Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer.

BackgroundIn 2007, we reported a summary of data comparing diabetic foot complications to cancer. The purpose of this brief report was to refresh this with the best available data as they currently exist. Since that time, more reports have emerged both on cancer mortality and mortality associated with diabetic foot ulcer (DFU), Charcot arthropathy, and diabetes-associated lower extremity amputation.MethodsWe collected data reporting 5-year mortality from studies published following 2007 and calculated a pooled mean. We evaluated data from DFU, Charcot arthropathy and lower extremity amputation. We dichotomized high and low amputation as proximal and distal to the ankle, respectively. This was compared with cancer mortality as reported by the American Cancer Society and the National Cancer Institute.ResultsFive year mortality for Charcot, DFU, minor and major amputations were 29.0, 30.5, 46.2 and 56.6%, respectively. This is compared to 9.0% for breast cancer and 80.0% for lung cancer. 5 year pooled mortality for all reported cancer was 31.0%. Direct costs of care for diabetes in general was $237 billion in 2017. This is compared to$80 billion for cancer in 2015. As up to one-third of the direct costs of care for diabetes may be attributed to the lower extremity, these are also readily comparable.ConclusionDiabetic lower extremity complications remain enormously burdensome. Most notably, DFU and LEA appear to be more than just a marker of poor health. They are independent risk factors associated with premature death. While advances continue to improve outcomes of care for people with DFU and amputation, efforts should be directed at primary prevention as well as those for patients in diabetic foot ulcer remission to maximize ulcer-free, hospital-free and activity-rich days

Discovering and validating disease subtypes for heart failure using unsupervised machine learning methods

Notable heterogeneity exists in the clinical presentation of heart failure (HF) patients. Current subtype classifications are based on ejection fraction may not fully capture the aetiological and prognostic heterogeneity of HF. The use of unsupervised machine learning (ML) approaches, such as cluster analysis, on large-scale observational data from electronic health records (EHR), can enable the discovery of novel subtypes and guide the characterization of their clinical manifestation. Clustering methods can group HF patients based on similarities between their clinical features without making a priori assumptions about the distribution of the data. We sought to discover, characterize and replicate HF subtypes by applying a clustering method on a heterogeneous HF population derived from phenotypically rich EHR. Characterization of HF subtypes using EHR derived variable may enable more precise large-scale genomic analysis to inform better prevention, diagnostic and treatment strategies

Hacking cell differentiation: transcriptional rerouting in reprogramming, lineage infidelity and metaplasia

Initiating neoplastic cell transformation events are of paramount importance for the comprehension of regeneration and vanguard oncogenic processes but are difficult to characterize and frequently clinically overlooked. In epithelia, pre-neoplastic transformation stages are often distinguished by the appearance of phenotypic features of another differentiated tissue, termed metaplasia. In haemato/lymphopoietic malignancies, cell lineage ambiguity is increasingly recorded. Both, metaplasia and biphenotypic leukaemia/lymphoma represent examples of dysregulated cell differentiation that reflect a history of trans-differentiation and/or epigenetic reprogramming. Here we compare the similarity between molecular events of experimental cell trans-differentiation as an emerging therapeutic concept, with lineage confusion, as in metaplasia and dysplasia forecasting tumour development

Preliminary Clinical Results of a Biphasic Waveform and an RV Lead System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72921/1/j.1540-8159.1999.tb00500.x.pd

Testicular cancer and antecedent diseases.

A case-control study of the aetiology of testicular cancer was conducted using information obtained by interview and from case-notes of 259 cases with testicular cancer and two sets of control patients -238 men with diagnoses other than testicular cancer attending the same radiotherapy centres as those attended by the cases, and 251 hospital in-patients not attending radiotherapy departments. Logistic regression analyses were performed, after stratifying by age and region of residence, to estimate the relative risks (RRs) associated with various aspects of prior medical history. The risk of testicular cancer was found to be raised for men with a history of cryptorchidism (RR based on comparison with all controls = 6.3; P less than 0.001), inguinal hernia (RR = 1.6; P = 0.14), mumps orchitis (RR = 12.7; P = 0.006), atopy (RR = 1.8; P = 0.03), and meningitis (RR = 3.0; P = 0.21). Inguinal herniorrhaphy before the age of 15 years was particularly a risk factor for seminoma, whereas the relative risks were similar for seminoma and teratoma for the other factors. The results add to the growing evidence that congenital abnormalities involving the process of testicular descent and closure of the processus vaginalis are risk factors for testicular cancer, and that some types of testicular damage later in life may also be important. The findings of associations with previous atopy and certain infections suggest a possible second aetiological mechanism - that immunological abnormalities may be associated with an increased risk of testis cancer

Prenatal and familial associations of testicular cancer.

In a case-control study of testis cancer 259 cases with testicular cancer, 238 controls treated at radiotherapy centres and 251 non-radiotherapy hospital in-patient controls were interviewed about some possible prenatal and familial risk factors for the tumour. For firstborn men, the risk of testis cancer increased significantly according to maternal age at the subject's birth, and this effect was most marked for seminoma. The association with maternal age was not apparent for cases other than firstborn. The risk of testis cancer was also significantly raised for men from small sibships and of early birth order. These results accord with the theory that raised maternal levels of available oestrogen during the early part of pregnancy are aetiological for testicular cancer in the son, although other explanations are possible; there is evidence that seminoma risk may particularly be affected

Emerging foodborne diseases.

The epidemiology of foodborne diseases is rapidly changing. Recently described pathogens, such as Escherichia coli O157:H7 and the epidemic strain of Salmonella serotype Typhimurium Definitive Type 104 (which is resistant to at least five antimicrobial drugs), have become important public health problems. Well-recognized pathogens, such as Salmonella serotype Enteritidis, have increased in prevalence or become associated with new vehicles. Emergence in foodborne diseases is driven by the same forces as emergence in other infectious diseases: changes in demographic characteristics, human behavior, industry, and technology; the shift toward a global economy; microbial adaptation; and the breakdown in the public health infrastructure. Addressing emerging foodborne diseases will require more sensitive and rapid surveillance, enhanced methods of laboratory identification and subtyping, and effective prevention and control

Mutations in the Amyloid-β Protein Precursor Reduce Mitochondrial Function and Alter Gene Expression Independent of 42-Residue Amyloid-β Peptide

Background:Dominant missense mutations in the amyloid-β protein precursor (AβPP) cause early-onset familial Alzheimer’s disease (FAD) and are associated with changes in the production or properties of the amyloid-β peptide (Aβ), particularly of the 42-residue variant (Aβ42) that deposits in the Alzheimer’s disease (AD) brain. Recent findings, however, show that FAD mutations in AβPP also lead to increased production of longer Aβ variants of 45–49 residues in length. Objective:We aimed to test neurotoxicity of Aβ42 vis-á-vis longer variants, focusing specifically on mitochondrial function, as dysfunctional mitochondria are implicated in the pathogenesis of AD. Methods:We generated SH-SY5Y human neuroblastoma cells stably expressing AβPP mutations that lead to increased production of long Aβ peptides with or without Aβ42. These AβPP-expressing cells were tested for oxygen consumption rates (OCR) under different conditions designed to interrogate mitochondrial function. These cell lines were also examined for expression of genes important for mitochondrial or neuronal structure and function. Results:The mutant AβPP-expressing cells showed decreased basal OCRs as well as decreased OCRs associated with mitochondrial ATP production, even more so in the absence of Aβ42 production. Moreover, mutant AβPP-expressing cells producing longer forms of Aβ displayed altered expression of certain mitochondrial- and neuronal-associated genes, whether or not Aβ42 was produced. Conclusion:These findings suggest that mutant AβPP can cause mitochondrial dysfunction that is associated with long Aβ but not with Aβ42

Campylobacter jejuni--an emerging foodborne pathogen.

Campylobacter jejuni is the most commonly reported bacterial cause of foodborne infection in the United States. Adding to the human and economic costs are chronic sequelae associated with C. jejuni infection--Guillian-Barré syndrome and reactive arthritis. In addition, an increasing proportion of human infections caused by C. jejuni are resistant to antimicrobial therapy. Mishandling of raw poultry and consumption of undercooked poultry are the major risk factors for human campylobacteriosis. Efforts to prevent human illness are needed throughout each link in the food chain

Quantitative Regular Expressions for Arrhythmia Detection Algorithms

Motivated by the problem of verifying the correctness of arrhythmia-detection algorithms, we present a formalization of these algorithms in the language of Quantitative Regular Expressions. QREs are a flexible formal language for specifying complex numerical queries over data streams, with provable runtime and memory consumption guarantees. The medical-device algorithms of interest include peak detection (where a peak in a cardiac signal indicates a heartbeat) and various discriminators, each of which uses a feature of the cardiac signal to distinguish fatal from non-fatal arrhythmias. Expressing these algorithms' desired output in current temporal logics, and implementing them via monitor synthesis, is cumbersome, error-prone, computationally expensive, and sometimes infeasible. In contrast, we show that a range of peak detectors (in both the time and wavelet domains) and various discriminators at the heart of today's arrhythmia-detection devices are easily expressible in QREs. The fact that one formalism (QREs) is used to describe the desired end-to-end operation of an arrhythmia detector opens the way to formal analysis and rigorous testing of these detectors' correctness and performance. Such analysis could alleviate the regulatory burden on device developers when modifying their algorithms. The performance of the peak-detection QREs is demonstrated by running them on real patient data, on which they yield results on par with those provided by a cardiologist.Comment: CMSB 2017: 15th Conference on Computational Methods for Systems Biolog