Predisposition,Insult/Infection,Response and Organ Dysfunction (PIRO): A Pilot Clinical Staging System for Hospital Mortality in Patients with Infection

Purpose

To develop a clinical staging system based on the PIRO concept (Predisposition, Infection, Response and Organ dysfunction) for hospitalized patients with infection.

Methods

One year prospective cohort study of all hospitalized patients with infection (n = 1035), admitted into a large tertiary care, university hospital. Variables associated with hospital mortality were selected using logistic regressions. Based on the regression coefficients, a score for each PIRO component was developed and a classification tree was used to stratify patients into four stages of increased risk of hospital mortality. The final clinical staging system was then validated using an independent cohort (n = 186).

Results

Factors significantly associated with hospital mortality were • for Predisposition: age, sex, previous antibiotic therapy, chronic hepatic disease, chronic hematologic disease, cancer, atherosclerosis and a Karnofsky index<70; • for Insult/Infection: type of infection • for Response: abnormal temperature, tachypnea, hyperglycemia and severity of infection and • for Organ dysfunction: hypotension and SOFA score≥1. The area under the ROC curve (CI_95%) for the combined PIRO model as a predictor for mortality was 0.85 (0.82–0.88). Based on the scores for each of the PIRO components and on the cut-offs estimated from the classification tree, patients were stratified into four stages of increased mortality rates: stage I: ≤5%, stage II: 6–20%, stage III: 21–50% and stage IV: >50%. Finally, this new clinical staging system was studied in a validation cohort, which provided similar results (0%, 9%, 31% and 67%, in each stage, respectively).

Conclusions

Based on the PIRO concept, a new clinical staging system was developed for hospitalized patients with infection, allowing stratification into four stages of increased mortality, using the different scores obtained in Predisposition, Response, Infection and Organ dysfunction. The proposed system will likely help to define inclusion criteria in clinical trials as well as tailoring individual management plans for patients with infection.     

根据“肠-肾轴”理论治疗慢性肾脏病的研究进展

有研究报道在慢性肾脏病的发生发展过程中可发现一系列肠道变化,并有学者用"肠-肾轴"理论阐述肾脏病中肠道的变化以及疾病过程中肾脏与肠道之间的联系,提示调节肠道菌群或可成为治疗慢性肾脏病的新方法。本文根据"肠-肾轴"理论,综述了在慢性肾脏病发展过程中肠道出现的变化,如肠内代谢物异常、肠道损伤以及肠道菌群失调等。以慢性肾脏病发生发展过程中肠道的异常变化为治疗切入点,总结了以大黄为主的中药在调节肠道功能、修复肠道屏障、纠正肠道代谢物异常等方面具有的显著疗效,为治疗慢性肾脏病及减少并发症等提供新的治疗思路和新方法。     

Fractal and spectral dimension analysis of liver fibrosis in needle biopsy specimens

OBJECTIVE: To evaluate the usefulness of a reliable and reproducible mathematical scoring system based on fractal geometry for quantifying the irregular pattern in fibrosis commonly seen in liver biopsy specimens from chronic liver diseases. STUDY DESIGN: The study used 26 standard liver biopsy specimens obtained from patients with chronic hepatitis C virus-related liver disease. The degree of fibrosis in each specimen was estimated using a quantitative scoring system based on the computer-assisted evaluation of both the fractal and spectral dimensions of deposited collagen. The fractal dimension was then compared with the percent area of collagen measured using an image analysis system. RESULTS: The fractional dimension of its irregular shape defines fibrosis as a natural fractal structure. The complex distribution of its collagenous components (unmeasurable by means of the usual morphometric parameters) can be optimally quantified using a single numerical score that seems to be a better alternative to the semiquantitative methods adopted so far. The proposed method is reproducible, rapid and inexpensive; furthermore, supported by specific software, its mathematical approach excludes subjectivity and eliminates the external factors capable of influencing staging and classification. CONCLUSION: This study demonstrated that it is possible to quantify the irregularity of the structures of the liver in an objective manner and that the box-counting fractal dimension does not depend on the amount of collagen deposited on the slide. Furthermore, as has been found in other fields of investigation, study of the fractal properties of the liver is likely to reveal more about its structure and the pathogenesis of liver diseases.     

Fatty Kidney Disease: A New Renal And Endocrine Clinical Entity? Describing the Role of the Kidney in Obesity,Metabolic Syndrome,and Type 2 Diabetes

Objective: To determine whether fatty kidney disease deserves be designated as a distinct clinical entity similar to fatty liver disease.Methods: Analysis and interpretation of the literature in a novel conceptual framework.Results: The kidney contributes to hyperglycemia, hypertension, inflammatory cytokines, and thus to diabetes and metabolic syndrome. Fat accumulation in and around the kidney drives this process and contributes to progression of chronic kidney disease itself. Weight loss improves these complications of fatty kidney. Diagnosis currently must be inferred from comorbidities but ultimately should be made by imaging once the importance of fatty kidney disease is established, much like fatty liver disease.Conclusion: Fatty kidney disease merits designation as a specific clinical entity similar to fatty liver disease. Greater attention to this may help encourage research into ameliorating the negative consequences of fatty kidney disease and developing new therapies.Abbreviations: BP = blood pressure; CKD = chronic kidney disease; CT = computed tomography; ESRD = end-stage renal disease; FFA = free fatty acid; FKD = fatty kidney disease; GFR = glomerular filtration rate; MetS = metabolic syndrome; MRI = magnetic resonance imaging; NAFLD = nonalcoholic fatty liver disease; RAAS = renin-angiotensin system; SGLT2 = sodium-glucose cotransporter 2; SNS = sympathetic nervous system; T2D = type 2 diabetes; TG = triglyceride     

American Association of Clinical Endocrinology Consensus Statement: Addressing Stigma and Bias in the Diagnosis and Management of Patients with Obesity/Adiposity-Based Chronic Disease and Assessing Bias and Stigmatization as Determinants of Disease Severity

ObjectiveTo focus on the intersection of perception, diagnosis, stigma, and weight bias in the management of obesity and obtain consensus on actionable steps to improve care provided for persons with obesity.MethodsThe American Association of Clinical Endocrinology (AACE) convened a consensus conference of interdisciplinary health care professionals to discuss the interplay between the diagnosis of obesity using adiposity-based chronic disease (ABCD) nomenclature and staging, weight stigma, and internalized weight bias (IWB) with development of actionable guidance to aid clinicians in mitigating IWB and stigma in that context.ResultsThe following affirmed and emergent concepts were proposed: (1) obesity is ABCD, and these terms can be used in differing ways to communicate; (2) classification categories of obesity should have improved nomenclature across the spectrum of body mass index (BMI) using ethnic-specific BMI ranges and waist circumference (WC); (3) staging the clinical severity of obesity based on the presence and severity of ABCD complications may reduce weight-centric contribution to weight stigma and IWB; (4) weight stigma and internalized bias are both drivers and complications of ABCD and can impair quality of life, predispose to psychological disorders, and compromise the effectiveness of therapeutic interventions; (5) the presence and of stigmatization and IWB should be assessed in all patients and be incorporated into the staging of ABCD severity; and (6) optimal care will necessitate increased awareness and the development of educational and interventional tools for health care professionals that address IWB and stigma.ConclusionsThe consensus panel has proposed an approach for integrating bias and stigmatization, psychological health, and social determinants of health in a staging system for ABCD severity as an aid to patient management. To effectively address stigma and IWB within a chronic care model for patients with obesity, there is a need for health care systems that are prepared to provide evidence-based, person-centered treatments; patients who understand that obesity is a chronic disease and are empowered to seek care and participate in behavioral therapy; and societies that promote policies and infrastructure for bias-free compassionate care, access to evidence-based interventions, and disease prevention.     

Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study

Pulmonary hypertension (PH) is common in patients with dialysis-dependent chronic kidney disease and is an independent predictor of mortality. However, specific hemodynamics of the pulmonary circulation, changes induced by hemodialysis and characterization into pre- or postcapillary PH have not been evaluated in patients with chronic kidney disease. We assessed consecutive patients with end-stage chronic kidney disease in WHO FC ≥ II with dyspnea unexplained by other causes on hemodialysis (group 1, n = 31) or without dialysis (group 2, n = 31) using right heart catheterization (RHC). In group 1, RHC was performed before and after dialysis. In end-stage chronic kidney disease, prevalence of precapillary PH was 13% (4/31), and postcapillary PH was discovered in 65% (20/31). All four cases of precapillary PH were unmasked after dialysis. In group 2, two cases of precapillary PH were detected (6%), and postcapillary PH was diagnosed in 22 cases (71%). This is the first study examining a large cohort of patients with chronic kidney disease invasively by RHC for the prevalence of PH. The prevalence of precapillary PH was 13% in patients with end-stage kidney disease. That suggests careful screening for precapillary PH in this selected patient population. RHC should be performed after hemodialysis.     

Temporal progress model of metabolic syndrome for clinical decision support system

The development of an integrated and personalized healthcare system is becoming an important issue in the modern healthcare industry. One of main objectives of integrated healthcare system is to effectively manage patients having chronic diseases that require long term care and its temporal information plays an important role to manage the statuses of diseases. Thus, a patient having chronic disease needs to visit the hospital periodically, which generates large volume of medical examination data. Among the various chronic diseases, metabolic syndrome (MS) has become a popular chronic disease in many countries. There have been efforts to develop an MS risk quantification and prediction model and to integrate it into personalized healthcare system, so as to predict the risk of having MS in the future. However, the development of methods for temporal progress management of metabolic syndrome has not been widely investigated. This paper proposes a method for identifying the temporal progress of MS patients' status based on the chronological clustering methodology. To investigate the temporal changes of disease status, we develop a chronological distance variance model that quantifies the difference of areal similarity degree (ASD) values between estimated and examined results of MS risk factors. We evaluate the clinical effectiveness of the temporal progress model by using sample subjects' examination results that have been measured for 10 years. We further elaborate the accuracy of the proposed temporal progress estimation method by using multiple linear regression method. Then, we develop a tier-based patients' MS status classification based on the chronological distance variance. The tier classification is based on the sensitivity for temporal change of MS status according to different values of control range of chronological distance variance. Our proposed temporal change identification method and patients' tier classification are expected to be incorporated with the integrated healthcare systems to help physicians with identifying the temporal progress of MS patients' health status and MS patients with self-management at home environments.     

Soluble thrombomodulin reduces inflammation and prevents microalbuminuria induced by chronic endothelial activation in transgenic mice

Chronic kidney disease pathogenesis involves both tubular and vascular injuries. Despite abundant investigations to identify the risk factors, the involvement of chronic endothelial dysfunction in developing nephropathies is insufficiently explored. Previously, soluble thrombomodulin (sTM), a cofactor in the activation of protein C, has been shown to protect endothelial function in models of acute kidney injury. In this study, the role for sTM in treating chronic kidney disease was explored by employing a mouse model of chronic vascular activation using endothelial-specific TNF-α-expressing (tie2-TNF) mice. Analysis of kidneys from these mice after 3 mo showed no apparent phenotype, whereas 6-mo-old mice demonstrated infiltration of CD45-positive leukocytes accompanied by upregulated gene expression of inflammatory chemokines, markers of kidney injury, and albuminuria. Intervention with murine sTM with biweekly subcutaneous injections during this window of disease development between months 3 and 6 prevented the development of kidney pathology. To better understand the mechanisms of these findings, we determined whether sTM could also prevent chronic endothelial cell activation in vitro. Indeed, treatment with sTM normalized increased chemokines, adhesion molecule expression, and reduced transmigration of monocytes in continuously activated TNF-expressing endothelial cells. Our results suggest that vascular inflammation associated with vulnerable endothelium can contribute to loss in renal function as suggested by the tie2-TNF mice, a unique model for studying the role of vascular activation and inflammation in chronic kidney disease. Furthermore, the ability to restore the endothelial balance by exogenous administration of sTM via downregulation of specific adhesion molecules and chemokines suggests a potential for therapeutic intervention in kidney disease associated with chronic inflammation.     

Reconociendo el virus del chikunguña

The chikungunya virus (CHIKV) is an Alphavirus that belongs to the Old World group. These arthritogenic viruses cause a febrile illness characterized by arthralgias and myalgias.Although fatal cases during CHIKV infection are rare, the disease may be disabling and generate a broad spectrum of atypical manifestations, such as cardiovascular, respiratory, eye, kidney, and skin complications, among others. When joint pain persists for three or more months, it results in the chronic form of the disease called post-chikungunya chronic inflammatory rheumatism, which constitutes the main disease sequel. CHIKV is not considered a neurotropic virus; however, it can affect the central nervous system, especially in children and the elderly, causing severe and permanent sequelae.CHIKV outbreaks had been previously reported in Africa, Asia, and Europe, but the virus introduction to the American continent was documented until the end of 2013. Since then, the virus has spread to 45 countries and territories causing near two million cases in just two years. This review describes the molecular biology, clinical manifestations, pathogenesis, and significant post-infection complications of CHIKV. Additionally, it collects published information about the outbreak in Colombia and the American continent between 2014 and 2020.     

Hereditäre Nierentumoren

About 1–4% of all kidney tumors are assigned to specific germ-line alterations. Kidney tumors are very heterozygous. A new classification system has been established based on pathomorphological and genetic criteria. Each of the four most common tumor types is related to a hereditary form with some specific genes being involved. Today, at least ten different hereditary conditions are known to be associated with kidney tumors. This review focuses on currently available measures for the individual management of these rare syndromic and nonsyndromic hereditary conditions.     

Assessment of the potential iridology for diagnosing kidney disease using wavelet analysis and neural networks

Alternative or complementary medicine emphasizes therapies that are claimed to improve quality of life, prevent disease, and address conditions that conventional medicine has limited success in curing. There are many techniques which are prevalent in many countries and these can cause harm if not scientifically evaluated. The objective of this paper is to validate the use of iridology to diagnose kidney abnormalities. Two subject groups were evaluated: one was 168 subjects free from kidney disease and the other was 172 subjects with chronic renal failure. The procedure to acquire, process and classify the iris images was designed in such a way that avoids any dependency on the iridologists by using wavelet analysis and Adaptive Neuro-Fuzzy Inference System. The results show a correct classification for both subjects with kidney problems and normal subjects of 82% and 93%, respectively. The proposed technique conducted on a systemic disease with ocular manifestations showed encouraging results. However, it is necessary to perform extensive studies with diseases that do not have ocular manifestations according to conventional medicine in order to validate iridology as a valid scientific technique.     

An automatic EEG-based sleep staging system with introducing NAoSP and NAoGP as new metrics for sleep staging systems

Different biological signals are recorded in sleep labs during sleep for the diagnosis and treatment of human sleep problems. Classification of sleep stages with electroencephalography (EEG) is preferred to other biological signals due to its advantages such as providing clinical information, cost-effectiveness, comfort, and ease of use. The evaluation of EEG signals taken during sleep by clinicians is a tiring, time-consuming, and error-prone method. Therefore, it is clinically mandatory to determine sleep stages by using software-supported systems. Like all classification problems, the accuracy rate is used to compare the performance of studies in this domain, but this metric can be accurate when the number of observations is equal in classes. However, since there is not an equal number of observations in sleep stages, this metric is insufficient in the evaluation of such systems. For this purpose, in recent years, Cohen’s kappa coefficient and even the sensitivity of NREM1 have been used for comparing the performance of these systems. Still, none of them examine the system from all dimensions. Therefore, in this study, two new metrics based on the polygon area metric, called the normalized area of sensitivity polygon and normalized area of the general polygon, are proposed for the performance evaluation of sleep staging systems. In addition, a new sleep staging system is introduced using the applications offered by the MATLAB program. The existing systems discussed in the literature were examined with the proposed metrics, and the best systems were compared with the proposed sleep staging system. According to the results, the proposed system excels in comparison with the most advanced machine learning methods. The single-channel method introduced based on the proposed metrics can be used for robust and reliable sleep stage classification from all dimensions required for real-time applications.Electronic supplementary materialThe online version of this article (10.1007/s11571-020-09641-2) contains supplementary material, which is available to authorized users.     

La lymphoscintigraphie dans la prise en charge thérapeutique des œdèmes des membres par les soins de santé en Belgique

Limbedemas of lymphatic origin, either primary, or secondary, represent a chronic disease sometimes heavy to bear by patients who suffer from them. These lymphedemas imply specific care by physical therapists trained to the use of different therapeutic approaches. Until a few years, only the treatments of secondary lymphedemas after radiotherapy and/or complete nodal dissection for cancer were reimbursed by the national health insurance system in Belgium. The introduction of the primary congenital lymphedemas as a disease also reimbursed raised several problems and led to a redefinition of these situations and of their cares. The definition and classification of the lymphedemas in view of the reimbursement of their treatments by the national health insurance system are now officially based (not only on the sole clinical history but) mainly on their clinical severity and/or also on the result of their lymphoscintigraphic investigation (according to a methodological protocol and to diagnostic criteria adopted at the national level). The reimbursements of the treatments by the physical therapists were also adapted and improved. The lymphocintigraphic investigations of the limbedemas became so essential in the management of the lymphedematous situations and in the reimbursement of their physical treatments in Belgium.     

Fractal dimension rectified meter for quantification of liver fibrosis and other irregular microscopic objects

OBJECTIVE: To introduce a new mathematical method based on the principles of fractal geometry analysis that permits more realistic quantification of some of the physical (morphologic) aspects of irregular bodies appearing under microscopy. STUDY DESIGN: The principles of the method were tested on microscopic images of irregular collagen deposition in liver tissue. The method uses an ad hoc rectified meter implemented in a computer-assisted planar image analysis system that has been adapted to give metric measures of irregular outlines and surfaces that can be used to produce an index capable of quantifying the typical wrinkledness of biologic objects. Prototypical example measures of liver fibrosis were made on biopsy specimens showing chronic hepatitis C virus-related disease. Measurements were also made of the microscopic images of the abnormal deposition of lipid droplets in hepatocytes, a case of amyloid deposition in an osteoarthromuscular structure and a cytologic specimen of human dendritic cells. RESULTS: The proposed computer-aided method permits rapid measurements of the image of a whole biopsy section digitized at high magnification. The snapshot measurement of liver fibrosis deposition offered by a biopsy pattern is a valid means of more rigorously identifying the staging of the process. CONCLUSION: This method can measure liver fibrosis during chronic liver disease as well as any other irregular biologic structure that cannot be correctly quantified using traditional Euclidean-based metric methodologies.     

Multiple Loci Associated with Renal Function in African Americans

The incidence of chronic kidney disease varies by ethnic group in the USA, with African Americans displaying a two-fold higher rate than European Americans. One of the two defining variables underlying staging of chronic kidney disease is the glomerular filtration rate. Meta-analysis in individuals of European ancestry has identified 23 genetic loci associated with the estimated glomerular filtration rate (eGFR). We conducted a follow-up study of these 23 genetic loci using a population-based sample of 1,018 unrelated admixed African Americans. We included in our follow-up study two variants in APOL1 associated with end-stage kidney disease discovered by admixture mapping in admixed African Americans. To address confounding due to admixture, we estimated local ancestry at each marker and global ancestry. We performed regression analysis stratified by local ancestry and combined the resulting regression estimates across ancestry strata using an inverse variance-weighted fixed effects model. We found that 11 of the 24 loci were significantly associated with eGFR in our sample. The effect size estimates were not significantly different between the subgroups of individuals with two copies of African ancestry vs. two copies of European ancestry for any of the 11 loci. In contrast, allele frequencies were significantly different at 10 of the 11 loci. Collectively, the 11 loci, including four secondary signals revealed by conditional analyses, explained 14.2% of the phenotypic variance in eGFR, in contrast to the 1.4% explained by the 24 loci in individuals of European ancestry. Our findings provide insight into the genetic basis of variation in renal function among admixed African Americans.     

Prognostic Value of Tumor Size in Patients with Remnant Gastric Cancer: Is the Seventh UICC Stage Sufficient for Predicting Prognosis?

Background

The 7th UICC N stage may be unsuitable for remnant gastric cancer (RGC) because the original disease and previous operation usually cause abnormal lymphatic drainage. However, the prognostic significance of the current TNM staging system in RGC has not been studied.

Methods

Prospective data from 153 RGC patients who underwent curative gastrectomy from Jan 1995 to Aug 2009 were reviewed. All patients were classified according to tumor size (<3 cm as N0;>3&≤5 cm as N1;>5&≤7 cm as N2; and>7 cm as N3). The overall survival was estimated using the Kaplan-Meier method, and hazard ratios (HRs) were calculated using the Cox proportional hazard model.

Results

Tumor sizes ranged from 1.0 to 15.0 cm (median 5.0 cm). Tumor size, depth of invasion and lymph node (LN) metastasis were significant prognostic factors based on both the univariate and multivariate analyses (P<0.05). In the survival analysis, the seventh edition UICC-TNM classification provided a detailed classification; however, some subgroups of the UICC-TNM classification did not have significantly different survival rates. The combination of the seventh edition T classification and the suggested N classification, with ideal relative risk (RR) results and P value, was distinctive for subgrouping the survival rates except for the IA versus IB and II A versus IIB. A modified staging system based on tumor size, predicted survival more accurately than the conventional TNM staging system.

Conclusions

In RGCs, tumor size is an independent prognostic factor and a modified TNM system based on tumor size accurately predicts survival.     

Basic endocrinological disorders in chronic renal failure

The aim of this study was to look at basic endocrinological disorders in chronic kidney disease, acquainting endocrinologists with information about the definition and classification of kidney diseases and basic metabolic disorders in uraemia. Secondary hyperparathyroidism, insulin resistance and hyperinsulinism, growth hormone disorders and the possibility of growth hormone treatment, the reasons for and the consequences of hyperprolactinaemia are presented in a practical way. Thyroid hormones management, a problem which requires further study, is portrayed extensively. Hypothalamic-pituitary-adrenal axis disorders are equally complex and not yet fully examined. We have largely concentrated on the practical aspects of diagnostics of the presented disorders.     

Use of DNA methylation for cancer detection and molecular classification

Conjugation of the methyl group at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3' sequence (DNA methylation) is the best studied epigenetic mechanism, which acts together with other epigenetic entities: histone modification, chromatin remodeling and microRNAs to shape the chromatin structure of DNA according to its functional state. The cancer genome is frequently characterized by hypermethylation of specific genes concurrently with an overall decrease in the level of 5-methyl cytosine, the pathological implication of which to the cancerous state has been well established. While the latest genome-wide technologies have been applied to classify and interpret the epigenetic layer of gene regulation in the physiological and disease states, the epigenetic testing has also been seriously explored in clinical practice for early detection, refining tumor staging and predicting disease recurrence. This critique reviews the latest research findings on the use of DNA methylation in cancer diagnosis, prognosis and staging/classification.     

Pancreatic polypeptide in pancreatitis

Pancreatitis is a disease with increasing incidence which can be divided into an acute and a chronic form. In both acute and chronic pancreatitis, changes in plasma concentration of pancreatic polypeptide (PP) and its regulation have been reported. In daily clinical work a serologic test for the precise diagnosis and staging of acute and chronic pancreatitis is still desirable. Therefore, many studies have investigated plasma concentrations of PP in acute and chronic pancreatitis as a diagnostic marker and as a therapeutic option to treat pancreatogenic diabetes mellitus. Although the study results are presently inconclusive and potentially contradictory, the findings are nevertheless encouraging, and indicate that PP might have a role in diagnosis, grading and estimation of the prognosis of pancreatitis. Further data and prospective controlled studies are needed to judge whether PP is of clinical value for diagnosing, staging and predicting long-term outcome in acute and chronic pancreatitis.