scholarly journals CBmeter study: protocol for assessing the predictive value of peripheral chemoreceptor overactivation for metabolic diseases

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e042825
Author(s):  
Marlene Lages ◽  
Lucinda Carvalho ◽  
Salvato Feijó ◽  
Alexandra Vieira ◽  
Rui Fonseca-Pinto ◽  
...  
Keyword(s):  
Predictive Value ◽  
Metabolic Diseases ◽  
Primary Objective ◽  
Metabolic Responses ◽  
Diabetes Diagnosis ◽  
Metabolic Disturbances ◽  
Early Screening ◽  
Peripheral Chemoreceptor ◽  
New Therapeutic Approaches ◽  
Oxygen Administration

IntroductionEarly screening of metabolic diseases is crucial since continued undiagnostic places an ever-increasing burden on healthcare systems. Recent studies suggest a link between overactivated carotid bodies (CB) and the genesis of type 2 diabetes mellitus. The non-invasive assessment of CB activity by measuring ventilatory, cardiac and metabolic responses to challenge tests may have predictive value for metabolic diseases; however, there are no commercially available devices that assess CB activity. The findings of the CBmeter study will clarify the role of the CBs in the genesis of—metabolic diseases and guide the development of new therapeutic approaches for early intervention in metabolic disturbances. Results may also contribute to patient classification and stratification for future CB modulatory interventions.MethodsThis is a non-randomised, multicentric, controlled clinical study. Forty participants (20 control and 20 diabetics) will be recruited from secondary and primary healthcare settings. The primary objective is to establish a new model of early diagnosis of metabolic diseases based on the respiratory and metabolic responses to transient 100% oxygen administration and ingestion of a standardised mixed meal.AnalysisRaw data acquired with the CBmeter will be endorsed against gold standard techniques for heart rate, respiratory rate, oxygen saturation and interstitial glucose quantification and analysed a multivariate analysis software developed specifically for the CBmeter study (CBview). Data will be analysed using clustering analysis and artificial intelligence methods based on unsupervised learning algorithms, to establish the predictive value of diabetes diagnosis.EthicsThe study was approved by the Ethics Committee of the Leiria Hospital Centre. Patients will be asked for written informed consent and data will be coded to ensure the anonymity of data.DisseminationResults will be disseminated through publication in peer-reviewed journals and relevant medical and health conferences.

scholarly journals Vacuum Dynamics as an Alternative Method for Detection of Bimodal Milk Ejection in Dairy Cows

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1860
Author(s):  
Matthias Wieland ◽  
Christina Marie Geary ◽  
Gloria Gioia ◽  
Kerry Lynn Case ◽  
Paolo Moroni ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Predictive Value ◽  
Primary Objective ◽  
Cow Milk ◽  
Kappa Statistics ◽  
Flow Meter ◽  
Flow Curves ◽  
Cross Sectional ◽  
Gold Standard Method ◽  
Milk Flow

The primary objective of our study was to assess the ability of a vacuum recorder to detect the presence of bimodal milk flow curves in dairy cows compared with a portable milk flow meter. In a cross-sectional study, 241 individual cow milking observations were analyzed. We simultaneously collected (1) individual cow vacuum events during milking using portable vacuum recorders, and (2) individual cow milk flow curves by attaching a portable milk flow meter to the same milking unit. Presence of bimodality was assessed with the vacuum recorder visually (BIMVA) and with the gold standard method of a milk flow meter through automatic detection (BIMLA). Kappa statistics revealed moderate agreement between BIMVA and BIMLA [κ, 95% confidence intervals (95% CI) = 0.59 (0.46–0.71)]. Diagnostic test statistics for BIMVA for detection of bimodality indicated moderate performance for sensitivity [0.65 (0.52–0.76)] and positive predictive value [0.71 (0.58–0.82)] and high values for specificity [0.92 (0.87–0.95)] and negative predictive value [0.93 (0.84–0.93)]. We conclude that milking vacuum dynamics are a suitable measure to assess bimodal milk flow curves in dairy cows.

scholarly journals Vasospasm severity is associated with cerebral infarction after subarachnoid hemorrhage

2021 ◽  
Author(s):  
Samuel B Snider ◽  
Ibrahim Migdady ◽  
Sarah L LaRose ◽  
Morgan E Mckeown ◽  
Robert W Regenhardt ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Infarction ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Time Varying ◽  
Single Center ◽  
Early Screening ◽  
Angiographic Vasospasm

AbstractBackgroundThe presence of angiographic vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) is associated with delayed-cerebral ischemia (DCI)-related cerebral infarction and worsened neurological outcome. Transcranial doppler (TCD) measurements of cerebral blood velocity are commonly used after aSAH to screen for vasospasm. We sought to determine whether time-varying TCD measured vasospasm severity is associated with cerebral infarction and to investigate the performance characteristics of different time/severity cutoffs for predicting cerebral infarction.MethodsWe used a retrospective, single-center cohort of consecutive adult aSAH patients with angiographic vasospasm and at least one TCD study. Our primary outcome was DCI-related cerebral infarction, defined as an infarction developing at least 2 days after any surgical intervention without an alternative cause. Time-varying TCD vasospasm severity was defined ordinally (absent, mild, moderate, severe) by the most abnormal vessel on each post-admission hospital day. Cox proportional-hazards models were used to examine associations between time-varying vasospasm severity and infarction. The optimal TCD-based time/severity thresholds for predicting infarction were then identified using the Youden J statistic.ResultsOf 218 aSAH patients with angiographic vasospasm, 27 (12%) developed DCI-related infarction. As compared to those without infarction, patients with infarction had higher modified Fisher scale (mFS) scores, and an earlier onset of more-severe vasospasm. Adjusted for mFS, vasospasm severity was associated with infarction (aHR 1.9, 95% CI: 1.3-2.6). A threshold of at least mild vasospasm severity on hospital day 4 had a negative predictive value of 92% for the development of infarction, but a positive predictive value of 25%.ConclusionsIn aSAH, TCD-measured vasospasm severity is associated with DCI-related infarction. In a single-center dataset, a TCD-based threshold for predicting infarction had a high negative predictive value, supporting its role as an early screening tool to identify at-risk patients.

Carotid Body Chemoreceptors: Physiology, Pathology, and Implications for Health and Disease

2021 ◽  
Author(s):  
Rodrigo Iturriaga ◽  
Julio Alcayaga ◽  
Mark W. Chapleau ◽  
Virend K Somers
Keyword(s):  
Carotid Body ◽  
Metabolic Diseases ◽  
Ionic Channels ◽  
Type I ◽  
Peripheral Chemoreceptor ◽  
Type I Cells ◽  
Obstructive Sleep ◽  
Carotid Body Chemoreceptors ◽  
Respiratory Gases ◽  
I Cells

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2, and pH, eliciting reflex ventilatory, cardiovascular and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiologic responses, and its role in maintaining health and potentiating disease. Emphasis will be placed on: i) Transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ionic channels; ii) Synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; iii) Integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and iv) The contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension and metabolic diseases, and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

Imaging with [99mTc]HMPAO – a novel perspective: investigation of [99mTc]HMPAO leg muscle uptake in metabolic diseases

2021 ◽  
pp. 028418512110636
Author(s):  
Zita Képes ◽  
Márton Mikó ◽  
Kornél Kukuts ◽  
Regina Esze ◽  
Sándor Barna ◽  
...  
Keyword(s):  
Glucose Level ◽  
Metabolic Diseases ◽  
Standardized Uptake Value ◽  
Tracer Uptake ◽  
Metabolic Disturbances ◽  
Perception Threshold ◽  
Vascular Abnormalities ◽  
Leg Muscles ◽  
Hmpao Spect ◽  
99Mtc Hmpao

Background Sensitive imaging modalities in the diagnosis of microcircular complications of the lower extremities induced by metabolic diseases are becoming a focus of interest. Purpose To investigate the [99mTc]HMPAO uptake of the legs in type 2 diabetes mellitus (T2DM) and obesity, and to search for associations with clinical parameters and nerve conducting studies. Material and Methods A total of 57 patients with controlled T2DM and 46 obese participants without DM were enrolled in the study. [99mTc]HMPAO SPECT/CT examinations were performed to evaluate the radiopharmaceutical accumulation of the legs. For the quantitative assessment of tracer uptake, standardized uptake value (SUVpeak) was measured in fixed spheric volumes of interest placed on both sural muscles on the attenuation-corrected images. Measurement of current perception threshold applying Neurometer (NM-01/CPT) was used to evaluate peripheral nerve dysfunction. Laboratory parameters assessing the glucose homeostasis of the study participants were also measured. Results In the diabetic group, significantly lower leg SUV values were detected compared to the non-DM obese group (median: 0.517 vs. 0.607; P < 0.001). Body mass index (BMI) ( P < 0.0001), age ( P = 0.0283), HbA1c ( P = 0.0068), and glucose level ( P = 0.0044) proved to be significant predictors of muscle tracer uptake. Neurometer studies showed positive correlation with HbA1c levels in the T2DM group ( P = 0.0002). Conclusion We assume that [99mTc]HMPAO uptake of leg muscles is associated with microcirculation, so quantitative [99mTc]HMPAO SPECT/CT might be a sensitive method for evaluating lower limb microvascular alterations. BMI, age, HbA1c, and glucose level may be significant predictors of peripheral vascular abnormalities triggered by metabolic disturbances.

Microsatellite Instability as a Predictor of Outcomes in Colorectal Cancer in the Era of Immune-Checkpoint Inhibitors

2021 ◽  
Vol 22 ◽  
Author(s):  
Csongor György Lengyel
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Immune Checkpoint ◽  
Predictive Value ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Primary Objective ◽  
Dna Mismatch ◽  
Dominant Component ◽  
Colon Cancers

: The microsatellite instable phenotype resulting from errors in DNA mismatch repair proteins accounts for as far as 15 to 20% of non-hereditary colon cancers but is scarce in rectal cancer. It has been shown that the increased existence of tumor-specific neoantigens in hypermutated tumors is correlated with higher tumor-infiltrating lymphocytes (TILs) and overexpression of immune checkpoint receptors and ligands, mainly PD-1 and PD-L1. In particular, the data gained up to now gives evidence that neoantigen recognition constitutes a dominant component in the course of immunotherapies. This review's primary objective is to describe current approvals and summarize present knowledge about the outcomes of immuno-oncology treatment of microsatellite instable colorectal cancer (CRC). The secondary objective is to give a narrative report about testing methodologies, prognostics, and the predictive value of microsatellite instability. For this purpose, a literature review was performed, focusing on published clinical trial results, ongoing clinical trials and timelines, testing methods, and prognostic and predictive value of MSI. Following four recent FDA approvals of immunotherapy of MSI-high CRC, further work should be warranted by pathology societies towards standardization and rising concordance and reproducibility across the IHC/MSI testing landscape in order to facilitate professionals to offer better survival options for patients with CRC.

scholarly journals A systematic review of validated suicide outcome classification in observational studies

2019 ◽  
Vol 48 (5) ◽  
pp. 1636-1649 ◽  
Author(s):  
Richard S Swain ◽  
Lockwood G Taylor ◽  
Elisa R Braver ◽  
Wei Liu ◽  
Simone P Pinheiro ◽  
...  
Keyword(s):  
Systematic Review ◽  
Predictive Value ◽  
Chart Review ◽  
Safety Issue ◽  
International Classification Of Diseases ◽  
Epidemiological Studies ◽  
Primary Objective ◽  
Drug Safety Issue ◽  
Vital Records ◽  
Health Care Database

Abstract Background Suicidal outcomes, including ideation, attempt, and completed suicide, are an important drug safety issue, though few epidemiological studies address the accuracy of suicidal outcome ascertainment. Our primary objective was to evaluate validated methods for suicidal outcome classification in electronic health care database studies. Methods We performed a systematic review of PubMed and EMBASE to identify studies that validated methods for suicidal outcome classification published 1 January 1990 to 15 March 2016. Abstracts and full texts were screened by two reviewers using prespecified criteria. Sensitivity, specificity, and predictive value for suicidal outcomes were extracted by two reviewers. Methods followed PRISMA-P guidelines, PROSPERO Protocol: 2016: CRD42016042794. Results We identified 2202 citations, of which 34 validated the accuracy of measuring suicidal outcomes using International Classification of Diseases (ICD) codes or algorithms, chart review or vital records. ICD E-codes (E950-9) for suicide attempt had 2–19% sensitivity, and 83–100% positive predictive value (PPV). ICD algorithms that included events with ‘uncertain’ intent had 4–70% PPV. The three best-performing algorithms had 74–92% PPV, with improved sensitivity compared with E-codes. Read code algorithms had 14–68% sensitivity and 0–56% PPV. Studies estimated 19–80% sensitivity for chart review, and 41–97% sensitivity and 100% PPV for vital records. Conclusions Pharmacoepidemiological studies measuring suicidal outcomes often use methodologies with poor sensitivity or predictive value or both, which may result in underestimation of associations between drugs and suicidal behaviour. Studies should validate outcomes or use a previously validated algorithm with high PPV and acceptable sensitivity in an appropriate population and data source.

Association study of candidate genes with obesity and metabolic traits in antipsychotic-treated patients with first-episode psychosis over a 2-year period

2020 ◽  
Vol 34 (5) ◽  
pp. 514-523 ◽  
Author(s):  
Patricia Gassó ◽  
Joan Albert Arnaiz ◽  
Sergi Mas ◽  
Amalia Lafuente ◽  
Miquel Bioque ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Metabolic Diseases ◽  
Hdl Cholesterol ◽  
Glycated Haemoglobin ◽  
Abdominal Circumference ◽  
First Episode ◽  
Nucleotide Polymorphisms ◽  
Metabolic Disturbances ◽  
Metabolic Traits ◽  
The Impact

Aims: Patients with a first episode of psychosis (FEP) often display different metabolic disturbances even independently of drug therapy. However, antipsychotic (AP) treatment, especially with second-generation APs, is strongly linked to weight gain, which increases patients’ risk of developing obesity and other metabolic diseases. There is an important genetic risk component that can contribute to the appearance of these disturbances. The aim of the present study was to evaluate the effect of polymorphisms in selected candidate genes on obesity and other anthropometric and metabolic traits in 320 AP-treated FEP patients over the course of a 2-year follow-up. Methods: These patients were recruited in the multicentre PEPs study (Phenotype−genotype and environmental interaction; Application of a predictive model in first psychotic episodes). A total of 127 validated single nucleotide polymorphisms (SNPs) in 18 candidate genes were included in the genetic analysis. Results: After Bonferroni correction, SNPs in ADRA2A, FTO, CNR1, DRD2, DRD3, LEPR and BDNF were associated with obesity, abdominal circumference, triglycerides, HDL cholesterol, and/or percentage of glycated haemoglobin. Conclusions: Although our results should be interpreted as exploratory, they support previous evidence of the impact of these candidate genes on obesity and metabolic status. Further research is required to gain a better knowledge of the genetic variants that can be considered relevant metabolic risk factors. The ability to identify FEP patients at higher risk for these metabolic disturbances would enable clinicians to better select and control their AP treatment.

Central dopamine modulates anapyrexia but not hyperventilation induced by hypoxia

2002 ◽  
Vol 92 (3) ◽  
pp. 975-981 ◽  
Author(s):  
Renata C. H. Barros ◽  
Luiz G. S. Branco
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Third Ventricle ◽  
Metabolic Responses ◽  
Intracerebroventricular Injection ◽  
Breathing Frequency ◽  
Peripheral Chemoreceptor ◽  
Hypoxia Exposure ◽  
The Third ◽  
Before And After

Hypoxia causes hyperventilation and decreases body temperature (Tb) and metabolism [O2 consumption (V˙o 2)]. Because dopamine (DA) is released centrally in response to peripheral chemoreceptor stimulation, we tested the hypothesis that central DA mediates the ventilatory, thermal, and metabolic responses to hypoxia. Thus we predicted that injection of haloperidol (a DA D2-receptor antagonist) into the third ventricle would augment hyperventilation and attenuate the drop in Tb and V˙o 2 in conscious rats. We measured ventilation, Tb, andV˙o 2 before and after intracerebroventricular injection of haloperidol or vehicle (5% DMSO in saline), followed by a 30-min period of hypoxia exposure. Haloperidol did not change Tb orV˙o 2 during normoxia; however, breathing frequency was decreased. During hypoxia, haloperidol significantly attenuated the falls in Tb andV˙o 2, although hyperventilation persisted. The present study shows that central DA participates in the thermal and metabolic responses to hypoxia without affecting hyperventilation, showing that DA is not a common mediator of this interaction.

Determinants for Iron Overload-Related Disease in Siblings of Probands with Clinically Detected HFE Hereditary Hemochromatosis: The Hemochromatosis Family Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1857-1857
Author(s):  
Esther M.G. Jacobs ◽  
Jan C.M. Hendriks ◽  
Herman G. Kreeftenberg ◽  
Richard A. de Vries ◽  
Joannes J.M. Marx ◽  
...  
Keyword(s):  
Iron Overload ◽  
Predictive Value ◽  
Serum Iron ◽  
Alcohol Intake ◽  
Hereditary Hemochromatosis ◽  
High Risk Group ◽  
Early Screening ◽  
Related Disease ◽  
Iron Parameters ◽  
And Gender

Abstract The clinical expression of HFE-associated hereditary hemochromatosis (HH) gen is highly variable and may be influenced by nongenetic factors and coinherited genetic modifiers, complicating early screening options to prevent iron-overload related disease. The aim of this study was to verify the existence of HH-related disease in C282Y homozygous siblings of C282Y homozygous probands with clinically detected HFE-related HH and to identify factors predictive for the iron-related disease within these siblings. To this end, C282Y homozygous (n=110, males n=53) and non-homozygous siblings (n=318, males n=145) of 224 probands were compared for levels of serum iron parameters, and self-reported environmental and lifestyle factors and previously diagnosed HH-related diseases. Compared to non-homozygous C282Y siblings, C282Y homozygous siblings more often mentioned to have been diagnosed with arthropathy (Odds Ratio [OR] 2.76, 95% Confidential Interval [CI] 1.71–4.46) and liver disease (OR 2.90, 95%CI 1.27– 6.62). Using multivariate logistic regression modelling, genotype (OR 2.29, 95%CI 1.04– 5.02), age (OR 1.07, 95% CI 1.04–1.09) and gender (OR 1.71, 95%CI 1.04–2.80) were found predictive for the development of iron-associated organ disease. With genotype in the model, there was neither an additive predictive value of the serum iron parameters, nor of body mass index (BMI) or alcohol intake. However, when the predictive value of the iron parameters was analyzed in siblings above 55 yrs, the input of the serum ferritin levels was also significant, with a less prominent influence of gender. In conclusion, our results show that the prevalence of hemochromatosis-attributed morbid conditions is increased in the C282Y homozygous siblings compared to their non-homozygous counterparts. Results furthermore suggest that age and gender, but not BMI and alcohol intake, add to the identification of C282Y homozygous siblings most at risk to develop hemochromatosis-associated disease. These findings will be instrumental in the definition of a high-risk group for iron overload-related disease among siblings of clinically detected C282Y homozygous probands and may contribute to the cost-effectiveness of family screening.

Diagnostic evaluation of immune checkpoint inhibitor (CPI) colitis: The role of CT scan.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 821-821
Author(s):  
Sienna Durbin ◽  
Meghan Mooradian ◽  
Leyre Zubiri ◽  
Ian Matthew Allen ◽  
Florian Fintelmann ◽  
...  
Keyword(s):  
Ct Scan ◽  
Predictive Value ◽  
Gold Standard ◽  
Invasive Procedure ◽  
Primary Objective ◽  
Lower Endoscopy ◽  
Grade 3 ◽  
Sensitivity Specificity ◽  
Tumor Types

821 Background: CPI therapy has expanded rapidly in recent years and represents a major advancement in the treatment of many cancers, including hepatocellular carcinoma, gastric cancer, and colon cancer. However, these therapies are associated with significant toxicities. CPI colitis is one of the most common toxicities and can be fatal, especially when not diagnosed and treated promptly. The current gold standard for diagnosis is endoscopy with biopsy, an invasive procedure that is resource- and time-intensive. CT has emerged as a possible alternative. The primary objective of this study is to identify the diagnostic performance of CT in the evaluation of CPI colitis. Methods: With IRB approval, we conducted a retrospective cohort study of patients who received CPI therapy between 2009-2019 across a single healthcare system. Patients were included if they underwent both abdominal CT and upper/lower endoscopy with biopsy within 72 hours of each other. We reviewed the electronic medical record to identify possible cases of colitis based on either CT or pathology. All cases were labeled as either true positive or false positive based on pathology. We examined clinical characteristics, including CTCAE grade and treatment received. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CT for diagnosing CPI colitis when compared to the gold standard of tissue diagnosis. Results: Of the 4,474 patients screened, 141 met inclusion criteria. Average age was 63 years (23 – 91); 43% were male. Most common tumor types were melanoma (36%) and NSCLC (20%). Seventy-four percent of patients were treated with anti-PD-1/PD-L1 monotherapy. Forty percent had signs of colitis on CT scan and 59% had biopsy-proven CPI colitis. Sensitivity and specificity of CT were 51% and 74%, respectively. PPV of CT was 74% and NPV was 51%. Of those with confirmed CPI colitis, 78% had symptoms that were classified as grade 3 or above. Seventy-three percent received IV steroids and 38% received infliximab. Conclusions: CT demonstrates moderate specificity and PPV and remains an important diagnostic test but does not replace endoscopy/biopsy in the evaluation of CPI colitis.

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