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Alzheimer's disease (AD), a neurodegenerative disorder characterized by progressive cognitive decline, is generally prevalent in elderly people with significant disability and mortality. There is no effective treatment for AD currently, but the early diagnosis might be beneficial for delaying the disease progression. Apart from invasive laboratory tests and expensive neuroimaging examination, the electroencephalography (EEG) and event related potentials (ERPs) have emerged as promising approaches for the early detection of AD as well as mild cognitive impairment (MCI), due to its affordability, noninvasively, and superior temporal resolution. In addition, the recent advent of deep learning architectures further improves the accuracy of AD and MCI diagnosis. This article reviewed the application of EEG signal for the early diagnosis of AD and MCI, especially focusing on ERPs and deep learning. Furthermore, recommendation for further research to recruit the combination of ERP components and deep leaning models in diagnosing AD and MCI was proposed and highlighted.

To evaluate the effect of Urinary albumin creatinine ratio (UACR) on diabetic retinopathy (DR) in People with Type 2 diabetes (T2D) and the cut-off value of UACR for predicting DR using receiver operating characteristic curve (ROC).A prospective cohort study of 2490 people with T2D was conducted with follow-up ranging from 3 to 10 years, with a mean follow-up of 7 years. Dilated fundus examination and urine examination were performed annually. Medical history and clinical data were collected and analyzed. Linear mixed effect models with unstructured variance-covariance were carried out to longitudinally assess the influence of UACR and other factors on DR, and ROC curve was drawn to evaluate the value of UACR in early diagnosis of DR.Linear Mixed-effect models revealed that UACR was positively correlated with the development of DR (β = 0.001, 95 %CI: 1.023-1.241, P lt; 0.001). The area under the ROC curve for UACR was 0.634 (95 %CI: 0.605-0.664, P lt; 0.001), cut-off value for early diagnosis of DR was 27.81 mg/g, the sensitivity was 0.586, and the specificity was 0.632.UACR can predict the occurrence of DR in people with T2D, so it can be considered as a preliminary indicator of DR.

Accurate early diagnosis of a gastrointestinal anastomotic leak remains a challenge. When an anastomotic leak develops, the electrical properties of the tissue undergoing inflammatory processes change, resulting from the extravasation of inflammatory fluid and cellular infiltration. The method described here intends to provide a novel early anastomotic leak warning system based upon measurable changes in tissue impedance nearby an acute inflammatory process.A biodegradable Mg-alloy was compared with a nonabsorbable stainless steel (STS) electrode connected to a wireless recording system for impedance measurement. In vitro measurements were made in physiological solutions and small animal (eight mice) and large animal (eight pigs) models with an anastomotic leak simulated by an open colotomy. Measurements were made at 10 mm intervals from the open colon at baseline and up to 120 min comparing these with a sutured colonic wound and normal tissue.In-vitro biodegradable magnesium electrode impedance evaluation showed good sensitivity to different media due to its environmental corrosion properties. The impedance of an acidic environment (1.06 ± 0.02 kΩ for citric acid) was twice that of phosphate-buffered saline (PBS) (0.64 ± 0.008 kΩ) with a distinction between Normal Saline (0.42 ± 0.013 kΩ) and PBS (0.64 ± 0.008 kΩ). This was in contrast to the performance characteristics of the control STS electrodes, where impedance in an acidic environment was lower than saline or PBS (citric acid:0.76 ± 0.01 kΩ versus PBS: 1.32 ± 0.014 kΩ). In a mouse model simulating an anastomotic leak, there was a significant increase in impedance after 120 min when compared with controls (99.7% increase versus 9.6% increase, respectively; P 0.02). This effect was confirmed in a pig model when relative impedance measurements of the leak and control groups were compared (1.86 ± 0.46 versus 1.07 ± 0.02, respectively; P 0.027).Electrophysiological measurement shows diagnostic sensitivity for a gastrointestinal leak with potential clinical utility in the postoperative detection of early intra-abdominal sepsis. Further investigation of biodegradable tissue sensors capable of monitoring an early anastomotic leak is required.

Although acute mountain sickness (AMS) can be a life-threatening condition, early diagnosis is difficult due to vague and non-specific symptoms. The aim of this study is to investigate biochemical markers that can detect high-altitude diseases in advance. Eight different biomarkers (BNP, HIF-1α, NGAL, MMP-3, MMP-9, SESN2, substance P (SP), and U-II) were studied, and their relationship with AMS was investigated.Of the 84 mountaineers who participated in the mountaineering training organized by the Turkish Mountaineering Federation in the Rize Kaçkar Mountains in 2018, 52 volunteered to participate in the study. Twelve hours after the participants reached an altitude of 2200 m (exposed to moderate hypoxia), their vital parameters were measured, and blood samples were taken for biochemistry tests. Vital signs and Lake Louise (LL) AMS scores were recorded every 24 h during the following 72 h. The participants were divided into two groups according to their LL scores: those with AMS and those without (AMS+ and AMS -), and the vital parameters and biomarker levels of both groups were compared and evaluated.Of the volunteers participating in the study, 35 (67.3%) were male and 17 (32.7%) were female, although there was no gender difference in terms of susceptibility to AMS. Among the investigated markers in the AMS + group, MMP-9 and SP were statistically significantly higher (p = 0.037 and p = 0.038, respectively). There were no statistical differences between AMS- and AMS+ groups with regard to heart rate, oxygen saturation, and systolic and diastolic blood pressure values (p = 0.507, p = 0.929, p = 0.955, p = 0.572, respectively).There were significant differences between the AMS- and AMS+ groups in terms of MMP-9 and SP. However, differences in physical indexes between the groups were not statistically significant. This could provide objective indexes for scanning and screening individuals susceptible to AMS in the early stages of rapid ascending.

International audience; Rasmussen's encephalitis (RE) is a rare chronic inflammatory brain disorder resulting in progressive neurodegeneration in one cerebral hemisphere. The inflammatory process is accompanied by progressive loss of function of the affected hemisphere, associated with drug-resistant partial epilepsy. The diagnosis is based on a range of clinical, electroencephalographic, radiological and biochemical arguments, without any specific formal marker, which makes the diagnosis of the disease complex, especially in its initial phase. Seizures are refractory to anti-seizures medication (ASM) and to classical immunomodulatory treatments. These treatments are also ineffective to stop the degenerative process. Only surgical treatment with hemispherotomy (surgical disconnection of a cerebral hemisphere) allows definitive cessation of seizures but this leads to definitive motor and cognitive deficits. The etiology of RE is not known, but there is strong evidence for an immunopathogenic mechanism involving T-cell mediated immunity. The emergence of biotherapies targeting against various cytokines offers potential therapeutic perspectives. This disease is currently a real challenge in terms of: (i) early diagnosis, before the constitution of marked hemispheric atrophy and the appearance of neurological and cognitive consequences; (ii) recognition of incomplete form; (iii) therapeutic management due to advances in the field of targeted treatment of inflammation; (iv) surgery and recovery possibilities.

Timely diagnosis and treatment of HIV is crucial in HIV-exposed infants to prevent the high rates of mortality seen during the first 2 years of life if HIV is untreated. However, challenges with sample transportation, testing, and result delivery to caregivers have led to long delays in treatment initiation. We aimed to compare the clinical effect of point-of-care HIV testing versus laboratory-based testing (standard of care) in HIV-exposed infants.We did a systematic review and meta-analysis and searched PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Embase, Conference Proceedings Citation Index-Science, and WHO Global Index Medicus, from Jan 1, 2014, to Aug 31, 2020. Studies were included if they pertained to the use of point-of-care nucleic acid testing for infant HIV diagnosis, had a laboratory-based nucleic acid test as the comparator or standard of care against the index test (same-day point-of-care testing), evaluated clinical outcomes when point-of-care testing was used, and included HIV-exposed infants aged younger than 2 years. Studies were excluded if they did not use a laboratory-based comparator, a nucleic acid test that had been approved by a stringent regulatory authority, or diagnostic-accuracy or performance evaluations (eg, no clinical outcomes included). Reviews, non-research letters, commentaries, and editorials were also excluded. The risk of bias was evaluated using the ROBINS-I framework. Data were extracted from published reports. Data from all studies were analysed using frequency statistics to describe the overall populations evaluated and their results. Key outcomes were time to result delivery and antiretroviral therapy initiation, and proportion of HIV-positive infants initiated on antiretroviral therapy within 60 days after sample collection.164 studies were identified by the search and seven were included in the analysis, comprising 37 377 infants in total across 15 countries, including 25 170 (67%) who had point-of-care HIV testing and 12 207 (33%) who had standard-of-care testing. The certainty of evidence was high. Same-day point-of-care testing led to a significantly shorter time between sample collection and result delivery to caregivers compared with standard-of-care testing (median 0 days [95% CI 0-0] vs 35 days [35-37]). Time from sample collection to antiretroviral therapy initiation in infants found to be HIV-positive was significantly lower with point-of-care testing compared with standard of care (median 0 days [95% CI 0-1] vs 40 days [36-44]). When each study's result was weighted equally, 90·3% (95% CI 76·7-96·5) of HIV-positive infants diagnosed using point-of-care testing had started antiretroviral therapy within 60 days of sample collection, compared with only 51·6% (27·1-75·7) who had standard-of-care testing (odds ratio 8·74 [95% CI 6·6-11·6]; p0·0001).Overall, the certainty of the evidence in this analysis was rated as high for the primary outcomes related to result delivery and treatment initiation, with no serious risk of bias, inconsistency, indirectness, or imprecision. In HIV-exposed infants, same-day point-of-care HIV testing was associated with significantly improved time to result delivery, time to antiretroviral therapy initiation, and proportion of HIV-positive infants starting antiretroviral therapy within 60 days compared with standard of care.The BillMelinda Gates Foundation.

(1) To assess the diagnostic accuracy of narrow-band imaging (NBI) in the assessment of benign, premalignant, and malignant vocal fold lesions. (2) To evaluate the diagnostic value of NBI in detection of recurrence in upper aero-digestive tract malignancy.This was a prospective, observational study done between December 2018- November 2019 in the Department of Otolaryngology. One hundred six patients of suspected benign, premalignant, malignant lesions of larynx and hypopharynx along with recurrence cases of upper aerodigestive tract malignancy who have completed chemoradiation therapy. All patients were subjected to white light endoscopy (WLE), NBI, and biopsy for histopathological diagnosis. In WLE, laryngeal lesions were classified into three types: malignant, suspected malignant, and benign. NBI images were classified into 5 types based on the intrapapillary capillary loop (IPCL) patterns: Type I-IV were considered benign and Type V lesion was considered malignant. At the end, WLE and NBI findings were correlated with histopathological reports.The diagnostic accuracy of NBI in diagnosing benign, premalignant, and malignant lesions is significantly better than WLE. The sensitivity of NBI in detecting malignant lesions is significantly greater than WLE. NBI has proved to be of great value in identifying lesions that could be missed by WLE alone, as combined sensitivity of NBI and WLE is significantly higher than WLE alone.NBI is an excellent technique for early detection of laryngopharyngeal malignancies with significantly higher sensitivity than WLE alone.

Although fasciculation on muscle ultrasonography (MUS) is useful in diagnosing amyotrophic lateral sclerosis (ALS), its applicability to early diagnosis remains unclear. We aimed to develop and validate diagnostic models especially beneficial to early-stage ALS via machine learning.We investigated 100 patients with ALS, including 50 with early-stage ALS within 9 months from onset, and 100 without ALS. Fifteen muscles were bilaterally observed for 10 s each and the presence of fasciculations was recorded. Hierarchical clustering and nominal logistic regression, neural network, or ensemble learning were applied to the training cohort comprising the early-stage ALS to develop MUS-based diagnostic models, and they were tested in the validation cohort comprising the later-stage ALS.Fasciculations on MUS in the brainstem or thoracic region had high specificity but limited sensitivities and predictive profiles for diagnosis of ALS. A machine learning-based model comprising eight muscles in the four body regions had a high sensitivity (recall), specificity, and positive predictive value (precision) for both early- and later-stage ALS patients.We developed and validated MUS-fasciculation-based diagnostic models for early- and later-stage ALS.Fasciculation detected in relevant muscles on MUS can contribute to the diagnosis of ALS from the early stage.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal disease and may also present with central nervous system findings at the beginning without specific diagnostic criteria. Brain magnetic resonance imaging (MRI) findings are diverse and can also be diagnostic. We aimed to emphasize the importance of brain MRI findings in the early diagnosis of this fatal disease. Methods: MRI findings, clinical presentations, treatment response, and prognosis of seven patients with HLH were described. Results: There were seven pediatric patients who were initially diagnosed with HLH with neurological findings without systemic signs of HLH: four as primary, two as secondary, and one as possible primary HLH. All patients had contrast-enhancing diffuse cerebellar and brainstem lesions; patchy periventricular and callosal cerebral lesions were observed. Thalamus involvement was found in three (42.8%), corpus callosum involvement in six (85.7%), and cervical spinal involvement in one (14.2%). Patients were followed up with these MRI findings, with prediagnoses of toxic, metabolic, infectious, vascular, and demyelinating diseases. Not all patients met the HLH diagnostic criteria due to incomplete systemic/laboratory findings; therefore, only two were immediately directed for hematopoietic stem cell therapy. Four died shortly after admission, one patient could not be followed up after HLH treatment, and two patients who fulfilled the HLH diagnostic criteria underwent hematopoietic stem cell transplantation and survived. Conclusions: Brain MRI findings, especially in the presence of neurological findings, allow for early diagnosis, which can be life-saving. These common features in brain MRI findings should be evaluated with this suspicion and included in HLH diagnostic criteria.

Pressure injury imposes a significant burden for patients and healthcare systems and the majority of pressure injuries are preventable. The early identification of pressure injury is critical for its prevention. As an objective measure, biomarkers have preliminarily shown the potential to identify individuals at risk for developing pressure injury before it is visually observed to occur. However, these results have not been synthesized.To assess and synthesise the predictive effect of different biomarkers in the early detection of pressure injury formation.A systematic review and meta-analysis.PubMed, EMBASE, CINAHL Complete and the Cochrane Library were comprehensively searched for articles up to June 2021. No restrictions were applied to study design type, language, country, race or date of publication.Two reviewers independently extracted data from all original eligible studies using a specified data extraction form, resolved disagreements through discussion and the involvement of an additional reviewer. Methodological quality of all included studies was independently appraised by two authors with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist and the Newcastle-Ottawa Quality Assessment Scale (NOS). Heterogeneity of each study was estimated using the IEight observational studies involving 10595 participants were included. The overall pooled area under curve (AUC) and the 95% confidence intervals (CIs) of Serum albumin (Alb) was 0.66(0.62-0.70), and the Serum haemoglobin (Hb) was 0.67(0.60-0.74). The AUC and 95% CI of C-reactive protein (CRP) was 0.62(0.50-0.74), Braden score was 0.56 (0.429-0.691), Waterlow score was 0.729(0.654-0.803), Alb with Waterlow was 0.741(0.694-0.787), and the combination of Hb, CRP, Alb, Age and Gender was 0.79(0.682-0.898). Besides, the chemokine interferon-γ-induced protein of 10kd/CXCL10, cytokine interferon-α, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-15 (IL-15) and combination of creatine kinase (CK), myoglobin (Mb), heart-type fatty acid binding protein (H-FABP) and CRP may prove potential for detecting pressure injury.The findings suggest the combination of Hb, CRP, Alb, Age and Gender is superior to other biomarkers. However, the predictive effect of biomarkers needs to be confirmed by more researches and patient-level data.

Background: Patients with Sturge-Weber syndrome type 1 (SWS1) have a port-wine birthmark (PWB) as cutaneous hallmark. Up to 35% of neonates with a high risk PWB develop SWS1. Clinical manifestations are severe and often progressive. Especially early onset seizures are associated with worse neurocognitive outcome. Identification of pre-symptomatic SWS1 patients is hampered because brain MRI in the first months of life does not always show the for SWS1 characteristic leptomeningeal capillary malformation (LMC). Objectives: Identification of sensitive and specific MRI predictors for early SWS1 diagnosis. Methods: In this retrospective single centre study, we included 24 SWS1 patients and 20 controls. We studied specificity and sensitivity for SWS1 diagnosis of LMC and indirect MRI signs such as choroid plexus (CP) size and thickness, abnormal white matter signal, lobar cerebral atrophy, ischemia and cortical calcifications. Results: In SWS1 patients CP thickness and CP thickness ratio on non-contrast brain MRI was significantly increased. The optimal cut-off value of 5.6 mm on the affected side corresponded with a sensitivity of 91.7% and a specificity of 100% for confirmation of SWS1 diagnosis. In 21% of children aged ≤3 months with a later confirmed SWS1 diagnosis, LMC on initial MRI could not be discerned but CP thickness ≥5.6 mm on the affected side confirmed SWS1 diagnosis. Conclusions: In this study, CP size ratio and thickness were found to be sensitive and specific signs additional to earlier described criteria to support SWS1 diagnosis in neonates and infants which need to be confirmed in other series.

Sepsis is a severe and acute disease associated with high mortality, for those who survive, long-term morbidity. In-time detection of pathogen for proper and optimized treatment in the early stage of sepsis is crucial.We performed droplet digital PCR (ddPCR) on two cases of sepsis. The clinical information, laboratory test results, and the therapeutic regimen was detailed recorded.ddPCR showed its clinical value of sepsis ultra-early diagnosis and the guidance of medication in both cases we provided.ddPCR has potential for rapid and precise diagnose in ultra-early stage of sepsis for its high sensitivity and short turn-around-time, thus benefiting in optimal and timely treatment of sepsis.

The onset of schizophrenia is often preceded by a prodromal phase. However, it is difficult to predict the future transition to schizophrenia from the prodromal symptoms. Based on the diagnostic significance of Schneider's first rank symptoms (FRS), especially those representing "ego disorders (Ichstörungen)", we developed a scale of self-alienation-related attributes (Self-A) to assess the psychological characteristics associated with ego disorders for the early diagnosis of schizophrenia.In total, 153 schizophrenia (Sz) patients, 83 at-risk mental state (ARMS) subjects, and 154 healthy control (HC) subjects participated in this study. The Self-A scale was constructed by items from the Minnesota Multiphasic Personality Inventory (MMPI) based on the differences between schizophrenia patients with and without FRS representing ego-disorders designated as "self-alienation symptoms". The Self-A scale was tested for its reliability and validity in a different sample of schizophrenia patients, and was then applied to different cohorts including first-episode schizophrenia (FES) patients, ARMS individuals, and HC subjects.The Self-A consisting of 27 items exhibited good internal consistency reliability. The validity was well demonstrated by the high correlation of the Self-A scores with the self-alienation symptom scores. The ARMS and FES groups had higher Self-A scores than the HC group. The Self-A score in the ARMS individuals who later developed schizophrenia was higher than that in the ARMS subjects who did not, and was comparable with that in the FES group.This study suggests that the newly developed Self-A scale assessing the self-alienation-related attributes can improve the early diagnosis of schizophrenia.

Introduction Idiopathic pulmonary fibrosis (IPF) is progressive and irreversible. Some discrepancies about IPF staging exists, especially in mild phases. Forced vital capacity (FVC) higher than 80% has been considered early or mild IPF even for the design of clinical trials. Methods Spanish multicentre, observational, retrospective study of IPF patients diagnosed between 2012 and 2016, based on the ATS/ERS criteria, which presented FVC greater or equal 80% at diagnosis. Clinical and demographic characteristics, lung function, radiological pattern, treatment, and follow-up were analyzed. Results 225 IPF patients were included, 72.9% were men. The mean age was 69.5 years. The predominant high-resolution computed tomography (HRCT) pattern was consistent usual interstitial pneumonia (UIP) (51.6%). 84.7% of patients presented respiratory symptoms (exertional dyspnea and/or cough) and 33.33% showed oxygen desaturation below 90% in the 6 min walking test (6MWT). Anti-fibrotic treatment was initiated at diagnosis in 55.11% of patients. Median FVC was 89.6% (IQR 17) and 58.7% of patients had a decrease of diffusion lung capacity for carbon monoxide (DLCO) below 60% of theoretical value; most of them presented functional progression (61.4%) and higher mortality at 3 years (20.45%). A statistically significant correlation with the 3-years mortality was observed between DLCO Conclusions Patients with preserved FVC but presenting UIP radiological pattern and moderate–severe DLCO decrease at diagnosis associate an increased risk of progression, death or lung transplantation. Therefore, in these cases, preserved FVC would not be representative of early or mild IPF.

Objective Venous insufficiency is often not readily recognized as a contributing etiology to nonhealing wounds by nonvascular surgery specialists, potentially delaying appropriate treatment to achieve wound healing and increasing healthcare costs. The objective of the present study was to understand the time and resources used before the definitive treatment of venous ulcers. Methods A single-institution retrospective medical record review of C6 patients undergoing radiofrequency saphenous and perforator vein ablation from May 2016 to January 2018 identified 56 patients with 67 diseased limbs. The numbers of inpatient, emergency department, and wound care visits and the intervals to vein ablation from the initial evaluation of the ulceration by a healthcare provider were collected. The demographics, comorbidities, previous venous interventions, wound characteristics, duplex ultrasound imaging, and available wound healing follow-up through July 2018 were assessed for all patients. Results For the 67 limbs examined, 588 total healthcare visits were performed for wound assessment before a referral to a vascular surgeon, with 413 visits at a wound care center (70% of all visits). Other specialty visits included emergency medicine (17.9% of limbs) and rheumatology (22.4% of limbs). Six patients (nine limbs) were admitted to inpatient services for treatment of their ulceration. Overall, the patients were seen an average of 8.6 ± 9.7 times for their ulcer with the wound center before determination of a contributing venous etiology and subsequent treatment. These visits translated to a median of 230 days (interquartile range, 86.5-1088 days) between the first identification of the ulcer by healthcare providers and subsequent accurate diagnosis and definitive treatment of their venous disease with radiofrequency saphenous and perforator vein ablation. After intervention, 18.64% of the limbs had healed at 1 month, 33.92% had healed at 3 months, 50% had healed at 6 months, and 82.92% had healed by 12 months. Conclusions An earlier and accurate diagnosis of the venous contribution to ulcers and subsequent appropriate treatment of venous etiologies in wound formation by a vascular venous specialist could significantly improve healing and minimize resource usage.

Purpose: To investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis. Methods: A retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI. Results: The level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p

Leprosy presents a varied clinical spectrum. Lucius phenomenon is a rare leprosy reaction characterized by erythematous, painful, slightly infiltrated macules and hemorrhagic bullae that progress to ulceration. This case report describes a patient whose diagnosis of leprosy occurred in the presence of Lucius phenomenon. Late diagnosis and delay in the implementation of specific therapy contributed to an unfavorable outcome, highlighting the importance of early identification and treatment of this disease, as well as its complications.

The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

Studies have suggested that qSOFA can be used for early detection of sepsis immediately upon arrival at the emergency department (ED). Despite this, little is known about the risk factors associated with the subsequent diagnosis of sepsis among patients with qSOFA2 in the ED.This is a retrospective cohort study using ED data from a large tertiary medical center in Japan, 2018-2020. We included adult patients (aged ≥18 years) presenting to the ED with suspected infection (e.g., having a fever) and qSOFA2. We identified patients who developed sepsis based on the Sepsis-3 criteria, and compared patient characteristics (e.g., demographics, vital signs upon the initial triage, chief complaint, and comorbidities) between patients who developed sepsis or not. Additionally, we identified the potential risk factors of sepsis among patients with qSOFA2 using a multivariable logistic regression model.We identified 151 (7%) patients who developed sepsis among 2025 adult patients with suspected infection and qSOFA2. Compared with patients who did not develop sepsis, patients who developed sepsis were likely to be older and have vital signs suggestive of imminent sepsis (e.g., high respiratory rate). In the multivariable logistic regression model, the potential risk factors of sepsis among patients with qSOFA2 were older age (adjusted OR, 1.92 [95%CI 1.19-3.19]), vital signs suggestive of imminent sepsis (e.g., adjusted OR of altered mental status, 3.50 [95%CI 2.25-5.50]), receipt of oxygen therapy upon arrival at the ED (adjusted OR, 1.91 [95%CI 1.38-2.26]), chief complaint of sore throat (adjusted OR, 2.15 [95%CI 1.08-4.13]), and the presence of comorbid diabetes mellitus, ischemic heart disease, and chronic kidney disease (e.g., adjusted OR of diabetes mellitus, 1.47 [95%CI 1.10-1.96]). On the contrary, chief complaint of abdominal and chest pain were associated with a lower risk of sepsis (e.g., adjusted OR of abdominal pain, 0.26 [95%CI 0.14-0.45]).We found that older age, vital signs prognosticating sepsis, and the presence of some comorbidities were the potential risk factors of sepsis in patients with qSOFA2. These potential risk factors could be useful to efficiently recognize patients who might develop sepsis in the ED.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

Background More than 3 million cardiovascular implantable electronic devices (CIEDs) are implanted annually. There are minimal data regarding the timing of diagnosis of acute complications after implantation. It remains unclear whether patients can be safely discharged less than 24 hours postimplantation. Objective The purpose of this study was to determine the precise timing of acute complication diagnosis after CIED implantation and optimal timing for same-day discharge. Methods A retrospective cohort analysis of adults 18 years or older who underwent CIED implantation at a large urban quaternary care medical center between June 1, 2015, and March 30, 2020, was performed. Standard of care included overnight observation and chest radiography 6 and 24 hours postprocedure. Medical records were reviewed for the timing of diagnosis of acute complications. Acute complications included pneumothorax, hemothorax, pericardial effusion, lead dislodgment, and implant site hematoma requiring surgical intervention. Results A total of 2421 patients underwent implantation. Pericardial effusion or cardiac tamponade was diagnosed in 13 patients (0.53%), pneumothorax or hemothorax in 19 patients (0.78%), lead dislodgment in 11 patients (0.45%), and hematomas requiring surgical intervention in 5 patients (0.2%). Of the 48 acute complications, 43 (90%) occurred either within 6 hours or more than 24 hours after the procedure. Only 3 acute complications identified between 6 and 24 hours required intervention during the index hospitalization (0.12% of all cases). Conclusion Most acute complications are diagnosed either within the first 6 hours or more than 24 hours after implantation. With rare exception, patients can be considered for discharge after 6 hours of appropriate monitoring.

Background Sellar masses (SM) frequently present with insidious hormonal dysfunction. We previously showed that, by utilizing a combined reflex/reflecting approach involving a laboratory clinician (LC) on common endocrine test results requested by non-specialists, and subsequently adding further warranted tests, previously undiagnosed pituitary disorders can be identified. However, manually employing these strategies by an LC is not feasible for wider screening of pituitary disorders. Objective The aim of this study was to compare the accuracy and financial impact of an Artificial Intelligence (AI) based, fully computerized reflex protocol with manual reflex/reflective intervention protocol led by an LC. Methods We developed a proof-of-concept AI-based framework to fully computerize multi-stage reflex testing protocols for pituitary dysfunction using automated reasoning methods. We compared the efficacy of this AI-based protocol with a reflex/reflective protocol based on manually curated retrospective data in identifying pituitary dysfunction based on 12 months of laboratory testing. Results The AI-based reflex protocol, as compared with the manual protocol, would have identified laboratory tests for add-on that either directly matched or included all manual add-on tests in 92% of cases, and recommended a similar specialist referral in 90% of the cases. The AI-based protocol would have issued 2.8 times the total number of manual add-on laboratory tests at an 85% lower operation cost than the manual protocol when considering marginal test costs, technical staff and specialist salary. Conclusion/Discussion Our AI-based reflex protocol can successfully identify patients with pituitary dysfunction, with lower estimated laboratory cost. Future research will focus on enhancing the protocol’s accuracy and incorporating the AI-based reflex protocol into institutional laboratory and hospital information systems for the detection of undiagnosed pituitary disorders.

Objective To develop an artificial intelligence (AI)–based tool to detect cardiac amyloidosis (CA) from a standard 12-lead electrocardiogram (ECG). Methods We collected 12-lead ECG data from 2541 patients with light chain or transthyretin CA seen at Mayo Clinic between 2000 and 2019. Cases were nearest neighbor matched for age and sex, with 2454 controls. A subset of 2997 (60%) cases and controls were used to train a deep neural network to predict the presence of CA with an internal validation set (n=999; 20%) and a randomly selected holdout testing set (n=999; 20%). We performed experiments using single-lead and 6-lead ECG subsets. Results The area under the receiver operating characteristic curve (AUC) was 0.91 (CI, 0.90 to 0.93), with a positive predictive value for detecting either type of CA of 0.86. By use of a cutoff probability of 0.485 determined by the Youden index, 426 (84%) of the holdout patients with CA were detected by the model. Of the patients with CA and prediagnosis electrocardiographic studies, the AI model successfully predicted the presence of CA more than 6 months before the clinical diagnosis in 59%. The best single-lead model was V5 with an AUC of 0.86 and a precision of 0.78, with other single leads performing similarly. The 6-lead (bipolar leads) model had an AUC of 0.90 and a precision of 0.85. Conclusion An AI-driven ECG model effectively detects CA and may promote early diagnosis of this life-threatening disease.

Background The severe epidemiologic situation of COVID-19 due to the limited capacity of healthcare systems makes it necessary to improve the hospital management and early identification and stratification of patients. The aim of the study was to explore hematological and biochemical parameters at admission to the hospital as novel early predictors for diagnosis with coronavirus disease 2019 (COVID-19) among all suspected patients. Methods This was a retrospective, multicenter, observational study. The clinical data of all suspected patients were analyzed. The suspected patients with negative RT-PCR results were included as the control group, and compared with confirmed patients. Receiver- operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the hematological indexes. Results In total, 326 confirmed COVID-19 patients and 116 control patients were included. The predictive ability of combinations of the hematological and biochemical parameters was significantly superior to that of a single parameter. The area under the ROC curve (AUC) of the aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and the AST to monocyte ratio index (AMRI) were 0.791 and 0.812, respectively. In the multivariate analysis, an ANRI ≥ 6.03(OR: 3.26, 95% CI: 1.02-10.40, P=0.046) and an AMRI ≥ 36.32(OR: 3.64. 95% CI: 1.24-10.68, P=0.02) at admission were independent risk factors related to the occurrence of COVID-19. Conclusions We found two novel predictors with promising predictive capacities for COVID-19 among all suspected patients: ANRI and AMRI. Our findings need to be confirmed in further studies.

Monoclonal gammopathy of renal significance is a clinical–pathological entity grouping renal disorders secondary to the secretion of a monoclonal immunoglobulin synthesized by a B-cell-derived clone and/or plasma cells in a patient with no diagnostic criteria for multiple myeloma. This term applies to a concept recently introduced owing to the need to differentiate this entity from monoclonal gammopathy of undetermined significance, given the negative prognostic impact of its high morbidity and mortality resulting from both renal and systemic involvement, occasionally even progressing to advanced chronic kidney disease. The renal damage occurs via both direct pathogenic mechanisms, with the deposition of the monoclonal protein in different renal structures, as well as indirect mechanisms, acting as an autoantibody provoking dysregulation of the alternative complement pathway. The detection of this monoclonal protein and an early hematologic study are essential, as is the need for a kidney biopsy to establish the associated nephropathological diagnosis. Consequently, this then leads to the start of specific hematologic treatment to detain the production of the monoclonal protein and minimize renal and systemic injury. Resumen: La gammapatía monoclonal de significado renal es una entidad clínico-patológica que agrupa los trastornos renales secundarios a la secreción de una inmunoglobulina monoclonal sintetizada por un clon derivado de células B y/o células plasmáticas en un paciente sin criterios de diagnóstico de mieloma múltiple. Este término se aplica a un concepto introducido recientemente debido a la necesidad de diferenciar esta entidad de la gammapatía monoclonal de significado incierto, teniendo en cuenta el impacto pronóstico negativo de su alta morbilidad y mortalidad a causa de la afectación tanto renal como sistémica, llegando en ocasiones a progresar a una enfermedad renal crónica avanzada. El daño renal se produce tanto por mecanismos patogénicos directos, con el depósito de la proteína monoclonal en diferentes estructuras renales, como por mecanismos indirectos, actuando como un autoanticuerpo que provoca la desregulación de la vía alternativa del complemento. La detección de esta proteína monoclonal y un estudio hematológico precoz son imprescindibles, así como la necesidad de una biopsia renal para establecer el diagnóstico nefropatológico asociado. En consecuencia, esto lleva al inicio de un tratamiento hematológico específico para detener la síntesis de la proteína monoclonal y minimizar la lesión renal y sistémica.

The rupture of an unstable atherosclerotic plaque is one of the major causes of thrombosis. However, there was limited evidence on the relationship of triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, with the carotid plaque stability. This study aimed to investigate the association between the TyG index and carotid plaque stability in nondiabetic adults.The study included 4748 nondiabetic participants from the Asymptomatic Polyvascular Abnormalities Community study. Carotid plaque stability was assessed using ultrasonography. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Logistic regression was used to evaluate the association of the TyG index with carotid plaque stability by calculating odds ratio (OR) and 95% confidence interval (CI). Of the 4748 participants, 1192 (25.11%) participants had stable carotid plaque, and 1247 (26.26%) had unstable carotid plaque. The prevalence of unstable carotid plaque substantially increased with increasing TyG index tertile (P for trend0.0001). In the fully adjusted model, the OR comparing participants in the highest versus the lowest tertile of the TyG index was 1.31 (95% CI, 1.09-1.57). The optimal cutoff point for the TyG index in case of unstable carotid plaque was 8.56. However, we did not observe a statistically significant association between the TyG index and stable carotid plaque.Elevated the TyG index was significantly associated with the prevalence of unstable carotid plaque in nondiabetic adults.

Proximal urea cycle disorders (PUCDs) are not included in most newborn screening programs due to the lack of adequate markers to monitor. Failure to alter citrulline and glutamine levels, the prognostic markers commonly used, can results in high false negative. Therefore, new biomarkers, prognostic of PUCDs, are strongly desirable.We used tandem mass spectrometry to analyze blood spot from PUCDs patients during their follow up in our referral center focusing on glutamine to glutamate (Gln/Glu) ratio. We reanalyzed the same specimens of three patients after two months and the specimen of a new patient with suspicious of PUCD disorder.Specimens of our patients shown a significant elevation of the ratio Gln/Glu compared to that of a healthy population (p 0.05) as well as the specimens analyzed after two months, while the glutamine concentration dropped. New patient, showing high value of the ratio, was molecularly confirmed as PUCD patient. We further analyzed the blood spots from a neonatal population in order to fix a cut-off value and include it in a newborn screening panel.Our preliminary results suggest that the Gln/Glu ratio could be a very useful diagnostic marker, more stable over time than glutamine, which could improve the performance in early PUCDs identification.

Objectives To elaborate an ECG-based nomogram estimating the probability to detect cardiac involvement by cardiac magnetic resonance (CMR) in Fabry Disease (FD). Methods 119 FD patients and 26 healthy controls underwent ECG and CMR. Test (n = 88, 60%) and validation cohorts (n = 57, 40%) were randomly derived. Cardiac involvement was defined as the presence of low myocardial T1 value, a CMR-surrogate of myocardial glycosphingolipid storage. ECG changes associated with low T1 value were identified in the test cohort, included in the nomogram and then tested in the validation cohort. Results Sokolow-Lyon index (AUC = 0.769), ratio between P-wave and PR-segment durations (Pwave/PRsegment) (AUC = 0.778), QRS duration (AUC = 0.703), QT (AUC = 0.769) duration were independently associated with the presence of low T1 on CMR at multivariate analysis. An ECG-based nomogram including these four parameters was accurate in identifying patients with CMR evidence of glycosphingolipid storage (c-index of the derived-nomogram = 0.90 in the test group; 0.81 in the validation group). Conclusion We propose a practical ECG-based nomogram accurately estimating the probability to detect low T1 values by CMR in FD patients. The application of this tool in clinical practice could improve early detection of FD cardiac involvement.

Summary Background Self-reported symptoms during the COVID-19 pandemic have been used to train artificial intelligence models to identify possible infection foci. To date, these models have only considered the culmination or peak of symptoms, which is not suitable for the early detection of infection. We aimed to estimate the probability of an individual being infected with SARS-CoV-2 on the basis of early self-reported symptoms to enable timely self-isolation and urgent testing. Methods In this large-scale, prospective, epidemiological surveillance study, we used prospective, observational, longitudinal, self-reported data from participants in the UK on 19 symptoms over 3 days after symptoms onset and COVID-19 PCR test results extracted from the COVID-19 Symptom Study mobile phone app. We divided the study population into a training set (those who reported symptoms between April 29, 2020, and Oct 15, 2020) and a test set (those who reported symptoms between Oct 16, 2020, and Nov 30, 2020), and used three models to analyse the self-reported symptoms: the UK's National Health Service (NHS) algorithm, logistic regression, and the hierarchical Gaussian process model we designed to account for several important variables (eg, specific COVID-19 symptoms, comorbidities, and clinical information). Model performance to predict COVID-19 positivity was compared in terms of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) in the test set. For the hierarchical Gaussian process model, we also evaluated the relevance of symptoms in the early detection of COVID-19 in population subgroups stratified according to occupation, sex, age, and body-mass index. Findings The training set comprised 182 991 participants and the test set comprised 15 049 participants. When trained on 3 days of self-reported symptoms, the hierarchical Gaussian process model had a higher prediction AUC (0·80 [95% CI 0·80–0·81]) than did the logistic regression model (0·74 [0·74–0·75]) and the NHS algorithm (0·67 [0·67–0·67]). AUCs for all models increased with the number of days of self-reported symptoms, but were still high for the hierarchical Gaussian process model at day 1 (0·73 [95% CI 0·73–0·74]) and day 2 (0·79 [0·78–0·79]). At day 3, the hierarchical Gaussian process model also had a significantly higher sensitivity, but a non-statistically lower specificity, than did the two other models. The hierarchical Gaussian process model also identified different sets of relevant features to detect COVID-19 between younger and older subgroups, and between health-care workers and non-health-care workers. When used during different pandemic periods, the model was robust to changes in populations. Interpretation Early detection of SARS-CoV-2 infection is feasible with our model. Such early detection is crucial to contain the spread of COVID-19 and efficiently allocate medical resources. Funding ZOE, the UK Government Department of Health and Social Care, the Wellcome Trust, the UK Engineering and Physical Sciences Research Council, the UK National Institute for Health Research, the UK Medical Research Council, the British Heart Foundation, the Alzheimer's Society, the Chronic Disease Research Foundation, and the Massachusetts Consortium on Pathogen Readiness.

Aims a) To analyze the relationship of known and emerging biomarkers/indicators for early risk identification of cardiometabolic health risk; b) to identify early risk markers to be used in both clinical and nonclinical settings; and c) to propose a definition of early risk identification in terms of pre-metabolic syndrome (PreMetSyn). Data synthesis Pubmed/Medline, Web of Science, Embase, and Cochrane were searched for Systematic Reviews and Meta-analysis. Selected studies were evaluated, and relevant data were extracted and synthesized. Conclusions Serum uric acid is a good predictive biomarker of metabolic syndrome (MetSyn) and has been associated with non-alcoholic liver fat disease (NAFLD) and type 2 diabetes. NAFLD emerges as an early risk indicator of PreMetSyn by itself. Muscle strength should also be included as an early risk marker of cardiometabolic health. High serum triglycerides and waist circumference confirm their predictive value regarding MetSyn. Indicators related to an inflammatory/pro-inflammatory status usually linked to MetSyn showed limited evidence as robust biomarkers for PreMetSyn. Authors suggest defining PreMetSyn related to cardiometabolic risk. It is also necessary to determine how close people are to the cut-off point of MetSyn components, including emerging indicators proposed by our review. Some biomarkers could be used as indicators of PreMetSyn, before any of the MetSyn components appear, allowing early health interventions to prevent its development. Defining a PreMetSyn status might consider both emerging indicators and those variables already included in the definition of MetSyn. New indicators should be considered to create a new risk score specifically meant for PreMetSyn.

The COVID-19 pandemic has entailed simultaneous revolutions in virology diagnostics, clinical trials management, and antiviral therapy and vaccinology. Over the past year, SARS-CoV-2 diagnostic testing has moved from highly centralized laboratories to at-home and even over the-counter. This transition has been lionized for its potential public health impact via isolation, but has been less examined for its effect on individual health and therapeutics. Since early initiation of antiviral therapy routinely has been associated with greater treatment efficacy for viral infections, these diagnostic testing innovations offer new opportunities for both clinical testing as well as clinical trials for antiviral therapy. Given a rapidly growing antiviral therapeutic pipeline and the profound impact of individual beneficiary outcomes on sculpting reimbursement policy, the therapeutic benefits associated with rapid viral testing may lead to significant adoption beyond potential public health impacts.

Background Pertussis, is an infectious respiratory disease caused by Bordetella pertussis. The incidence of pertussis has been increasing in South Korea to due to waning vaccine-induced immunity. Culture has a low sensitivity and a long turnaround time (TAT). Recently, a rapid multi-polymerase chain reaction (mPCR) test with a TAT of about 1 h was developed for the detection of respiratory pathogens (17 viruses and three bacteria), including B. pertussis. This study aimed to investigate the effectiveness of mPCR for early diagnosis and treatment of pertussis. Methods We performed a retrospective study of patients with pertussis diagnosed from May 2017 to June 2019 at a university hospital in South Korea. Nasopharyngeal swab specimens were tested using mPCR. Data were extracted from medical records. Results A total of 27 patients with a median age of 48.9 years (range: 3.3–82.2 years) were diagnosed with pertussis, of whom 9 (33.3%) were male. Eleven (40.7%) had fever, 12 (44.4%) had dyspnea, three (11.1%) had paroxysmal cough, and nine (33.3%) had inspiratory whooping. The median interval from symptom onset to diagnosis was 9.0 days (range: 1–31 days). Twenty-four patients (81.5%) were diagnosed within 2 weeks from symptom onset. All but one patient was prescribed macrolide antibiotics. Twenty-two patients (81.5%) required hospitalization, including three (11.1%) who required intensive care unit care for ventilation. Conclusion Testing patients with respiratory symptoms using mPCR can improve early diagnosis of pertussis, ensure proper treatment, and may help with outbreak control.

Major depressive disorder (MDD) is the most common mood disorder, and causes various mental, physical and cognitive symptoms. Clinicians diagnose MDD using multiple interviews and overall impression during the interviews, which makes MDD diagnosis highly subjective. To overcome this, we investigated novel protein biomarker for MDD. Serum from each subject were analyzed using nano liquid chromatography-triple time-of-flight mass spectrometry. We identified two proteins, zinc-alpha-2-glycoprotein (ZA2G) and keratin type II cytoskeletal 1 (K2C1), as final biomarkers. These biomarkers were downregulated during depression (p 0.05, AUC of ROC0.7). ZA2G is related to tryptophan metabolism, which is a main serotonin synthesis pathway. K2C1 is involved in the kinin-kallikrein system, which produces bradykinin, an anti-inflammatory mediator in the brain. Our results suggest that the two protein candidates are related to inflammation and that MDD is highly associated with inflammation. Finally, since all subjects in the two groups were taking antidepressants, our results suggest that the identified biomarkers could determine the presence or absence of illness and could be used to monitor therapeutic effects.

Despite more than two million pediatric operations performed in the United States annually, normal postoperative recovery remains difficult to define. Wearable sensors that assess physical activity and vital signs in real time represent a tool to assess postoperative recovery. This study examined the use of a wearable, the FitBit Inspire HR, to describe recovery in children after appendectomy and to determine the sensitivity of wearable data to distinguish disease severity.Children 3-18 y old undergoing appendectomy in a tertiary children's hospital were invited to participate. Participants wore the FitBit Inpire HR after surgery for 21 d. t-tests compared daily step counts, and piecewise linear regression models were fit to examine recovery trajectories for patients with simple and complicated appendicitis.Thirty-two patients were enrolled, and 26 met eligibility criteria. Nine (35%) children had complicated appendicitis, and 14 (54%) were female; the mean age was 9.1 y (standard deviation: 2.9). Four hundred nineteen postoperative days were captured (range: 8-22 d; median: 16 d). Step counts increased after surgery; however, piecewise models showed that patients with simple appendicitis had a more rapid increase (P 0.01) and reached a plateau (approximately 8000 steps/d) on postoperative day 9, whereas patients with complicated appendicitis did not reach a plateau and had lower step counts during the entire 21-postoperative day period (P 0.01).Recovery in children after surgery can be characterized using wearables, which can also distinguish recovery trajectories based on disease severity. Establishing such "normative" recovery patterns may lead to earlier detection of complications.

Objective The aim of the present study was to gain insight into the pathophysiology of diabetic polyneuropathy (DPN) and examine the diagnostic value of sensory and motor axonal excitability testing. Methods One hundred and eleven type 2 diabetics with and without DPN (disease duration: 6.36 ± 0.25 years) and 60 controls were included. All participants received a thorough clinical examination including Michigan Neuropathy Screening Instrument (MNSI) score, nerve conduction studies (NCS), and sensory and motor excitability tests. Patients were compared by the likelihood of neuropathy presence, ranging from no DPN (17), possible/probable DPN (46) to NCS-confirmed DPN (48). Results Motor excitability tests showed differences in rheobase and depolarizing threshold electrotonus measures between NCS-confirmed DPN group and controls but no changes in hyperpolarising threshold electrotonus or recovery cycle parameters. Sensory excitability showed even less changes despite pronounced sensory NCS abnormalities. There were only weak correlations between the above motor excitability parameters and clinical scores. Conclusions Changes in excitability in the examined patient group were subtle, perhaps because of the relatively short disease duration. Significance Less pronounced excitability changes than NCS suggest that axonal excitability testing is not of diagnostic value for early DPN and does not provide information on the mechanisms.

Transport workers like seafarers, truck-, bus-, train- and taxi drivers and fishers have a known great inequity in health at work including high risk of developing type 2 diabetes. Their routine mandatory medical examinations use urine glucose for diabetes check with more than 50% false negatives, which should be replaced by high sensitive tests for diabetes-2, like A1C, Fasting Glucose (FPG) or Oral Glucose Tolerance Test (OGTT).

Gonococcal meningitis is an exceedingly rare infectious disease, and if not diagnosed and treated in time, it can be severe. We present a case of gonococcal meningitis occurring in a 31-year old healthy woman. She was admitted with fever and persistent headache without urogenital symptoms. Blood cultures were positive and identified as N.gonorrhoeae, but CSF and cervical secretions cultures were both negative. Further testing confirmed the presence of N.gonorrhoeae by 16S ribosomal gene amplification and sequencing in all samples. These results suggest that the case may be a disseminated infection caused by untreated gonorrhea. Our case also shows that nucleic acid detection plays an important role in the rapid and precise diagnosis of gonococcal meningitis and in finding the origin of the pathogen.

Background Purpose To evaluate Pentacam and OPD-Scan parameters in the early detection of keratoconus. Design Retrospective case-control study. Methods Case group included 50 clinically unaffected fellow eyes diagnosed with asymmetric keratoconus showing subtle qualitative changes at the 0.5-D sensitivity OPD-Scan scale, as well as normal anterior and back elevation difference map at Belin/Ambrosio enhanced ectasia display (BAD) at the Pentacam. Control group included 172 normal eyes that underwent Lasik surgery and presented no complications throughout the 2-year follow-up period. OPD-Scan and Pentacam parameters were compared, calculating sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A multivariate analysis was performed using Pentacam or OPD-Scan variables, and a model using variables of both devices. Results Pentacam variables with AUC ≥0.8 were keratoconus index (0.85), index of height decentration (0.81), and overall deviation at BAD (0.8). OPD-Scan variables with AUC ≥0.8 were keratoconus prediction index (0.83), surface asymmetry index (0.83), and total of higher-order trefoil aberration (0.8). In the multivariate analysis, the AUC was 0.85 in the case of OPD-Scan whereas it was 0.89 in the case of Pentacam. When combining all variables from the 2 devices, the AUC was 0.93, with a sensitivity of 82% and a specificity of 94%. Conclusions Several parameters of OPD-Scan and Pentacam can be useful to differentiate cases from normal control eyes, demonstrating even better results when combining parameters of both devices. Anterior corneal indexes were the most important parameters to discriminate both groups.

Purpose Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. In recent years, machine learning methods have been widely used on analysis of neuroimage for quantitative evaluation and computer-aided diagnosis of AD or prediction on the conversion from mild cognitive impairment (MCI) to AD. In this study, we aimed to develop a new deep learning method to detect or predict AD in an efficient way. Materials and methods We proposed a densely connected convolution neural network with connection-wise attention mechanism to learn the multi-level features of brain MR images for AD classification. We used the densely connected neural network to extract multi-scale features from pre-processed images, and connection-wise attention mechanism was applied to combine connections among features from different layers to hierarchically transform the MR images into more compact high-level features. Furthermore, we extended the convolution operation to 3D to capture the spatial information of MRI. The features extracted from each 3D convolution layer were integrated with features from all preceding layers with different attention, and were finally used for classification. Our method was evaluated on the baseline MRI of 968 subjects from ADNI database to discriminate (1) AD versus healthy subjects, (2) MCI converters versus healthy subjects, and (3) MCI converters versus non-converters. Results The proposed method achieved 97.35% accuracy for distinguishing AD patients from healthy control, 87.82% for MCI converters against healthy control, and 78.79% for MCI converters against non-converters. Compared with some neural networks and methods reported in recent studies, the classification performance of our proposed algorithm was among the top ranks and improved in discriminating MCI subjects who were in high risks of conversion to AD. Conclusions Deep learning techniques provide a powerful tool to explore minute but intricate characteristics in MR images which may facilitate early diagnosis and prediction of AD.

BACKGROUND: The Wisconsin Cystic Fibrosis Neonatal Screening Project was a randomized clinical trial (RCT) revealing that children receiving an early diagnosis of CF via newborn screening (NBS) had improved nutritional outcomes but similar lung disease severity compared to those who presented clinically. Because the evaluations of these subjects by protocol ended in 2012, our objective was to assess long-term pulmonary and mortality outcomes. METHODS: Retrospective analysis of the RCT cohort utilized longitudinal outcome measures obtained from the Cystic Fibrosis Foundation Patient Registry (CFFPR). Data included screening assignment, clinical characteristics, percent predicted forced expiratory volume in 1 second (ppFEV(1)) and mortality. A random intercept model was used to compare the ppFEV(1) decline of subjects between the two groups up to age 26 years. Mortality was analyzed using the Kaplan-Meier method. RESULTS: Of the 145 subjects who consented to the original study, 104 subjects met inclusion criteria and had adequate data in the CFFPR. Of 57 subjects in the screened group and 47 in the control group, the rates of ppFEV(1) decline were 1.76%/year (95% CI 1.62 to 1.91%) and 1.43%/year (95% CI 1.26 to 1.60%), respectively (p

Background and aims In-stent restenosis (ISR) remains the most daunting challenge of current treatments of coronary artery disease (CAD). MicroRNAs (miRNAs) are prominent regulators of key pathological processes leading to restenosis and used as diagnostic tools in different studies. miR-152 and miR-148a are implicated to contribute in the putative intracellular mechanisms of ISR. The aim of present study is to investigate the potential early-stage diagnostic role of miR-152 and miR-148a expression levels for ISR in peripheral blood mononuclear cells (PBMCs) of patients who underwent stent implantation. Methods and results The miRNAs that are supposed to be involved in the ISR were nominated by bioinformatics approach mainly using miRWalk3. Then by quantitative real-time PCR, we determined the relative expression of miR-152 and miR-148a of PBMCs from ISR patients with their age/sex-matched controls. Results The presence of ISR significantly coincided with a decrease in the relative expression of miR-152. The area under the curve (AUC) for miR-152 receiver operating characteristic (ROC) curve was 0.717 (95% CI; 0.60–0.83) with a sensitivity of 70% and a specificity of 67%, suggesting that the miRNA expression level might be employed to identify patients at risk of ISR. Conclusions To the best of our knowledge, this is the first work to show that the miR-152 expression level can possibly be applied to predict CAD patients at risk of ISR. The results suggest that the expression levels of miR-152 in PBMCs may serve as a biomarker for ISR. Our finding suggests the importance of miRNA levels in PBMCs as a novel biological tool to detect diseases in their early clinical stages.

Vertical transmission of Trypanosomacruzi is the cause of congenital Chagas disease, a re-emerging infectious disease that affects endemic and nonendemic regions alike. An early diagnosis is crucial because prompt treatment achieves a high cure rate, precluding evolution to symptomatic chronic Chagas disease. However, early diagnosis involves low-sensitive parasitologic assays, making necessary serologic confirmation after 9 months of life. With the aim of implementing early diagnostic strategies suitable for minimally equipped laboratories, a T. cruzi-loop-mediated isothermal amplification (LAMP) prototype was coupled with an automated DNA-extraction device repurposed from a three-dimensional printer (PrintrLab). The whole process takes3 hours to yield a result, with an analytical sensitivity of 0.1 to 2 parasite equivalents per milliliter, depending on the T. cruzi strain. Twenty-five blood samples from neonates born to seropositive mothers were tested blindly. In comparison to quantitative real-time PCR, the PrintrLab-LAMP dual strategy showed high agreement, while both molecular-based methodologies yielded optimal sensitivity and specificity with respect to microscopy-based diagnosis of congenital Chagas disease. PrintrLab-LAMP detected all 10 congenitally transmitted T. cruzi infections, showing promise for point-of-care early diagnosis of congenital Chagas disease.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) classically initially present with ventricular arrhythmias or, less commonly, heart failure. Myocardial inflammation has been implicated in pathogenesis, but clinical myocarditis in ARVC is less described. We therefore studied clinical myocarditis as an initial ARVC presentation, and hypothesized that these patients have distinct clinical and genetic characteristics. Using the Johns Hopkins ARVC Registry, we identified 12 patients (all female, median age 20) referred between 2014 and 2019 diagnosed with myocarditis at presentation who were subsequently diagnosed with ARVC by Task Force Criteria. Majority presented with chest pain (n = 7, 58%) or ventricular arrhythmia (n = 3, 25%). All patients had troponin elevations and left ventricular (LV) function was reduced in 5 (42%). Magnetic resonance imaging demonstrated LV delayed gadolinium enhancement and/or pericardial enhancement in 10 (83%); only 3 (25%) patients had right ventricular abnormalities. Pathogenic genetic variants were identified in 11 (92%) patients: 10 desmoplakin (DSP) and 1 desmoglein-2 (DSG2). Thus, nearly 1/3 (10/32, 31%) of overall DSP ARVC patients were originally diagnosed with myocarditis. Patients were diagnosed with ARVC 1.8 years (IQR 2.7 years) after presentation and 8 (75%) patients did not meet Task Force Criteria without genetic testing. ARVC diagnosis led to an additional 5 (42%) patients referred for implantable cardiac defibrillator and 17 family member diagnoses. In conclusion, ARVC may initially present as myocarditis and these patients have distinct characteristics including female gender, LV involvement and DSP gene variants. Genetic testing is key to ARVC diagnosis and should be considered in select myocarditis patients.

Summary There is no abstract for this commissioned commentary for OAC special issue, and shall not be.

PURPOSE: To test the hypothesis that a recently proposed pattern standard deviation (PSD) metric, based upon the 24–2 visual field (VF) test, as well as the PSD of the 10–2 VF, will miss central glaucomatous damage confirmed with an objective structure-function method. DESIGN: Cross-sectional study METHODS: A glaucoma (G) group (70 eyes/patients) diagnosed as glaucoma, with a 24–2 mean deviation better than −6 dB, and a healthy (H) group (45 eyes/patients) had 24–2 and 10–2 VFs, and optical coherence tomography (OCT) scans twice within 4 weeks. The PSD (C24–2), based upon the central 12 points of the 24–2, was compared to the PSD(10–2). To evaluate central damage (CD) in G eyes with normal PSD(C24–2) values, a post hoc analysis was combined with a reference standard for central damage (CD-RS), which was based upon an objective, topographical comparison between abnormal points on the 10–2 VF and OCT probability maps. RESULTS: The 115 PSD(C24–2) and PSD(10–2) values were significantly correlated (Spearman’s CC: rho = 0.55; p < 0.001) and the number of G eyes, 19, identified as abnormal by the PSD(C24–2) was not significantly different from the number, 22, identified by the PSD(10–2) (P=0.15). However, based upon the CD-RS, 44 of the 70 G eyes were classified as abnormal. The PSD(C24–2) missed 27 (61%) of these 44 eyes, and the PSD(10–2) missed 23 (52%). Post-hoc analysis revealed clear central damage in most of these eyes. CONCLUSION: Neither the PSD(C24–2) nor the PSD(10–2) metric is good measure of early central damage. Instead we recommend a topographical approach based upon OCT probability maps, and a 10–2 VF.

Objective: To modify the current neural tube defect (NTD) classification for fetal medicine specialists, and to investigate the impact of prenatal ultrasound conus medullaris position screening on the detection rate of closed spinal dysraphism and pregnancy outcomes. Materials and methods: The clinical data of 112 patients prenatally diagnosed with neural tube defects in Taiji clinic from 2008 to 2018 were retrospectively analyzed. All cases were classified following the modified classification. We compared the detection rate before and after introducing the conus medullaris screening and pregnancy outcomes for NTD types. Results: Closed spinal dysraphism type prevailed in our sample (43.8%). The median gestational age at the time of detection for cranial dysraphism was 13.3 weeks, open spinal dysraphism was 22.0 weeks, and closed spinal dysraphism was 22.6 weeks. All cranial dysraphism (n = 43) and open spinal dysraphism cases (n = 20) had pregnancies terminated. For closed spinal dysraphism Class 1, the live-birth rate was 100.0% in the cases without other anomalies and 33.3% in the cases with other anomalies, respectively (X2 = 17.25, p

Retinoblastoma is the most common ocular malignancy of childhood. With an estimated 300 cases annually in the United States, retinoblastoma is nevertheless considered a rare tumor. Although retinoblastoma primarily affects younger children, diagnosis during the neonatal age range is less common. However, an understanding of patients at risk is critical for appropriate screening. Early detection and treatment by a multidisciplinary specialty team maximizes the chance for survival and ocular/vision salvage while minimizing treatment-related toxicity. Testing for alterations in the RB1 gene has become standard practice, and informs screening and genetic counseling recommendations for patients and their families.