed for use in primary care or equivalent settings to aid the diagnostic decision-making of clinicians assessing patients with symptoms suggesting asthma. Two reviewers independently screened titles, abstracts and full texts for eligibility, extracted data and assessed risk of bias. From 13,798 records, 53 full-text articles were reviewed. We included seven modelling studies; all were at high risk of bias. Model performance varied, and the area under the receiving operating characteristic curve ranged from 0.61 to 0.82. Patient-reported wheeze, symptom variability and history of allergy or allergic rhinitis were associated with asthma. In conclusion, clinical prediction models may support the diagnosis of asthma in primary care, but existing models are at high risk of bias and thus unreliable for informing practice. Future studies should adhere to recognised standards, conduct model validation and include a broader range of clinical data to derive a prediction model of value for clinicians.

Chronic diarrhoea in adults: what not to miss.

Chronic diarrhoea remains a diagnostic challenge, with numerous causes and few effective symptomatic treatments. This review focuses on new methods for diagnosis of common disorders and alerts readers to rarer causes through a systematic approach to the underlying mechanisms. New strategies are emerging to stratify the need for endoscopic investigation. Faecal immunochemical testing, combined with standard blood tests, shows promise in excluding colorectal cancers, adenoma and inflammatory bowel disease, challenging the current use of faecal calprotectin. Serum analysis for markers of bile acid synthesis has been refined, potentially streamlining diagnostic pathways of bile acid malabsorption for those who are unable to access nuclear medicine scans, but the positive predictive value of faecal elastase in low prevalence populations has been questioned. Novel markers such as volatile organic compounds and stool DNA analyses continue to develop. A systematic approach to investigation of chronic diarrhoea will ensure all relevant causes are considered and minimize the chance of a missed diagnosis. Combination of clinical features with noninvasive testing supports a judicious approach to endoscopic investigations but further innovation will be needed to resolve the diagnostic challenge that diarrhoea poses.

Dynamic liver test patterns do not predict bile duct stones.

Numerous models have been developed to predict choledocholithiasis. Recent work has shown that these algorithms perform suboptimally. Identification of clinical predictors with high positive and negative predictive value would minimize adverse events associated with unnecessary diagnostic endoscopic retrograde cholangiopancreatography (ERCP) while limiting the use of expensive tests including magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS) for indeterminate cases. Consecutive unique inpatients who received their first ERCP at Los Angeles County Medical Center between January 2010 and November 2016 for suspected bile duct stones were reviewed. The primary outcome was the proportion of patients with specific combinations of liver enzyme patterns, transabdominal ultrasound, and clinical features who had stones confirmed on ERCP. As a secondary outcome, we assessed the performance of the American Society for Gastrointestinal Endoscopy (ASGE) risk stratification algorithm in our population. Of the 604 included patients, bile duct stones were confirmed in 410 (67.9%). Detailed assessment of liver enzyme patterns alone and in combination with clinical features and imaging findings yielded no highly predictive algorithms. Additionally, the ASGE high-risk criterion had a positive predictive value of only 68% for stones. For the 236 patients for whom MRCP was performed, this imaging modality was shown to have highest predictive value for the presence of stones on ERCP. Exhaustive exploration of various threshold values and dynamic patterns of liver enzymes combined with clinical features and basic imaging findings did not reveal an algorithm to accurately predict the presence of stones on ERCP. The ASGE risk stratification criteria were also insensitive in our population. Though desirable, there may be no "perfect" combination of clinical features that correlate with persistent bile duct stones. MRCP or EUS may be considered to avoid unnecessary ERCP and associated complications.

Deep stacked sparse auto-encoders for prediction of post-operative survival expectancy in thoracic lung cancer surgery.

Lung cancer is the leading cause of cancer death in men and women. The prognostic value of survival after lung cancer surgery has an important role in decision-making for surgeons and patients. The combination of clinical features and CT scan information for diagnosis, treatment and survival of patients with lung cancer increases the accuracy of prediction using machine learning. Therefore, creating a computer intelligent method with low error and high accuracy to predict survival is an important challenge, and it is beneficial for decreasing mortality from lung cancer, and for planning treatment. In this work, we implemented a deep stacked sparse auto-encoder (DSSAE) approach on a thoracic surgery data set for 470 patients, and our results contributing to deep learning based on 16 features were more precise than other suggested techniques for predicting post-operative survival expectancy in thoracic lung cancer surgery. The proposed method achieved a sensitivity of 94%, specificity of 82.86% and g-mean of 88.25%.

Primary Mediastinal B-Cell Lymphoma: Evaluation of Clinicopathologic Diagnosis Compared to Gene Expression Based Diagnosis in a Clinical Trial with CD30+ B-Cell Lymphomas

Primary Mediastinal B-Cell Lymphoma: Evaluation of Clinicopathologic Diagnosis Compared to Gene Expression Based Diagnosis in a Clinical Trial with CD30+ B-Cell Lymphomas

LATE-ONSET CYSTIC FIBROSIS IN AN ELDERLY MALE

Introduction Cystic fibrosis (CF) is described as a disease that manifests primarily in childhood, with only 7 percent diagnosed during adulthood. We describe a man with history of infertility and recurrent bronchitis who was diagnosed with CF at age 69. Case Description A 69-year-old with history of recurrent bronchitis since mid-age (once a year, quickly resolved with short course oral antibiotics) presented with refractory cough with yellowish sputum and sinusitis symptoms after a viral upper respiratory infection 18 months prior. He underwent several rounds of antibiotics and steroid taper but his symptoms quickly relapse after completing each treatment course. CT chest showed cylindrical type bronchiectasis. CT sinuses showed extensive mucosal thickening. Culture from his maxillary sinus and sputum grew pan-sensitive pseudomonas aeruginosa. His bronchial washing grew Methicillin-sensitive Staphylococcus aureus and Mycobacterium abscesses. Physical exam was consistent with chronic sinopulmonary infection, no digit clubbing. His comprehensive immunological deficiency workup was unrevealing. However, his sweat test showed chloride level of 68 to 73 mmol/L. In addition, his genetic test for CFTR showed compound heterozygote for the p.F508del pathogenic variant and [5T; 12TG] allele. The patient was infertile, although no absent vas deferens. There was no family history of CF. Patient was subsequently diagnosed with CF based upon combination of clinical characteristics and laboratory studies. Discussion Patients with CF may present at adult age in a diversity of clinical disciplines. Our case is a reminder that CF should be considered in differential diagnosis of bronchiectasis, even in elderly population.

MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes

MHC class II deficiency leads to defective CD4+ T-cell function that results from impaired antigen presentation. A genetic disorder in 1 of 4 genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency. To describe the clinical, immunological, and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC class II deficiency between 2012 and2017. An initial diagnosis based on the combination of clinical features and low HLA-DR expression by flow cytometry was confirmed by genetic analyses. Symptoms included failure to thrive (n= 9), persistent diarrhea (n= 5), and pneumonia (n= 8). Septicemia due to coagulase-negative staphylococci (n= 1) and Candida krusei (n= 1) was diagnosed. Nine patients orally received the live attenuated polio vaccine, of whom 3 developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, 1 carried a CIITA gene mutation, and none carried RFXAP gene mutations. Six of the 7 detected mutations were previously unreported mutations: c.431T>C, c.247_250delTCAG, and c.600delG in the RFXANK gene; c.116+1G>A and c.715C>T in the RFX5 gene; and c.929delA in the CIITA gene. Given that Egypt is a North African country with a high rate of consanguinity, MHC class II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based on suspicious clinical signs and laboratory diagnosis because the defect can be missed by T-cell receptor excision circles based on neonatal screening.

Cerebrospinal Fluid Protein Level and Nerve Conduction Study as Short-Term Prognostic Marker of Guillain Barré Syndrome

Background: Guillain Barré Syndrome (GBS) diagnosis is based on a combination of clinical features, Nerve conduction studies (NCS) and analysis of the cerebrospinal fluid (CSF) which eventually assist in monitoring disease progression as well as the efficacy of immunotherapy. The main objective of this study was to determine the relation of CSF protein level and nerve conduction study with short-term prognosis of GBS patients. Methods: This observational study was carried out in the Department of Neurology and Medicine, Dhaka Medical College Hospital, Dhaka during the period August, 2017 to July, 2018. Total 50 patients suffering from GBS were enrolled in this study. Lumber puncture (LP) and NCS were done at day 10 of symptom onset. Results: In this study majority (87.5%) of the patients had GBS Disability score &lt;3 in demyelinating and 16(47.1%) in axonal on day 90. Three fourth (75.0%) patients EGRIS score was ³3 in demyelinating and 34(100.0%) in axonal and mEGOS it was revealed that more than two third (68.8%) patients mEGOS score was ³6 in Demyelinating and 33(97.1%) in axonal. More than three fourth (76.0%) patients ³6 mEGOS score in CSF protein &lt;100 (mg/dl) and 25(100.0%) in CSF protein ³100 (mg/dl). Multiple logistic regression analysis showing a subject with axonal GBS had 1.579 (95.0% C.I 1.717 to 3.475), CSF Protein had 1.013 (95.0% C.I. 1.001 to 1.026) (PÂ0.05%). Conclusion: CSF analysis for protein and NCS examination appeared as the essential short term predictors in evaluating diagnostic accuracy and prognostic determinant of GBS early. Bangladesh Journal of Neuroscience 2018; Vol. 34 (2): 79-84

Does the Implementation of a Pediatric Appendicitis Pathway Promoting Ultrasound Work Outside of a Children’s Hospital?: Kobayashi E, Johnson B, Goetz K, et al. Am J Surg. 2018; 215(5):917-920

The diagnosis of appendicitis in children relies on a combination of clinical features and diagnostic imaging, whether it be ultrasound (US) or Computed Tomography (CT) scan. In recent years there has been a greater emphasis on diagnosis by clinical scoring systems in concert with ultrasound in order to reduce radiation exposure. Many children’s hospitals have adopted clinical pathways to facilitate diagnosis and spare CT scans. This study sought to demonstrate the efficacy of an appendicitis diagnostic pathway in community settings.

The Role of Liver Transplantation in Alcoholic Hepatitis.

Acute alcoholic hepatitis is a syndrome of jaundice and hepatic decompensation that occurs with excessive alcohol consumption. The diagnosis can be made with a combination of clinical characteristics and laboratory studies, though biopsy may be required in unclear cases. Acute alcoholic hepatitis can range from mild to severe disease, as determined by a Maddrey discriminant function ≥32. Mild forms can be managed with supportive care and abstinence from alcohol. While mild form has an overall good prognosis, severe alcoholic hepatitis is associated with an extremely high short-term mortality of up to 50%. Additional complications of severe alcoholic hepatitis can include hepatic encephalopathy, gastrointestinal bleeding, renal failure, and infection; these patients frequently require intensive care unit admission. Corticosteroids may have short-term benefit in this group of patients if there are no contraindications; however, a subset of patients do not respond to steroids. New emerging therapies, which target hepatic regeneration, bile acid metabolism, and extracorporeal liver support, are being investigated. Liver transplantation for alcoholic liver disease was traditionally only considered in patients who have achieved 6 months of abstinence, in part due to social and ethical concerns regarding the use of a limited resource. However, the majority of patients with severe alcoholic hepatitis who fail medical therapy will not live long enough to meet this requirement. Recent studies have demonstrated that early liver transplantation in carefully selected patients with severe alcoholic hepatitis who fail medical therapy can provide a significant survival benefit and yields survival outcomes comparable to liver transplantation for other indications, with 6-month survival rates ranging from 77% to 100%. Alcohol relapse posttransplantation remains an important challenge, and heavy consumption can contribute to graft loss and mortality. Future investigation should address the substantial post-liver transplantation recidivism rate, from improving selection criteria to increasing posttransplantation substance abuse treatment resources.

Sarcoidosis Diagnostic Score: A Systematic Evaluation to Enhance the Diagnosis of Sarcoidosis

The diagnosis of sarcoidosis is made by the combination of clinical features and biopsy results. The clinical features of sarcoidosis can be quite variable. We developed a Sarcoidosis Diagnostic Score (SDS) to summarize the clinical features of patients with possible sarcoidosis. Biopsy-confirmed patients with sarcoidosis seen during a 7-month period at the University of Cincinnati sarcoidosis clinic were prospectively identified. Patients with nonsarcoidosis seen at the same clinic were used as control patients. Using a modified World Association of Sarcoidosis and Other Granulomatous Disorders organ assessment instrument, we scored all patients for presence of biopsy,≥1 highly probable symptom, and≥1 at least probable symptom for each area. Two sarcoidosis scores were generated: SDS biopsy (with biopsy) and SDS clinical (without biopsy). The 980 evaluable patients were divided into two cohorts: an initial 600 patients (450 with biopsy-confirmed sarcoidosis, 150 control patients) to establish cutoff values for SDS biopsy and an SDS clinical and a validation cohort of 380 patients (103 biopsy-confirmed patients with sarcoidosis and 277 control patients). The best cutoff value for SDS biopsy was≥ 6 (sensitivity, 99.3%; specificity, 100%). For the total the 980 patients, an SDS clinical≥ 3 had a sensitivity of 90.6%, specificity of 88.5%, and a likelihood ratio of 7.9. An SDS clinical score≥ 4 had a lower sensitivity of (76.9%) but higher specificity (98.6%). For sarcoidosis, the presence of specific clinical features, especially multiorgan involvement, can enhance the diagnostic certainty. The SDS scoring system quantitated the clinical features consistent with sarcoidosis.

Molecular and Clinical Characterization of Chikungunya Virus Infections in Southeast Mexico.

Chikungunya fever is an arthropod-borne infection caused by Chikungunya virus (CHIKV). Even though clinical features of Chikungunya fever in the Mexican population have been described before, there is no detailed information. The aim of this study was to perform a full description of the clinical features in confirmed Chikungunya-infected patients and describe the molecular epidemiology of CHIKV. We evaluated febrile patients who sought medical assistance in Tapachula, Chiapas, Mexico, from June through July 2015. Infection was confirmed with molecular and serological methods. Viruses were isolated and the E1 gene was sequenced. Phylogeny reconstruction was inferred using maximum-likelihood and maximum clade credibility approaches. We studied 52 patients with confirmed CHIKV infection. They were more likely to have wrist, metacarpophalangeal, and knee arthralgia. Two combinations of clinical features were obtained to differentiate between Chikungunya fever and acute undifferentiated febrile illness. We obtained 10 CHIKV E1 sequences that grouped with the Asian lineage. Seven strains diverged from the formerly reported. Patients infected with the divergent CHIKV strains showed a broader spectrum of clinical manifestations. We defined the complete clinical features of Chikungunya fever in patients from Southeastern Mexico. Our results demonstrate co-circulation of different CHIKV strains in the state of Chiapas.

Editors' note: Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium

“Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium” proposed new criteria for the diagnosis of dementia with Lewy bodies (DLB), helping to distinguish DLB from Parkinson disease with dementia. Dr. Abe agrees with the need for new criteria and discusses how the hypothesis of Braak et al. of the rostral progression of brainstem synucleinopathy is not observed in DLB. Drs. Uchihara and Toru comment that the new criteria, in which combinations of clinical features and biomarkers lead to the diagnosis of possible or probable DLB, will make diagnosis easier and more precise. In the new criteria, reduced dopamine transporter (DAT) uptake in the basal ganglia seen on SPECT or PET was considered an indicative biomarker and, therefore, combined with one core clinical feature, is sufficient to diagnose probable DLB. Drs. Parmera et al. argue that low DAT uptake may be better classified as a supportive biomarker given that it is not as helpful in differentiating between diseases of presynaptic dopaminergic deficiency. Drs. Wang et al. request that visual hallucinations be better defined and further research be undertaken into the 1-year rule between the onset of dementia and parkinsonism. Author McKeith responds to all correspondents. He describes a study currently underway looking at modifying the existing DLB staging system using more extensive neuropathologic evaluation, explains the consortium's decision on including DAT uptake as an indicative biomarker rather than a supportive one, and offers guidance on visual hallucinations and the 1-year rule. “Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium” proposed new criteria for the diagnosis of dementia with Lewy bodies (DLB), helping to distinguish DLB from Parkinson disease with dementia. Dr. Abe agrees with the need for new criteria and discusses how the hypothesis of Braak et al. of the rostral progression of brainstem synucleinopathy is not observed in DLB.

Three Novel NF1 Gene Mutations in a Cohort of Bulgarian Neurofibromatoses Patients

Neurofibromatosis (NF) is a clinically heterogeneous autosomal dominant disorder. Three distinct forms have been identified: neurofibromatosis type 1 (NF1), type 2 (NF2) and schwannomatosis. In the present study, we report clinical and genetic findings in the NF1 and NF2 genes in a cohort of 27 Bulgarian patients, with 18 cases (67%) genetically verified. Both NF1 and NF2 genes were screened by Sanger sequencing on DNA samples. The Sanger negative samples were screened by Multiplex Ligation-dependent Probe Amplification (MLPA) for deletions and duplications. The results from genetic testing revealed three novel mutations and fifteen previously reported ones (13 in the NF1 gene and 2 in the NF2 gene). The novel variants in the NF1 gene are a splice site mutation c.4725-1G>A, a small deletion of five bases c.823delATCTT, p.Leu275ValfsTer14, and a single base duplication c.6547dupC, p.Arg2183ProfsTer11. The novel splice site mutation is manifested by multiple “cafe au lait” macules and neurofibromas. Both novel out of frame mutations were found in patients with multiple “cafe au lait” spots and focal epilepsy. A segmental neurofibromatosis (SNF1) is restricted to one or more body segments. Here we present a case with SNF1 caused by a somatic deletion of exons 1 to 12 of the NF1 gene which is manifested by multiple neurofibromas in the right hand. Two nonsense mutations are found in the NF2 gene. Our study adds three novel mutations to the NF1 mutation spectra and contributes to the clinical-genetic NF1-characterization. Here we report strikingly different phenotypic spectra caused by the same mutation in a single family. Our findings contribute to the genotype- phenotype correlations which are difficult to establish, due to the extremely complex NF phenotype being a combination of clinical features.

EXPRESSION OF THE GROWTH HORMONE SECRETAGOGUE RECEPTOR AND GHRELIN IN HUMAN HEART FAILURE

Heart failure (HF) is defined as occurring when the heart is unable to provide adequate blood flow and oxygen to organs across the body. Currently, a diagnosis of HF is made using a combination of clinical features, cardiac imaging, and detection of certain biomarkers in the circulation, notably BNP. However, a biomarker specific to cardiac tissue and that reflects the heart’s contractile state is lacking. Our group is characterizing the growth hormone secretagogue receptor (GHSR) and its ligand ghrelin as possible cardiac-specific biomarkers for HF. We have previously developed a fluorescent analog of ghrelin, Ghrelin(1-18, Lys18(Cy5), to detect GHSR in cardiac tissue in situ. We hypothesize that GHSR and ghrelin are biomarkers for the early detection of HF. We obtained samples of cardiac tissue from 10 cardiac transplant patients at the time of organ harvesting and serial post-transplant biopsies. Samples from the LV and RA of the explanted hearts, and biopsies from the newly-transplanted hearts (weekly for 4 weeks, monthly for 6 months, and 1 year post-Tx). GHSR levels were measured using Ghrelin(1-18, Lys18(Cy5) and ghrelin and BNP were measured using fluorescent antibodies. All samples were quantified using fluorescence microscopy. Fibrotic tissue was detected using Masson’s trichrome stain. Levels of all markers were compared between the explanted heart and the healthy biopsies using two-tailed t-test, one-way ANOVA and Tukey’s test and Pearson’s correlation (p < 0.05). GHSR and fibrosis levels increased and were highly variable in explanted hearts when compared to the healthy biopsies which had a much lower level of variability. Within 3 individual patients, there were significant differences (p < 0.001, p < 0.05, p < 0.01 respectively) between the explanted heart (LV and RA) and the short-term biopsies of the healthy heart (weeks 1-4) of both GHSR and ghrelin but not BNP. Within the entire transplant patient cohort (n=10), there was a strong positive correlation between both ghrelin and BNP (r2=0.575, p < 0.0001) and ghrelin and GHSR (r2=0.7033, p < 0.0001). GHSR and ghrelin showed elevated expression and significant differences in 3 of the 10 patients with end stage HF where BNP showed no significant differences indicating the increased sensitivity of GHSR and ghrelin in HF detection. Correlation between ghrelin and BNP, and ghrelin and GHSR in cardiac tissue may show evidence of a ghrelin/GHSR system working independently in the myocardium. These results indicate the potential use of ghrelin and GHSR as new cardiac-specific biomarkers that can help with the detection of HF.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Predictors of neurologic deficit on discharge and in-hospital mortality of pediatric tuberculous meningitis patients with hydrocephalus who undergo ventriculoperitoneal shunting

Objective: To determine predictors of neurologic deficit on discharge and in-hospital mortality among TBM patients with hydrocephalus who undergo VPS insertion. Methods: This was a retrospective cross-sectional study from January 2005–December 2015. The diagnosis of TBM were based on a combination of clinical features, CSF findings, and neuroimaging appearances. Results: Eighty-three children with TBM who underwent VPS. Their median age was 3 years old, and 61.45% were males. Nearly half of the patients were underweight. A previous and family histories of PTB was reported in 15.66% and 19.28%, respectively. The majority of patients admitted were Stage II (78.31%). More than half had increased CSF protein, and reduced sugar and WBC on analysis. Basilar enhancement in 15.58% and infarction in 3.95% of the patients were noted by neuroimaging. CUS showed rim/halo, increased periventricular echogenicity, and flattened sulci. Duration from onset of symptoms to detection of hydrocephalus was less than two weeks in 26% of Stage II and 41% of Stage III. The duration of altered sensorium prior surgery was less than 24 h for most of the patients across stages. More than half of patients in Stage III with severe hydrocephalus and GCS below 8. The mRS distribution among the Stage II patients; 6.15% normal, 72.31% with neurologic deficit, 10.77% severely debilitated, and 10.77% expired while in Stage III; 47.06% with deficits, 11.76% severely debilitated, and 41.18% expired. Patients whose CSF protein and severe hydrocephalus were poor mRS scores on discharge (95% CI 1.1044 to 7.6062, p = 0.031). Conclusion: TBM affects mainly children less than 5 years of age and is still a serious public health problem. CSF protein and the severity of hydrocephalus are strongly associated with high mortality rate.

Predictive Value of Clinical Findings and Plasma Biomarkers after Fourteen Days of Prednisone Treatment for Acute Graft-versus-host Disease

We examined the hypothesis that plasma biomarkers and concomitant clinical findings after initial glucocorticoid therapy can accurately predict failure of graft-versus-host-disease (GVHD) treatment and mortality. We analyzed plasma samples and clinical data in 165 patients after 14 days of glucocorticoid therapy and used logistic regression and areas under receiver-operating characteristic curves (AUC) to evaluate associations with treatment failure and nonrelapse mortality (NRM). Initial treatment of GVHD was unsuccessful in 49 patients (30%). For predicting GVHD treatment failure, the best clinical combination (total serum bilirubin and skin GVHD stage: AUC, .70) was competitive with the best biomarker combination (T cell immunoglobulin and mucin domain 3 [TIM3] and [interleukin 1 receptor family encoded by the IL1RL1 gene, ST2]: AUC, .73). The combination of clinical features and biomarker results offered only a slight improvement (AUC, .75). For predicting NRM at 1 year, the best clinical predictor (total serum bilirubin: AUC, .81) was competitive with the best biomarker combination (TIM3 and soluble tumor necrosis factor receptor-1 [sTNFR1]: AUC, .85). The combination offered no improvement (AUC, .85). Infection was the proximate cause of death in virtually all patients. We conclude that after 14 days of glucocorticoid therapy, clinical findings (serum bilirubin, skin GVHD) and plasma biomarkers (TIM3, ST2, sTNFR1) can predict failure of GVHD treatment and NRM. These biomarkers reflect counter-regulatory mechanisms and provide insight into the pathophysiology of GVHD reactions after glucocorticoid treatment. The best predictive models, however, exhibit inadequate positive predictive values for identifying high-risk GVHD cohorts for investigational trials, as only a minority of patients with high-risk GVHD would be identified and most patients would be falsely predicted to have adverse outcomes.

The role of ECMO in acute interstitial lung disease

Interstitial lung disease comprises a heterogeneous group of histologically distinct pathological entities characterized by a diffuse inflammatory process affecting the lung parenchyma. Classification of interstitial lung disease is complex and usually determined by a combination of clinical features, radiological, particularly computed tomography, appearance, and findings at lung biopsy. Interstitial lung disease presentations can range from slowly progressive interstitial pneumonitis to more rapidly progressive vasculitic, eosinophilic, and acute fibrotic diseases. In the acute form, interstitial lung disease can, over a period of days, manifest as bilateral diffuse pulmonary infiltrates, causing a significant disturbance of respiratory function. Patients characteristically have very poor dynamic compliance and poor gas exchange. The outcome of patients with interstitial lung disease admitted to the Intensive Care Unit (ICU) has historically been very poor. This is thought to be a combination of both the lack of reversibility of the underlying respiratory problem and further damage to the lungs associated with necessarily invasive mechanical ventilation.1–3 The pro-inflammatory effects of invasive ventilation have been well described and are proportional to both tidal ventilation and pressure within the lung. There are a number of potential treatment options now available, which may help to modify the course of the disease,4 particularly in cases where there is a very high level of inflammation within the lung. Treatment options currently available include high-dose steroids, rituximab, and cyclophosphamide. Recently patients with acute interstitial lung disease have been offered extracorporeal membrane oxygenation (ECMO) as both a life-sustaining supportive therapy and a means of avoiding ventilator-induced lung injury, and results are improving, particularly in patients with acute interstitial lung disease.5 One of the benefits of ECMO is that it can allow patients to be awake and undertake physical and pulmonary rehabilitation.6 This may be of particular benefit in the interstitial lung disease population, where a bridge to transplant is being considered. The latest evidence for the use of ECMO in interstitial lung disease will be reviewed, including clinical phenotypes which appear to particularly benefit from ECMO as a bridge to recovery. Some patients who present with what is assumed to be an infective pneumonia will ultimately progress to developing a progressive acute interstitial lung disease and it is essential to differentiate such patients from those with acute respiratory distress syndrome. In patients with acute interstitial lung disease, there are treatments which may modify the course of the disease, whereas the predominant management of acute respiratory distress syndrome is largely avoiding lung inflammation to prevent the progression. A strategy for investigation and the key clinical and physiological indicators of potential acute interstitial lung disease will be discussed.