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Diagnosing disease from the past using historic textual sources can be controversial as to its accuracy. To overcome these objections, an empirical approach to the historical clinical data was developed. The approach follows a standardised, objective, and systematic evaluation, satisfying the requirements of the philosophy of science. Physician-managed medical records of mid-19th century patients reported to have suffered from tuberculosis. A diagnostic algorithm, quantifying clinical data into a scoring system, was developed based on criteria recorded in the medical sources. The findings were compared to the autopsy results using the Receiver Operating Characteristics method. The generated scoring system correctly predicted the diagnosis of tuberculosis in 86% of patients in the study. 6% false negatives and 8% false positives were predicted. It is possible to retrospectively diagnose in a reliable and scientifically robust manner under certain conditions. It is important to embed the clinical data into the historical context. A general rejection of retrospective diagnosis is unsubstantiated. Well-designed, disease-specific, and source adapted medical scoring systems are new approaches and overcome criticism raised against retrospective diagnosis. This new approach utilises diverse historic sources and potentially leads to reliable retrospective diagnosis of most common diseases of the past. Selection bias of the records allocated. Quality of the historic sources utilized. Restricted statistical assessment potential of historic sources. Development of disease- and epoch-specific medical score systems. [ABSTRACT FROM AUTHOR]

The widespread variation in diagnosing primary headache disorders in children and adolescents results in reduced quality and high costs. Defining an algorithm for primary headache diagnoses in children and adolescents is part of a larger initiative to standardize and improve care. The aim of this algorithm was to increase the accuracy of headache diagnosis by formal criteria to more than 80% of patient encounters. A team of headache specialists, nurse practitioners, nurses, data analysts, and business specialists developed an algorithm based on available scientific evidence. This algorithm was vetted and adapted by the neurology faculty and headache specialists until final consensus was reached. Following three months of testing and validation, the algorithm was disseminated to general pediatric neurology clinics. The following information was gathered: percent of encounters utilizing the algorithm, percentage of encounters with appropriate diagnosis by formal criteria, percentage of encounters with appropriate testing ordered, and average cost per headache visit. Correct diagnosis of primary headache by International Classification of Headache Disorders-3 criteria improved from 72% to 90% and appropriate testing improved from 80% to 94%. By the end of analysis, 94% of encounters were correctly implementing the algorithm. A year-long tracking revealed decreased cost of headache evaluation by 6% compared with the year prior. A standardized algorithm improved the diagnostic accuracy in general child neurology clinics. Expanding the algorithm to primary care and pediatric emergency rooms could have a greater impact on headache evaluation and diagnosis; this should result in improved care and outcomes with reduced cost. [ABSTRACT FROM AUTHOR]

Inborn errors of intrinsic and innate immunity constitute the focus of a growing research field that investigates the molecular mechanisms underlying susceptibility to infections previously not considered part of the spectrum of inborn errors of immunity. These so-called nonconventional inborn errors of immunity often occur as infections caused by a narrow spectrum of microorganisms in otherwise healthy subjects. This review aimed to provide a framework for identifying and evaluating patients with viral, bacterial, mycobacterial, and fungal infection needing further assessment for inborn errors of intrinsic and innate immunity. A literature search was performed using PubMed, from inception until 1 May 2022. The search included the following keywords: "inborn errors of immunity"; "inborn errors of innate immunity"; "primary immune deficiency"; "primary immunodeficiency"; "infections"; "infectious susceptibility"; "virus"; "pyogenic bacteria"; "mycobacteria"; "fungi". All article types were considered. We review the definition of what can be considered an inborn error of immunity and how the definition changed over the last ∼25 years. We further provide criteria to rule out secondary immunodeficiencies, identify patients needing further clinical and laboratory immunological assessment, and suspect and diagnose an inborn error of intrinsic and innate immunity. These steps are proposed as part of an algorithm. Patients with unexplained life-threatening infections, including otherwise healthy subjects, should be systematically screened for known inborn errors of immunity. The early diagnosis can prevent recurrence of life-threatening infections in the patients and reduce the total burden of infectious diseases. [ABSTRACT FROM AUTHOR]

Globally, head & neck sarcoma care pathways remain unclear. In 2018, the London Sarcoma Service (LSS) set up a dedicated head and neck sarcoma (HNS) multidisciplinary team (MDT) with a clear objective to provide formal access to super-specialist expertise in diagnosis, treatment planning and management of HNS. The aim of the study is to provide first results of a dedicated HNS MDT. All patients discussed between 2018 and 2022, in HNS MDT, with a new histologically confirmed HNS diagnosis were included in the study. Demographics, anatomic site, morphology, MDT recommendation, treatment details and outcomes were obtained from electronic patient records. A total of 337 patients were discussed in the HNS MDT of which 178 patients were included in the study, with a median age of 53 years(range 2–94); 67 % were soft tissue sarcomas(STS) and 33 % were bone sarcomas(BS), of which 43 % and 71 % were high grade, respectively. 55 % BS and 39 % STS underwent surgery. 9 % of BS and 7 % of STS received adjuvant Proton Beam therapy. With a median follow-up of 2.16 years, recurrence was observed in 12 %, distant metastasis in 6 % of patients and overall survival was 72 %. The HNS MDT provides expertise on diagnosis and multi-modality management of HNS. STS are more likely to be misdiagnosed. Atypical imaging characteristics should trigger a specialist referral. Adequate surgery at first presentation remains the mainstay of treatment and the strongest prognosticator of overall survival. Formation of an expert working group specific to HNS must work towards streamlining sarcoma care. • Transformative Impact: Specialized MDT enhances Head and Neck Sarcoma Care • Optimizing Outcomes: Insights into Delays, Diagnostics, and Treatment Strategies • Integrated Approach: A Diagnostic Algorithm for Improved Patient Survival [ABSTRACT FROM AUTHOR]

Mast cell neoplasms are an emerging challenge in the fields of internal medicine, allergy, immunology, dermatology, laboratory medicine, and pathology. In this review, we discuss the current standards for the diagnosis and prognostication of mast cell neoplasms with special reference to clinically relevant germline and somatic gene variants. In patients with cutaneous mastocytosis or with indolent systemic mastocytosis (SM), various KIT-activating mutations act as key molecular drivers of the disease. In adults, KIT p.D816V is by far the most prevalent driver, whereas other KIT mutants are detected in nearly 40% of children. In advanced SM, including aggressive SM, SM with an associated hematological neoplasm, and mast cell leukemia, additional somatic mutations in other genes, such as SRSF2 , JAK2 , RUNX1 , ASXL1 , or RAS , may be detected. These drivers are more frequently detected in SM with an associated hematological neoplasm, particularly in male patients. Recently, hereditary alpha-tryptasemia has been identified as a genetic trait more prevalent in SM compared with healthy controls. Moreover, hereditary alpha-tryptasemia is more frequent in patients with SM with Hymenoptera venom allergy and severe mediator-related symptoms than in patients with SM without symptoms. On the basis of this knowledge, we propose a diagnostic algorithm in which genetic markers are applied together with clinical and histopathologic criteria to establish the diagnosis and prognosis in SM. [ABSTRACT FROM AUTHOR]

Distinction of hydatidiform moles (HM) from non-molar (NM) specimens and subclassification of HM as complete hydatidiform mole (CHM) versus partial hydatidiform mole (PHM) are important for clinical practice and investigational studies. The issue of diagnostic reproducibility is still unsolved, the lack of diagnostic accuracy based on morphology is substantial with an important interobserver variability, even between experienced gynecologic pathologists. Many ancillary techniques have been investigated in the last years to refine HM diagnosis. p57 (a paternally imprinted, maternally expressed gene) immunohistochemistry, based on the unique genetics of CHM (purely androgenetic), PHM (diandric triploid), and NM specimens (biparental, with allelic balance) can identify CHMs, which lack p57 expression because of a lack of maternal DNA. However, although its role in HM diagnosis is pivotal, it does not allow the distinction of PHM from NM specimens, both of which express p57 due to the presence of maternal DNA. Molecular genotyping, which compares villous and decidual DNA patterns to determine the parental source and ratios of polymorphic alleles, distinguishes purely androgenetic CHM from diandric triploid PHM, and both of these from NM specimens. Beyond the claim of establishing a "diagnostic truth", exceptions and peculiar genetic scenarios in the origin of rare CHM and PHM should be kept in mind when approaching any ancillary technique. An algorithmic approach, even in settings with limited resources, can help the pathologists in the diagnostic dilemma of diagnosis of first trimester abortions. [ABSTRACT FROM AUTHOR]

A single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission. We prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value <3 ng/L was used to rule-out MI. Patients were classified as early (chest pain ≤3 h) or late presenters (>3 h). We included 1370 patients with available admission hs-cTnI results: median (Q1–Q3) age 65 (52–74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0–100%), with both 100% (97.3–100%) for early and 100% (98.2–100%) for late presenters, respectively. Sensitivity was similarly high in the two groups. MI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value <3 ng/L as diagnostic cut-off. NCT03634384. [Display omitted] • A single troponin measurement may be used to rule-out myocardial infarction (MI). • Rule-out of MI was highly safe in late presenters, i.e. presentation >3 h. • Early presenters with MI had lower troponin values than late presenters. • However, rule-out of MI was equally safe in early presenters. • No patients with MI were missed when using a single-testing algorithm at admission. [ABSTRACT FROM AUTHOR]

Objectives: Developing and validating a discrete event simulation model that is able to model patients with heart failure managed with usual care or an early warning system (with or without a diagnostic algorithm) and to account for the impact of individual patient characteristics in their health outcomes.Methods: The model was developed using patient-level data from the Trans-European Network - Home-Care Management System study. It was coded using RStudio Version 1.3.1093 (version 3.6.2.) and validated along the lines of the Assessment of the Validation Status of Health-Economic decision models tool. The model includes 20 patient and disease characteristics and generates 8 different outcomes. Model outcomes were generated for the base-case analysis and used in the model validation.Results: Patients managed with the early warning system, compared with usual care, experienced an average increase of 2.99 outpatient visits and a decrease of 0.02 hospitalizations per year, with a gain of 0.81 life years (0.45 quality-adjusted life years) and increased average total costs of €11 249. Adding a diagnostic algorithm to the early warning system resulted in a 0.92 life year gain (0.57 quality-adjusted life years) and increased average costs of €9680. These patients experienced a decrease of 0.02 outpatient visits and 0.65 hospitalizations per year, while they avoided being hospitalized 0.93 times. The model showed robustness and validity of generated outcomes when comparing them with other models addressing the same problem and with external data.Conclusions: This study developed and validated a unique patient-level simulation model that can be used for simulating a wide range of outcomes for different patient subgroups and treatment scenarios. It provides useful information for guiding research and for developing new treatment options by showing the hypothetical impact of these interventions on a large number of important heart failure outcomes. [ABSTRACT FROM AUTHOR]

Aromatic L-amino acid decarboxylase deficiency is a rare neurometabolic disease due to impaired decarboxylation of neurotransmitter precursors to its active form. Case: We retrospectively reviewed 8 cases from 2008 to 2019 with cerebrospinal fluid neurotransmitter analysis performed at our centre. All cases had an elevated urine vanillactic acid and, in most cases, with N-acetylvanilalanine detected. Cerebrospinal fluid analysis showed low downstream metabolites vanillylmandelic acid, homovanillic acid but high 3-O-methyl-L-DOPA, 5-hydroxytryptophan. Cerebrospinal fluid pterins were normal. Genotyping in DDC confirms the diagnosis. Urine organic acid analysis provided the first clue to diagnosis in four of the cases, which then triggered cerebrospinal fluid neurotransmitter and genetic analysis. We also developed a diagnostic decision support system to assist the interpretation of the mass spectrometry data from urine organic acids. Urine organic acid could be essential in guiding subsequent investigations for the diagnosis of aromatic L-amino acid decarboxylase deficiency. We propose to screen suspected cases first with urine organic acids, specifically looking for vanillactic acid and N-acetylvanilalanine. Suggestive findings should be followed with target analysis for c.714 + 4A > T in ethnically Chinese patients. The assistive tool allowed expedite interpretation of profile data generated from urine organic acids analysis. It may also reduce interpreter's bias when peaks of interest are minor peaks in the spectrum. [ABSTRACT FROM AUTHOR]

Acute coronary syndrome (ACS) is a major cause of death and closely related with obstructive sleep apnea (OSA). Our hypothesis is that several cardiovascular-related biomarkers could have a differential prognostic value for ACS severity in patients with OSA, and could also help (individually or combined) in the detection of OSA in patients after a coronary event. Up to 361 consecutive individuals admitted due to ACS were included in the study. All of them were evaluated for ACS severity (Killip score, number of diseased vessels, ejection fraction) and further classified as OSA or non-OSA. Medical records were registered and eleven blood biomarkers were measured, including heart-type fatty acid-binding globulin, N-terminal pro-brain natriuretic peptide, matrix metalloproteinase-9 (MMP9), placental growth factor (PlGF) and high-sensitivity C-reactive protein. Odds ratios of every biomarker for ACS severity-related parameters were calculated and adjusted for age, gender, body-mass index (BMI), hypertension, diabetes, smoking and drinking. The use of clinical measures and biomarkers for the diagnosis of OSA in ACS patients was evaluated both alone and combined using ROC curves. Several biomarkers showed a significant association with ACS severity, which remained after adjusting for OSA and other potentially confounding variables. The mathematical combination of age, BMI, PlGF and MMP9 showed an area under the ROC curve (AUC) for OSA identification of 0.741, which was greater than any individual parameter or combination assessed: AUC(BMI):0.687, AUC(age):0.576, AUC(PlGF):0.584, AUC(MMP9):0.555. The usefulness of biomarkers in the assessment of ACS severity was independent of OSA and the other variables evaluated. In patients admitted after a coronary event, the combination of clinical measures and biomarkers showed a significant discriminating power for the detection of OSA. Clinical trial registration: NCT01335087 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Abstract Introduction Infections of the sternoclavicular joint (SCJ) account for less than 1% of all joint infections. There are no standardized diagnostic and therapeutic algorithms defined in literature. This study intended to report the risk factors, the bacterial spectrum, the extent and localization and the clinical outcome of SCJ infections. Patients and methods We retrospectively reviewed the medical charts of 13 patients (8 men, five women, mean age 37.6 years) with SCJ infections between Januray 1st 2008 and October 30th 2015 for clinical parameters and radiological studies. All patients were interviewed during their follow-up along with clinical examination and assessing the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH). Results Nine patients presented with local chest pain and swelling; in 4 patients, the prevalent symptom was pain without local signs of inflammation. Full blood count revealed a mean leukocytosis of 15 × 109 L and a mean CRP of 21.0 mg/dl. Approximately 61.5% reported known diabetes mellitus. 10 patients presented an involvement of surrounding structures. All patients received a preoperativ CT scan. Each patient was treated via SCJ resection without intraoperative complications. Primary wound closure was possible in all cases. The mean follow-up was 95 days. Wound culture revealed Staphylococcus aureus in all patients. Pathological examination affirmed acute osteomyelitis in 7 patients. Four patients required the intensive care of which 2 patients died from septic shock. Recurrent infection was encountered in 3 patients who underwent revision surgery. Mean DASH Score was 18.7. Conclusion CT should be routinely obtained to recognize the possible extends to the surrounding structures. SCJ resection can result in satisfactory clinical results and should be considered in cases of extended infections including the surrounding structures. Empiric antibiotic coverage should contain cephalosporin or extended-spectrum penicillin. Inappropriate or less-invasive surgical procedures may cause recurrencent infections, especially in cases of osteomyelitis. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate burden and predictors of HSV pneumonia among immunocompromised patients not undergoing invasive mechanical ventilation according to a tailored diagnostic algorithm.Methods: This prospective, observational study included immunocompromised adults with pneumonia non-responding to empirical antibiotic therapy. Bronchoalveolar lavage (BAL) specimens were cultured for bacteria, mycobacteria and fungi. Real-time PCR for Herpesviruses and other microorganisms were performed on BAL and other specimens. Cytological examination of BAL samples was carried out for identification of intranuclear inclusion bodies and immunohistochemical staining for HSV.Results: We enrolled 45 patients (mean age 64.6 years) from January 2015 to June 2016. Nineteen (42.2%) cases tested positive for HSV-1 PCR on BAL. According to our definitions, 11 (24.4%) patients had HSV-1 pneumonia with viral loads ranging between 103 copies/mL and 107 copies/mL. HSV-1 positive throat swab (OR 85.2, 95% CI 5.83-1245.1, P < 0.001) and solid organ transplant (SOT) (OR 53.3, 95% CI 1.37-2072.8, P < 0.03) as underlying condition were found to be independently associated with HSV pneumonia by multivariable analysis.Conclusions: HSV pneumonia turned out to be relatively common and should be investigated especially in individuals with HSV positive throat swab and SOT. Interventional studies are needed to assess the real clinical impact of HSV pneumonia in immunocompromised patients. [ABSTRACT FROM AUTHOR]

Abstract Mushroom poisoning is a significant and increasing form of toxin-induced-disease. Existing classifications of mushroom poisoning do not include more recently described new syndromes of mushroom poisoning and this can impede the diagnostic process. We reviewed the literature on mushroom poisoning, concentrating on the period since the current major classification published in 1994, to identify all new syndromes of poisoning and organise them into a new integrated classification, supported by a new diagnostic algorithm. New syndromes were eligible for inclusion if there was sufficient detail about both causation and clinical descriptions. Criteria included: identity of mushrooms, clinical profile, epidemiology, and the distinctive features of poisoning in comparison with previously documented syndromes. We propose 6 major groups based on key clinical features relevant in distinguishing between poisoning syndromes. Some clinical features, notably gastrointestinal symptoms, are common to many mushroom poisoning syndromes. Group 1 - Cytotoxic mushroom poisoning. Syndromes with specific major internal organ pathology: (Subgroup 1.1; Primary hepatotoxicity); 1A, primary hepatotoxicity (amatoxins); (Subgroup 1.2; Primary nephrotoxicity); 1B, early primary nephrotoxicity (amino hexadienoic acid; AHDA); 1C, delayed primary nephrotoxicity (orellanines). Group 2 - Neurotoxic mushroom poisoning. Syndromes with primary neurotoxicity: 2A, hallucinogenic mushrooms (psilocybins and related toxins); 2B, autonomic-toxicity mushrooms (muscarines); 2C, CNS-toxicity mushrooms (ibotenic acid/muscimol); 2D, morel neurologic syndrome (Morchella spp.). Group 3 - Myotoxic mushroom poisoning. Syndromes with rhabdomyolysis as the primary feature: 3A, rapid onset (Russula spp.); 3B, delayed onset (Tricholoma spp.). Group 4 – Metabolic, endocrine and related toxicity mushroom poisoning. Syndromes with a variety of clinical presentations affecting metabolic and/or endocrine processes: 4A, GABA-blocking mushroom poisoning (gyromitrins); 4B, disulfiram-like (coprines); 4C, polyporic mushroom poisoning (polyporic acid); 4D, trichothecene mushroom poisoning (Podostroma spp.); 4E, hypoglycaemic mushroom poisoning (Trogia venenata); 4F, hyperprocalcitoninemia mushroom poisoning (Boletus satanas); 4G, pancytopenic mushroom poisoning (Ganoderma neojaponicum). Group 5 - Gastrointestinal irritant mushroom poisoning. This group includes a wide variety of mushrooms that cause gastrointestinal effects without causing other clinically significant effects. Group 6 - Miscellaneous adverse reactions to mushrooms. Syndromes which do not fit within the previous 5 groups: 6A, Shiitake mushroom dermatitis; 6B, erythromelagic mushrooms (Clitocybe acromelagia); 6C, Paxillus syndrome (Paxillus involutus); 6D, encephalopathy syndrome (Pleurocybella porrigens). Highlights • Mushroom poisoning is an increasing problem, with new forms of poisoning described in recent years. • Previous classifications of mushroom poisoning do not reflect the diversity of clinical poisoning now presenting for medical care. • The literature on mushroom poisoning was examined, all new poisoning syndromes tabulated and a new clinical classification devised. • A matrix of clinical effects was used to develop a diagnostic algorithm guiding health professionals in correct diagnosis/treatment. [ABSTRACT FROM AUTHOR]

The newly emerging sinonasal carcinomas have demonstrated diverse morphologies and specific molecular rearrangements along with deviant clinical behavior from conventional counterparts. We aim to propose a diagnostic algorithm that is based on molecular findings of each sinonasal cancer and is considering the new entities has been called upon. Such a diagnostic algorithm should help diagnostic pathologists establish a diagnosis of a challenging sinonasal blue cell carcinomas and researchers performing retrospective analysis of archival cases. Along with consulting our archival cases, literature mining was conducted to retrieve the immunohistochemical and molecular findings regarding the newly emerging entities. Our proposed algorithm distinguishes poorly differentiated (non) keratinizing SNSCC, from anaplastic myoepithelial carcinoma, NUT midline carcinoma, SMARCB1/SMARCA4-deficient teratocarcinosarcoma, SMARCB1/SMARCA4-deficient carcinosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, HPV-related multiphenotypic sinonasal carcinoma and other adenocarcinomas. By incorporating morphologic features, immunohistochemical markers, and molecular investigations, the algorithm enhances the accuracy of diagnosis, particularly in cases where comprehensive molecular testing is not readily available. This algorithm serves as a valuable resource for pathologists, facilitating the proper diagnosis of sinonasal malignancies and guiding appropriate patient management. [ABSTRACT FROM AUTHOR]

Aging and obesity are synergistic sarcopenia risk factors (RF). Their association in sarcopenic obesity (SO) enhances morbidity and mortality, but consensus on SO diagnostic criteria is limited. ESPEN and EASO issued a consensus algorithm for SO screening (obesity and clinical SO suspicion) and diagnosis [low muscle strength by hand-grip (HGS) and low muscle mass by BIA], and we investigated its implementation in older adults (>65-years), as well as SO-associated metabolic RF [insulin resistance (IR: HOMA) and plasma acylated (AG) and unacylated (UnAG) ghrelin, with predictive value also assessed from 5-year-prior observations]. Older adults with obesity from the Italian MoMa study on metabolic syndrome in primary care (n = 76) were studied. 7 of 61 individuals with positive screening had SO (SO+; 9 % of cohort). No individuals with negative screening had SO. SO+ had higher IR, AG and plasma AG/UnAG ratio (p < 0.05 vs negative screening and SO-), and both IR and ghrelin profile predicted 5-year SO risk independent of age, sex and BMI. The current results provide the first ESPEN-EASO algorithm-based investigation of SO in free-living older adults, with 9 % prevalence in those with obesity and 100 % algorithm sensitivity, and they support IR and plasma ghrelin profile as SO risk factors in this setting. [Display omitted] • Consensus on sarcopenic obesity (SO) definition and diagnostic criteria is limited. • ESPEN and EASO recently issued a consensus algorithm for SO screening and diagnosis. • This algorithm is here applied in free-living older adults for the first time. • In this cohort prevalence is 9 % and algorithm is 100 % sensitive for diagnosis. • Insulin resistance and ghrelin profile emerge as SO risk factors in this setting. [ABSTRACT FROM AUTHOR]

A large number of ST-elevation notifications are generated by cardiac monitoring systems, but only a fraction of them is related to the critical condition known as ST-segment elevation myocardial infarction (STEMI) in which the blockage of coronary artery causes ST-segment elevation. Confounders such as acute pericarditis and benign early repolarization create electrocardiographic patterns mimicking STEMI but usually do not benefit from a real-time notification. A STEMI screening algorithm able to recognize those confounders utilizing capabilities of diagnostic ECG algorithms in variation analysis of ST segments helps to avoid triggering a non-actionable ST-elevation notification. However, diagnostic algorithms are generally designed to analyze short ECG snapshots collected in low-noise resting position and hence are susceptible to high levels of noise common in a monitoring environment. We developed a STEMI screening algorithm which performs a real-time signal quality evaluation on the ECG waveform to select the segments with quality high enough for subsequent analysis by a diagnostic ECG algorithm. The STEMI notifications generated by this multi-stage STEMI screening algorithm are significantly fewer than ST-elevation notifications generated by a continuous ST monitoring strategy. [ABSTRACT FROM AUTHOR]

Upper extremity deep vein thrombosis (UEDVT) accounts for 4% to 10% of all cases of deep vein thrombosis. UEDVT may present with localized pain, erythema, and swelling of the arm, but may also be detected incidentally by diagnostic imaging tests performed for other reasons. Prompt and accurate diagnosis is crucial to prevent pulmonary embolism and long-term complications as the post-thrombotic syndrome of the arm. Unlike the diagnostic management of deep vein thrombosis (DVT) of the lower extremities, which is well established, the work-up of patients with clinically suspected UEDVT remains uncertain with limited evidence from studies of small size and poor methodological quality. Currently, only one prospective study evaluated the use of an algorithm, similar to the one used for DVT of the lower extremities, for the diagnostic workup of clinically suspected UEDVT. The algorithm combined clinical probability assessment, D-dimer testing and ultrasonography and appeared to safely and effectively exclude UEDVT. However, before recommending its use in routine clinical practice, external validation of this strategy and improvements of the efficiency are needed, especially in high-risk subgroups in whom the performance of the algorithm appeared to be suboptimal, such as hospitalized or cancer patients. In this review, we critically assess the accuracy and efficacy of current diagnostic tools and provide clinical guidance for the diagnostic management of clinically suspected UEDVT. [ABSTRACT FROM AUTHOR]

Gestational trophoblastic disease (GTD) is a major diagnostic category in gynecological pathology with hydatidiform moles being the most common entities. While the diagnosis of hydatidiform moles fundamentally requires routine histological assessment, it continues to suffer from intra- and inter-observer diagnostic variability, emphasizing the need for new diagnostic modalities. Emerged in recent years as powerful diagnostic methods for accurate classification of hydatidiform moles, p57 immunohistochemistry is highly useful in confirming the diagnosis of complete mole, and PCR-based DNA genotyping has become the gold standard to precisely classify both complete and partial hydatidiform moles. Algorithmic approaches combining traditional histomorphology and these powerful ancillary techniques provide the best diagnostic practice currently available. [ABSTRACT FROM AUTHOR]

Resumen La diarrea crónica es una entidad común en la práctica clínica diaria y supone un deterioro en la calidad de vida de los pacientes. Puede ser el síntoma principal de múltiples etiologías, entre las que se encuentra la malabsorción de ácidos biliares (MAB), que en la población general presenta una prevalencia comparable a la enfermedad celíaca. La MAB ocurre por una alteración en la homeostasis de los ácidos biliares en la circulación enterohepática. Puede aparecer como consecuencia de una disfunción o enfermedad ileal (MAB tipo i ), por causas idiopáticas (MAB tipo ii ) o asociada con otras entidades gastrointestinales (MAB tipo iii ). Entre los diferentes métodos diagnósticos disponibles destacamos la gammagrafía con 75 SeHCAT como gold standard debido a sus valores de sensibilidad, especificidad, seguridad y bajo coste. La principal desventaja es que no se encuentra disponible en todos los países, por lo que se han desarrollado otros métodos como la medición sérica de FGF19 y C4 que, sin embargo, presentan una mayor complejidad y coste. El tratamiento de primera línea ante un diagnóstico de MAB es con quelantes de ácidos biliares como la colestiramina, pero presenta baja tolerabilidad y efectos secundarios, que son menores con los nuevos fármacos como el colesevelam. En resumen, la MAB es una entidad común que se encuentra infradiagnosticada e infratratada, por lo que es fundamental establecer un adecuado algoritmo diagnóstico de la diarrea crónica en el que el estudio con 75 SeHCAT ocuparía la primera o segunda línea en el diagnóstico diferencial de estos pacientes. Chronic diarrhoea is a common entity in daily clinical practice and it leads to a loss in these patients quality of life. It may be the main symptom of multiple ethiologies including bile acid malabsorption (BAM) which has a comparable prevalence to celiac disease. The BAM results from imbalances in the homeostasis of bile acids in the enterohepatic circulation. It can be a consequence of ileal disease or ileal dysfunction (BAM type i ), it can be considered idiopathic or primary (BAM type ii ) or associated with other gastrointestinal entities (BAM type iii ). Among the different diagnostic methods available, 75 SeHCAT study is the primary current method due to its sensitivity, specificity, safety and low cost. The main disadvantage is that it's not available in all countries, so other diagnostic methods have appeared, such as serum measurement of FGF19 and C4, however they are significantly more complex and costly. The first-line treatment of bile acid diarrhoea is bile acid sequestrant, such as cholestyramine, which can be difficult to administer due to its poor tolerability and gastrointestinal side effects. These are less prominent with newer agents such as colesevelam. In summary, the BAM is a common entity underdiagnosed and undertreated, so it is essential to establish a diagnosis algorithm of chronic diarrhoea in which the 75 SeHCAT study would be first or second line in the differential diagnosis of these patients. [ABSTRACT FROM AUTHOR]

Immunological disorders are observed in various clinical presentations in the oral cavity. The pathophysiology of these disorders include but are not limited to primary oral auto-immune disease, systemic disease with oral findings, malignancies, hypersensitivity reactions, drug-induced, and infection-related. Many of these disorders have overlapping oral features, making it difficult for the clinician to diagnose and treat the disorder. There is a need to provide a simple and practical decision-making algorithm to the clinicians and provide them guidance on laboratory investigations. The present review provides a diagnostic algorithm that might minimize outpatient process delays and lead to early management. This is crucial in many cases where oral findings may be the first sign of the disorder, and early treatment can preclude dissemination and complications of the disorder. [ABSTRACT FROM AUTHOR]

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Background: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant.Objective: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules.Study Design: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves.Results: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%.Conclusion: Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally. [ABSTRACT FROM AUTHOR]

Objective The novel high-sensitivity cardiac troponin (hs-cTn) 0 h/1 h-algorithm substantially improves the early triage of patient's assigned “rule-out” or “rule-in” of acute myocardial infarction (AMI), while diagnostic uncertainty remains in that 25–30% of patients assigned to “observe”. We aimed to better characterize these patients. Methods In a prospective multicenter diagnostic study, we applied the hs-cTnT 0 h/1 h-algorithm in 2213 unselected patients presenting with symptoms suggestive of AMI to the emergency department. The final diagnosis was adjudicated by two independent cardiologists using all available information. Survival at 720-days was the prognostic endpoint. Findings were validated using a hs-cTnI 0 h/1 h-algorithm. Results Twenty-four percent (n = 523) of patients were assigned to “observe” by the hs-cTnT 0 h/1 h-algorithm. These patients differed significantly in multiple characteristics from “rule-out” and “rule-in” patients: they were older, in 75% male, and very often (57%) had pre-existing coronary artery disease (CAD). Diagnostic uncertainty for the presence of an AMI/UA was high. Only 39% of patients were suitable for coronary computed tomography angiography (CCTA). The most common final adjudicated diagnoses were non-cardiac disease (38%), non-coronary cardiac disease (24%), unstable angina (UA, 21%), and AMI (15%). Absolute hs-cTnT-changes within 3 h had the highest diagnostic accuracy for AMI (AUC 0.86). Cumulative 720-day survival rate was 86%, which was significantly lower as compared to “rule-out” (p < 0.001) and comparable to “rule-in” (p = ns). Findings were similar for the hs-cTnI “observe” zone. Conclusion “Observe” patients are typically elderly men with pre-existing CAD and high long-term mortality. Absolute hs-cTn-changes within 3 h, functional stress imaging and coronary angiography are the key diagnostic modalities. [ABSTRACT FROM AUTHOR]

Résumé L’allergie alimentaire à l’arachide est une maladie fréquente concernant environ 1 % de la population. Il s’agit d’une allergie potentiellement grave, le plus souvent persistante et ayant un fort impact sur la qualité de vie des patients et de leur entourage. Le diagnostic se fonde sur l’histoire clinique, la réalisation des tests cutanés, la recherche d’IgE spécifiques (IgEs) vis-à-vis de l’arachide et de ses allergènes. Le diagnostic de certitude est établi par la réalisation du test de provocation par voie orale en double insu contre placebo. Sur la base de la revue de la littérature, les auteurs évaluent la place des différents tests dans la démarche diagnostique et proposent un algorithme décisionnel de l’allergie alimentaire à l’arachide. La suspicion du diagnostic est établie sur la base d’une histoire clinique compatible et la positivité du prick-test à l’arachide (native ou extrait). L’algorithme diagnostique s’appuie sur le dosage initial des IgE spécifiques vis-à-vis de rAra h2 et rAra h6 qui, s’il est positif, permet de poser le diagnostic d’allergie alimentaire à l’arachide avec une sensibilité de 98 % et une spécificité de 96 %. En cas de négativité, les dosages des IgEs vis-à-vis de rAra h1 et rAra h3, puis rAra h9 sont justifiés. La présence d’IgEs vis-à-vis de rAra h8 signe l’existence d’une réactivité croisée avec les pollens. Le test de réintroduction orale de l’arachide est réalisé en suivant les recommandations du consensus PRACTALL. Il permet de déterminer le seuil réactogène, d’adapter le régime d’éviction, de suivre l’évolution de l’allergie alimentaire et de définir les modalités d’un protocole d’accoutumance. Allergy due to peanuts is a frequent food allergy, involving about 1% of the population. It is a potentially severe allergy, usually persistent and having a strong impact on the quality of life of the patients and their entourage. The diagnosis is based on the clinical history, the results of skin tests plus serum assays for peanut-specific IgEs and its allergens. Confirmation of the diagnosis is established by a double-blind, placebo-controlled oral provocation test. Based on a review of the literature, we evaluated the place of different tests used in the diagnostic workup and we propose a decisional algorithm for food allergy due to peanuts. The suspicion of this allergy is established on the basis of a compatible clinical history and a positive skin prick-test to peanut (either a real peanut or a peanut extract). The diagnostic algorithm depends on the initial level of IgE specific for rAra h2 and rAra h6, which if positive, establishes the diagnosis of food allergy due to peanuts with a sensibility of 98% and a specificity of 96%. If the results are negative, then IgE assays for rAra h1and rAra h3 and subsequently for rAra h9 are justified. The presence of anti-rAra h8 IgE is a sign of the existence of cross-reactivity with pollens. A repeat oral introduction test may be done, following the PRACTALL consensus recommendations. This allows us to determine the level of reactivity, to implement an avoidance regime, to follow the evolution of the food allergy and to define the details of a dietary regimen. [ABSTRACT FROM AUTHOR]

Multiple recurrent somatic mutations were identified in the majority of patients with myelodysplastic syndromes (MDS), but investigating the broad spectrum of molecular markers in MDS exceeds many laboratories' capacity when traditional molecular techniques are used. High-throughput second generation sequencing (=next-generation sequencing, NGS) has proven to be applicable for comprehensive biomarker mutation analyses allowing to increase diagnostic sensitivity and accuracy and to improve risk stratification and prognostication in addition to cytomorphology and cytogenetic analysis in patients with MDS. Amplicon deep-sequencing enables comprehensive biomarker analysis in a multitude of patients per investigation in an acceptable turn-around time and at affordable costs. Comprehensive myeloid marker panels were successfully introduced into diagnostic practice. Therefore, molecular mutation analysis is ready for use in all patients with suspected MDS, may contribute to risk stratification in possible candidates for allogeneic stem cell transplantation, and should become an integral part of clinical research studies in MDS patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION Gynecomastia is the benign proliferation of the glandular tissue in the male breast. This condition is thought to be caused by the imbalance between estrogen action relative to androgen action at the breast tissue level. Bilateral gynecomastia is frequently found in the neonatal period, early in puberty, and with increasing age. Prepubertal unilateral gynecomastia in the absence of endocrine abnormalities is extremely rare, with only a few cases in literature. PRESENTATION OF CASE We present an otherwise healthy boy of 12 years old with unilateral breast masses. No abnormalities were found on ultrasonography and on all endocrine parameters. Treatment consisted in a new “modified” Webster technique. DISCUSSION The results confirmed validity of this technique in terms of esthetic and functional results, and patient satisfaction. Atypical presentations of gynecomastia are often not recognized. The main pathophysiology of gynecomastia is alteration in the balance between the stimulatory effect of estrogen and the inhibitory effects of androgens on the development of the breast. If there is no causal treatment, surgical resection is the therapy of first choice. CONCLUSION The exact mechanism of unilateral gynecomastia formation in our case is unclear. The evaluation of unilateral gynecomastia can therefore be complex. In conclusion, the surgical treatment of unilateral gynecomastia requires an individual approach, based on an appropriate diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Syncope is a common symptom with many causes. Affecting a large proportion of the population, both young and old, it represents a significant healthcare burden. The diagnostic approach to syncope should be focused on the initial evaluation, which includes a detailed clinical history, physical examination and 12-lead electrocardiogram. Following the initial evaluation, patients should be risk-stratified into high or low-risk groups in order to guide further investigations and management. Patients with high-risk features should be investigated further to exclude significant structural heart disease or arrhythmia. The ideal currently-available investigation should allow ECG recording during a spontaneous episode of syncope, and when this is not possible, an implantable loop recorder may be considered. In the emergency room setting, acute causes of syncope must also be considered including severe cardiovascular compromise due to pulmonary, cardiac or vascular pathology. While not all patients will receive a conclusive diagnosis, risk-stratification in patients to guide appropriate investigations in the context of a diagnostic algorithm should allow a benign prognosis to be maintained. [ABSTRACT FROM AUTHOR]

Abstract: The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders and together are the most common degenerative brain diseases in childhood. They are a group of disorders linked by the characteristic accumulation of abnormal storage material in neurons and other cell types, and a degenerative disease course. All NCLs are characterized by a combination of dementia, epilepsy, and motor decline. For most childhood NCLs, a progressive visual failure is also a core feature. The characteristics of these symptoms can vary and the age at disease onset ranges from birth to young adulthood. Genetic heterogeneity, with fourteen identified NCL genes and wide phenotypic variability render diagnosis difficult. A new NCL classification system based on the affected gene and the age at disease onset allows a precise and practical delineation of an individual patient's NCL type. A diagnostic algorithm to identify each NCL form is presented here. Precise NCL diagnosis is essential not only for genetic counseling, but also for the optimal delivery of care and information sharing with the family and other caregivers. These aspects are challenging because there are also potential long term complications which are specific to NCL type. Therefore care supported by a specifically experienced team of clinicians is recommended. As the underlying pathophysiological mechanism is still unclear for all NCL forms, the development of curative therapies remains difficult. This article is part of a Special Issue entitled: The neuronal ceroid lipofuscinoses or Batten Disease. [Copyright &y& Elsevier]

Abstract: Swine erysipelas is an economically important disease caused by Erysipelothrix rhusiopathiae. Pen-based collection of oral fluids has recently been utilized for monitoring infection dynamics in swine operations. The diagnostic performance of bacterial isolation, real-time PCR, and antibody detection by enzyme-linked immunosorbent assay (ELISA) and fluorescent microbead-based immunoassay (FMIA) methods were evaluated on pen-based oral fluid samples from pigs experimentally infected with E. rhusiopathiae (n =112) and from negative controls (n =32). While real-time PCR was a sensitive method with an overall detection rate of 100% (7/7 pens) one day post inoculation (dpi), E. rhusiopathiae was successfully isolated in only 28.6% (2/7 pens). Anti-Erysipelothrix IgM and IgG antibodies in pen-based oral fluids were detected at 4 to 5 dpi by FMIA and at 5 and 8 dpi by ELISA. The number of infected animals per pen, and in particular the timing of antimicrobial treatment administration impacted bacterial isolation and ELISA results. In oral fluid field samples, E. rhusiopathiae DNA was found in 23.3% of the samples while anti-E. rhusiopathiae IgG and IgM antibodies were found in 59.6% and 5.5% of the samples, respectively. The results suggest that an algorithm integrating oral fluids as specimen and real-time PCR and FMIA as detection methods is effective for earlier detection of an erysipelas outbreak thereby allowing for a more effective treatment outcome. [Copyright &y& Elsevier]

Abstract: Western tourists are increasingly traveling to exotic locations often located in tropical or subtropical regions of the world. The magnitude of international travel and the constantly changing dynamics of arbovirus diseases across the globe demand up-to-date information about arbovirus threats to travelers and the countries they visit. In this review, the current knowledge on arbovirus threats to global travelers is summarized and prioritized per region. Based on most common clinical syndromes, currently known arboviruses can be grouped to develop diagnostic algorithms to support decision-making in diagnostics. This review systematically combines and structures the current knowledge on medically important travel-related arboviruses and illustrates the necessity of a detailed patient history (travel history, symptoms experienced, vaccination history, engaged activities, tick or mosquito bite and use of repellent and onset of symptoms), to guide the diagnosis. [Copyright &y& Elsevier]

Abstract: Background: We previously reported that EGFR mutation-specific antibodies performed well in immunohisto/cytochemical analysis. Assessment of EGFR mutation status for EGFR-TKIs (tyrosin kinase inhibitors) treatment of non-small cell lung cancer (NSCLC) patients can be performed by DNA-based assay. To establish a testing algorithm for EGFR mutation status in NSCLC patients, we utilized the peptide nucleic acid-locked nucleic acid (PNA-LNA) PCR clamp assay to determine the EGFR mutation, and immunostaining to detect the delE746-A750 and L858R mutation protein. Patients and methods: One hundred thirty-three patients with NSCLC were examined by immunostaining with EGFR mutation-specific antibodies, and by the PNA-LNA PCR clamp assay, using histological or cytological samples. The expression levels of immunostaining were classified as positive (score 2+), negative (score 0) or equivocal (score 1+), indicating questionable, negative or weak expression. Of these patients, 42 NSCLC patients received EGFR-TKIs treatment and we analyzed whether expression of mutant EGFR proteins was correlated with progression-free survival in patients with NSCLC treated with EGFR-TKIs. Results: In the 133 samples, positive, negative and equivocal results for EGFR mutation-specific antibodies were observed in 37 patients (27.8%), 85 patients (63.9%) and 11 patients (8.3%), respectively. Thirty-seven patients showed positive EGFR expression by immunostaining, and 35 (94.6%) of these also tested positive in the DNA-based assay. Of 85 EGFR-negative patients by immunostaining, 77 (90.6%) also tested negative in the DNA-based assay. Of the 11 patients with equivocal immunostaining results, DNA-based assay detected EGFR mutation in 8 (72.7%) patients. Immunostaining for the EGFR mutation-specific antibodies showed a sensitivity of 81.4%, specificity of 97.5%, positive predictive value of 94.6% and negative predictive value of 90.6%, excluding the 11 patients with equivocal results. In NSCLC patients treated with EGFR-TKIs, the progression-free survival after the start of EGFR-TKIs treatment was significantly longer in patients with EGFR positive expression than in those with equivocal and negative expression (P =0.002). Conclusions: Our results suggest that patients testing positive for EGFR mutations by immunostaining are good candidates for rapid response EGFR-TKI therapy. Immunostaining for EGFR mutation-specific antibodies is a new test for EGFR-TKI inhibition and could be a useful indicator with regard to patient management. [Copyright &y& Elsevier]

Abstract: Hydatidiform moles represent a fascinating group of trophoblastic proliferative disorders with unique genetic compositions and often challenging morphologic features for diagnosis. While conventional histomorphology remains the cornerstone of the diagnosis of molar gestations, there has been an ongoing search for the past three decades for new diagnostic modalities to aid the pathologist. In this review first we will discuss the histopathologic features of molar gestations and their mimics, including non-molar hydropic abortions, chromosomal trisomy syndromes, digynic non-molar triploidy and placental mesenchymal dysplasia. Then we will focus on the conventional and novel ancillary techniques – ploidy analysis, fluorescent in situ hybridization, immunohistochemistry and molecular genotyping – and their role in the diagnostic algorithm. [Copyright &y& Elsevier]

Abstract: Obscure gastrointestinal hemorrhage is defined as overt or occult bleeding present after normal endoscopic examination of the upper and lower gastrointestinal tracts. Approximately 5% of patients with gastrointestinal hemorrhage can be classified as having obscure bleeding, with most patients found to have responsible lesions in the small intestine. The advent of video capsule endoscopy and deep enteroscopy allows for endoscopic access and therapeutic options in the small intestine. In our current era of cost minimization, reductions in capital equipment expenditures, and a high rate of malpractice claims against clinicians, the decision regarding whether a clinical enterprise should offer small bowel endoscopy using any of the more recent technologies requires an understanding of several factors. This article highlights some of the economic and medicolegal aspects of deep small bowel endoscopy. The following topics will be discussed: costs involved to perform endoscopic imaging of the small bowel; downstream revenue effect resulting from deep enteroscopy; coding, billing, and reimbursement issues; cost-effectiveness studies for diagnostic testing; algorithms for diagnostic evaluation of patients with suspected small bowel pathology; and medicolegal ramifications associated with endoscopic procedures of the small bowel. [Copyright &y& Elsevier]

Background/purpose: To identify genetic expression patterns that can be used to define an appropriate diagnostic algorithm of clinical use in periodontal disease. Materials and methods: Total RNA was extracted from 13 samples corresponding to normal human gingiva {NHG) and human gingiva affected by periodontal disease (PDHG). A comprehensive gene expression analysis was carried out by microarray analysis using Affymetrix Human Genome U133 plus 2.0 oligonucleotide arrays. Results: Sixty-six probe sets (genes and expressed sequence tags - EST) overexpressed in all samples of one of the comparison groups, were used for the diagnostic algorithm. All samples, including an independent test sample, were correctly classified as normal or periodontally affected using the diagnostic algorithm. In addition, 2596 genes/EST were upregulated and 1542 genes/EST were downregulated in PDHG, with numerous gene functions impaired in PDHG, especially those related to the immune response, cell-cell junctions, and extracellular matrix remodeling. Conclusion: Our study reveals differential gene expression profiles in NHG and PDHG. The proposed diagnostic algorithm could have clinical usefulness for differential diagnosis in periodontal disease. [ABSTRACT FROM AUTHOR]

Abstract: The automotive after-sales dealers lack solutions for accurate, comprehensive and efficient fault localization. However, such services in the after-sales networks are crucial to the brand value of automotive manufacturers and for client satisfaction. In this paper, a new approach for the off-board diagnosis is presented, with significant improvements compared to the current technologies. A more robust approach that allows, per the additions of functional modules, to enhance traditional computer aided diagnostic systems towards knowledge based systems that emphasize the whole life cycle of the vehicle. Once the design of a new vehicle has begun, information like the dependencies between the components could be re-used for the models dedicated to the diagnosis task. The massive use of electronics dramatically increases the amount of data to manage for the testing of ECU (Electronic Control Unit) functionalities. The complexity of the sub-systems leads to breakdowns that need qualitative symptom description for fault localization. Finally, a feedback engine completes the expensive models for the diagnosis and returns critical dysfunctions to the design department. In this paper, we present our research on a global modular framework for the diagnosis. It encompasses the needs and requirements of automotive manufacturers. The results are presented with data obtained from low, middle and luxury class vehicles. They demonstrate the performance in real field conditions of our different modules. They are based on the interpretation of observations, the fault localization and isolation and the evaluation of feedbacks for model auto-completion. These experiments show the potential of our proposed approach for the automotive off-board diagnosis task. [Copyright &y& Elsevier]

Abstract: Aim: The presence of specific auto-antibodies in serum (i.e., antinuclear antibodies or ANA, anti-extractable nuclear antigens or anti-ENA, and anti-double stranded DNA or anti-dsDNA ) is one of the major criteria in the diagnostics of Autoimmune Rheumatic Disease. As such, the request for these tests has grown exponentially in laboratory practice. The aim of this study is to describe the implementation of a joint laboratory-clinics guideline for reducing clinically inappropriate requests for autoantibody testing in a broad geographic area (Parma, Modena, Piacenza, Reggio-Emilia) for the diagnosis of Autoimmune Rheumatic Disease. Methods: This study, supported by a Regional grant for innovative research projects started in January 2008, is an observational research aimed at comparing the number of ANA, anti-dsDNA and anti-ENA testing as well as the percentage of positive test results before and after implementation of the diagnostic algorithm in hospitalized patients. A multidisciplinary team consisting of clinical immunologist and laboratory scientists was established, with the aim of collecting and analysing diagnostic criteria, clinical needs, laboratory report formats, analytical procedures, as well as the number of tests performed. The laboratory results and the clinical protocol were both validated by data emerging from the clinical follow-up studies. Results: A joint guideline for auto-antibody testing, placing ANA test at the first level, has been developed and implemented since January 2009. The results for the period January–June 2009 (12,738 tests) were compared with those of the same period in 2008 (13,067 tests). A significant reduction in the number of anti-dsDNA (−26%) and anti-ENA (−15%) was observed. The percentage of second-level tests positivity after implementation of the diagnostic protocol had also consistently increased for both ENA (13% vs 17%) and dsDNA (9% vs 11%). Discussion: The development and implementation of algorithms for the diagnostics of Autoimmune Rheumatic Disease in hospitalized patients was associated with a reduction in the number of second-level tests, but also with an increased diagnostic specificity. This outcome attests that close collaboration and audit between clinicians, laboratory specialists and healthcare services is effective to develop efficient diagnostic algorithms for both hospitalized patients and outpatients. [Copyright &y& Elsevier]

Abstract: The automotive industries lack of solutions for accurately, comprehensively and efficiently fault localization. However, such services in the after-sales networks are crucial to the brand value of automotive manufacturer and for client satisfaction. In this paper, a new approach for the off-board diagnosis is presented, with significant improvements compared to the current technologies usually based on inference rules. A more robust approach that allows, per the additions of functional modules, to enhance traditional computer aided diagnostic systems towards a global diagnostic engine reasoning on different sources of knowledge with their uncertainties. Once the design of a new vehicle has begun, information like the dependencies between the components could be re-used for the models dedicated to the diagnosis task. Moreover, the economic pressure leads to a high degree of innovation with a massive use of electronics in safety, comfort and entertainment (). This dramatically increases the amount of data to manage for the testing of E.C.U. (Electronic Control Unit) functionalities. The complexity of the subsystems leads to breakdowns that need qualitative symptom description for the fault localization. Finally, a feedback engine automatically completes the expensive models for the diagnosis and returns critical dysfunctions to the design department. In this paper, we present our research on a new diagnosis strategy for complex mechatronics systems. It encompasses the needs and requirements of automotive manufacturer. The results are presented with data obtained from low, middle and luxury class vehicles. They demonstrate the performance in real field conditions of our approach. They are based on the interpretation of observations, the fault localization and isolation, the evaluation of feedbacks for model auto-completion. The novelty in this approach is based on the reasoning of different sources of knowledge (construction and design knowledge, expert knowledge, return of experiences) which leads to an efficient diagnosis. The approach approximates the optimal path from the observations toward the fault isolation with the help of a meta-heuristic engine. These experiences show the potential of our proposed approach for the automotive off-board diagnosis task. [Copyright &y& Elsevier]

Abstract: The purpose of this article is to report our practical utilization of dynamic contrast-enhanced magnetic resonance mammography [DCE-MRM] in the diagnosis of breast lesions. In many European centers, was preferred a high-temporal acquisition of both breasts simultaneously in a large FOV. We preferred to scan single breasts, with the aim to combine the analysis of the contrast intake and washout with the morphological evaluation of breast lesions. We followed an interpretation model, based upon a diagnostic algorithm, which combined contrast enhancement with morphological evaluation, in order to increase our confidence in diagnosis. DCE-MRM with our diagnostic algorithm has identified 179 malignant and 41 benign lesions; final outcome has identified 178 malignant and 42 benign lesions, 3 false positives and 2 false negatives. Sensitivity of CE-MRM was 98.3%; specificity, 95.1%; positive predictive value, 98.9%; negative predictive value, 92.8% and accuracy, 97.7%. [Copyright &y& Elsevier]

Abstract: The aims of the present study were to: (1) assess agreement for diagnoses of specific anxiety disorders between direct interviews and the family history method; (2) compare prevalence estimates according to direct interviews and family history information; (3) test strategies to approximate prevalence estimates according to family history reports to those based on direct interviews; (4) test covariates of inter-informant agreement; and (5) test the likelihood of reporting disorders by informants. Analyses were based on family study data which included 1625 distinct informant (first-degree relatives and spouses)–index subject pairs. Our main findings were: (1) inter-informant agreement was satisfactory for panic disorder, agoraphobia, social phobia and obsessive-compulsive disorder; (2) the family history method provided lower prevalence estimates for all anxiety disorders (except for generalized anxiety disorder and obsessive-compulsive disorder) than direct interviews; (3) the lowering of diagnostic thresholds and the combination of multiple family history reports increased the accuracy of prevalence estimates according to the family history method; (4) female gender of index subjects was associated with poor agreement; and (5) informants, who themselves had a history of an anxiety disorder, were more likely to detect this disorder in their relatives which entails the risk of overestimation of the size of familial aggregation. [Copyright &y& Elsevier]

Abstract: We report development of a direct multi-class spectroscopic diagnostic algorithm for discrimination of high-grade cancerous tissue sites from low-grade as well as precancerous and normal squamous tissue sites of human oral cavity. The algorithm was developed making use of the recently formulated theory of total principal component regression (TPCR). The in vivo autofluorescence spectral data acquired from patients screened for neoplasm of oral cavity at the Government Cancer Hospital, Indore, was used to train and validate the algorithm. The diagnostic algorithm based on TPCR was found to provide satisfactory performance in classifying the tissue sites in four different classes – high-grade squamous cell carcinoma, low-grade squamous cell carcinoma, leukoplakia, and normal squamous tissue. The classification accuracy for these four classes was observed to be ∼94%, 100%, 100% and 91% for the training data set (based on leave-one-out cross-validation), and was ∼90%, 90%, 85% and 88%, respectively for the corresponding classes for the independent validation data set. [Copyright &y& Elsevier]

Abstract: The paper reports results of an in vitro study on autofluorescence spectroscopy of fresh and formalin-fixed human breast tissue samples to investigate the effect of formalin fixation on the measured autofluorescence spectra. It also explores the applicability of the approach in discriminating cancerous from the uninvolved sites of the formalin-fixed breast tissues based on their autofluorescence spectra. A probability-based diagnostic algorithm, making use of the theory of relevance vector machine (RVM), a powerful recent approach for statistical pattern recognition, was developed for that purpose. The algorithm provided sensitivity values of up to 97% and specificity values of up to 100% towards cancer for both the independent validation data set as well as for the training data set based on leave-one-out cross-validation. These results suggest that autofluorescence spectroscopy may prove to be a valuable additional in vitro diagnostic modality in clinical pathology setting for discriminating cancerous tissue sites from normal sites. [Copyright &y& Elsevier]

In order to evaluate sensitivity, specificity and accuracy of radiographic findings, 1347 patients with minor cervical injury underwent clinical, orthopaedic, neurosurgical examination, and were classified as monosymptomatic (only cervical pain) or polysymptomatic (cervical pain plus additional symptoms). X-rays were taken in anteroposterior, lateral and open-mouth views; additional views if necessary. X-ray outcome was normal in 69.8% of monosymptomatic patients and there were no fractures. In 45.1% of polysymptomatic patients, outcome was normal, but there were seven fractures. Computed tomography/magnetic resonance (CT/MR) was performed in patients with documented injury and/or strong persistent symptoms. X-ray follow-up at 4–6 weeks included flexion-extension examination. Elevated statistical radiographic values were reached. All patients with minor cervical trauma should undergo clinical, neurosurgical and three-view radiographic follow-up. A simplified algorithm could lead to substantial savings and decrease patients'' exposure to radiation. [Copyright &y& Elsevier]

Evidence-based diagnostic algorithm is highly recommended for the visceral leishmaniasis (VL). This cross-sectional study was performed in Bangladesh to evaluate VL diagnostic tools including serology, buffy coat smear microscopy for LD body and various DNA-based techniques using buffy coat in 100 confirmed VL cases and 100 controls. The performance of tools against spleen smear (gold standard) was evaluated using kappa coefficient. Diagnostic precision and other inherent indicators were considered for index scoring (IS) of performance of tools using factor analysis. A diagnostic algorithm was formulated based on the IS and availability of the tools at different health care facilities of Bangladesh. A high level of agreement (kappa ≥ 0.80) was observed for all the diagnostic tools. The highest kappa coefficients were found for rK39 RDT and rK39 ELISA (0.95), followed by ssuRNA-PCR (0.94), Buffy coat smear (0.93), rK28 ELISA (0.92), rK28 RDT (0.89), LAMP (0.89), Mini-exon PCR (0.86), ITS1 (0.85), and ITS2 PCR (0.80). rK39 RDT was found to be the best diagnostic test (IS: 1.7) followed by rK28 RDT (IS: 1.5), buffy coat smear microscopy (IS: 0.5), rK39 & rK28 ELISA (IS: 0.3), ssuRNA-PCR (IS: ‐0.7) and LAMP, Mini-exon, ITS1, & ITS2 PCR (IS: ‐0.9). rK39 RDT has been proposed as the best option for primary health care facilities, while buffy coat smear microscopy was found to be a good adjunct for confirmation of serology-positive cases and proposed for secondary and tertiary facilities. ssuRNA-PCR or LAMP can be an alternate confirmation tool only applicable to the tertiary facilities. [ABSTRACT FROM AUTHOR]

Background: Severe sepsis and septic shock are still the leading causes of death in Intensive Care Units (ICUs), and timely diagnosis is crucial for treatment outcomes. The progression of electronic medical records (EMR) offers the possibility of storing a large quantity of clinical data that can facilitate the development of artificial intelligence (AI) in medicine. However, several difficulties, such as poor structure and heterogenicity of the raw EMR data, are encountered when introducing AI with ICU data. Labor-intensive work, including manual data entry, personal medical records sorting, and laboratory results interpretation may hinder the progress of AI. In this article, we introduce the developing of an AI algorithm designed for sepsis diagnosis using pre-selected features; and compare the performance of the AI algorithm with SOFA score based diagnostic method.Materials and Methods: This is a prospective open-label cohort study. A specialized EMR, named TED_ICU, was implemented for continuous data recording. One hundred six clinical features relevant to sepsis diagnosis were selected prospectively. A labeling work to allocate SEPSIS or NON_SEPSIS status for each ICU patient was performed by the in-charge intensivist according to SEPSIS-3 criteria, along with the automatic recording of selected features every day by TED_ICU. Afterward, we use de-identified data to develop the AI algorithm. Several machine learning methods were evaluated using 5-fold cross-validation, and XGBoost, a decision-tree based algorithm was adopted for our AI algorithm development due to best performance.Results: The study was conducted between August 2018 and December 2018 for the first stage of analysis. We collected 1588 instances, including 444 SEPSIS and 1144 NON-SEPSIS, from 434 patients. The 434 patients included 259 (59.6%) male patients and 175 female patients. The mean age was 67.6-year-old, and the mean APACHE II score was 13.8. The SEPSIS cohort had a higher SOFA score and increased use of organ support treatment. The AI algorithm was developed with a shuffle method using 80% of the instances for training and 20% for testing. The established AI algorithm achieved the following: accuracy = 82% ± 1%; sensitivity = 65% ± 5%; specificity = 88% ± 2%; precision = 67% ± 3%; and F1 = 0.66 ± 0.02. The area under the receiver operating characteristic curve (AUROC) was approximately 0.89. The SOFA score was used on the same 1588 instances for sepsis diagnosis, and the result was inferior to our AI algorithm (AUROC = 0.596).Conclusion: Using real-time data, collected by EMR, from the ICU daily practice, our AI algorithm established with pre-selected features and XGBoost can provide a timely diagnosis of sepsis with an accuracy greater than 80%. AI algorithm also outperforms the SOFA score in sepsis diagnosis and exhibits practicality as clinicians can deploy appropriate treatment earlier. The early and precise response of this AI algorithm will result in cost reduction, outcome improvement, and benefit for healthcare systems, medical staff, and patients as well. [ABSTRACT FROM AUTHOR]

Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes -borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. [ABSTRACT FROM AUTHOR]

Children suffer a huge and often underappreciated burden of disease in tuberculosis (TB) endemic countries. Major hurdles include limited awareness among health care workers, poor integration of TB into maternal and child health approaches, diagnostic difficulties and a lack of child-friendly treatment options. Accurate disease diagnosis is particularly difficult in young and vulnerable children who tend to develop paucibacillary disease and are unable to produce an expectorated sputum sample. In addition, access to chest radiography is problematic in resource-limited settings. Differentiating between TB exposure and M. tuberculosis infection, and especially between M. tuberculosis infection and TB disease is crucial to guide clinical management. TB represents a dynamic continuum from well-contained "latent" infection to incipient and ultimately severe disease. The clinical spectrum of disease in children is broad and can be confused with a myriad of common infections. We provide a pragmatic 4-step approach to diagnose intra-thoracic TB in children and demonstrate how classifying clinical, radiological and laboratory findings into recognised clinical syndromes may provide a more refined diagnostic approach, even in resource-limited settings. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate clinical outcomes associated with the initiation of treatment for urgency-predominant incontinence in women diagnosed by a simple 3-item questionnaire. Study Design: We conducted a multicenter, double-blinded, 12-week randomized trial of pharmacologic therapy for urgency-predominant incontinence in ambulatory women diagnosed by the simple 3-item questionnaire. Participants (N = 645) were assigned randomly to fesoterodine therapy (4-8 mg daily) or placebo. Urinary incontinence was assessed with the use of voiding diaries; postvoid residual volume was measured after treatment. Results: After 12 weeks, women who had been assigned randomly to fesoterodine therapy reported 0.9 fewer urgency and 1.0 fewer total incontinence episodes/day, compared with placebo (P ≤ .001). Four serious adverse events occurred in each group, none of which was related to treatment. No participant had postvoid residual volume of ≥250 mL after treatment. Conclusion: Among ambulatory women with urgency-predominant incontinence diagnosed with a simple 3-item questionnaire, pharmacologic therapy resulted in a moderate decrease in incontinence frequency without increasing significant urinary retention or serious adverse events, which provides support for a streamlined algorithm for diagnosis and treatment of female urgency-predominant incontinence. [Copyright &y& Elsevier]