Establishing Reference Intervals for Serum and Salivary Cortisol in a Selected Population in Kano, Nigeria.

OBJECTIVE: Serum cortisol has long been used in the assessment of disorders of the hypothalamic-pituitary-adrenal axis. The reference interval for cortisol in both serum and saliva depends on the analytical methodology and the population studied; hence, a locally derived population-based reference interval is recommended. To our knowledge, there are no studies on reference interval determination in the study area, raising concerns about the use of reference intervals established in European and North American populations. This work aimed to establish reference intervals for baseline serum and salivary cortisol levels among healthy adults in Kano, Nigeria, using methods available in our laboratory. METHODS: A cross-section of 148 apparently healthy reference individuals aged 16 to 67 years were recruited from a local community in Kano, Nigeria, using a systematic sampling technique. Baseline serum cortisol was analyzed using highly sensitive and specific electrochemiluminescence quantitative measurements on an automated immunology analyzer. Salivary cortisol levels were measured using Salimetrics' competitive enzyme-linked immunosorbent assay test kits. Parametric methods with a 95% confidence interval were used to calculate reference intervals. RESULTS: The reference intervals for cortisol in serum and saliva were 72.0 nmo/L to 554.0 nmol/L and 0.40 nmol/L to 18.0 nmol/L, respectively. There was a weak positive correlation between serum and salivary cortisol values, but this association was not statistically significant. CONCLUSION: The development of locally derived adult reference intervals can improve the diagnostic utility of serum and salivary cortisol assessment and strengthen the reliability of adrenal insufficiency diagnoses in our population.

Psychometric properties of the Russian version of the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition with observable cognitive and behavioral impairment. The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is a tool developed specifically for people with ALS (pwALS) and previously translated into Russian, but the psychometric properties have not yet been explored. The aim was to explore and determine the psychometric properties of the Russian-version of ECAS (ECAS-R). METHODS: 56 Russian speaking pwALS, 32 of their caregivers and 26 healthy controls were recruited for the study. They completed the ECAS-R, Patient Health Questionnaire-9 (PHQ-9) and Montreal Cognitive Assessment (MoCA). King Staging System was also utilized. Internal consistency, divergent and convergent validity, as well as culturally-derived cutoff scores of ECAS-R were determined. RESULTS: The internal consistency of ECAS-R was good (Cronbach's alpha = 0.73). Convergent validity was observed though a strong correlation between the ECAS-R and MoCA scores. No correlation between ECAS-R and PHQ-9 were observed in terms of divergent validity. Based on culturally-derived cutoff scores, 64.2% (N = 36) of pwALS displayed cognitive impairment, with the most affected cognitive domains as executive function and language. Apathy was the most common behavioral impairment for pwALS followed by a loss of sympathy/empathy. CONCLUSIONS: The ECAS-R is valid and reliable tool for the screening for the cognitive and behavioral impairment in Russian-speaking pwALS, with culturally-derived cutoffs presented.

Interdisciplinary Approach to Expedited Outpatient Gastrostomy Tube Placement in Head and Neck Cancer Patients: A Single Center Retrospective Study.

RATIONALE AND OBJECTIVE: Treatment for head and neck cancer (HNC) can lead to decreased oral intake which often requires gastrostomy tube (g-tube) placement to provide nutritional support. A multidisciplinary team (MDT) consisting of interventional radiology (IR), HNC oncology and surgery, nutrition, and speech language pathology departments implemented an expedited outpatient g-tube placement pathway to reduce hospital stays and associated costs, initiate feeds sooner, and improve communication between care teams. This single center study investigates differences in complications, time to procedure and costs savings with implementing this pathway. METHODS: 142 patients with HNC who underwent elective image guided g-tube placement by IR from 2015 to 2022 were identified retrospectively. 52 patients underwent the traditional pathway, and 90 patients underwent the expedited pathway. Patient demographics, procedure characteristics, periprocedural costs and 90-day complication rates were collected and compared statistically. RESULTS: The 90-day complication rate was comparable between groups (traditional=32.7%; expedited=22.2%; p-value=0.17). The expedited pathway decreased the time from consult to procedure by 11.1 days (95% CI 7.6 - 14.6; p < 0.001) and decreased charge per procedure by $2940 (95% CI $989-$4891; p < 0.001). CONCLUSION: A MDT for the treatment of patients with HNC successfully provided enteral nutrition support faster, with fewer associated costs, and in a more patient centered approach than previously done at this institution.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

Mechanisms of Post-Stroke Fatigue: A Follow-Up From the Third Stroke Recovery and Rehabilitation Roundtable.

BACKGROUND: Post-stroke fatigue (PSF) is a significant and highly prevalent symptom, whose mechanisms are poorly understood. The third Stroke Recovery and Rehabilitation Roundtable paper on PSF focussed primarily on defining and measuring PSF while mechanisms were briefly discussed. This companion paper to the main paper is aimed at elaborating possible mechanisms of PSF. METHODS: This paper reviews the available evidence that potentially explains the pathophysiology of PSF and draws parallels from fatigue literature in other conditions. We start by proposing a case for phenotyping PSF based on structural, functional, and behavioral characteristics of PSF. This is followed by discussion of a potentially significant role of early inflammation in the development of fatigue, specifically the impact of low-grade inflammation and its long-term systemic effects resulting in PSF. Of the many neurotransmitter systems in the brain, the dopaminergic systems have the most evidence for a role in PSF, along with a role in sensorimotor processing. Sensorimotor neural network dynamics are compromised as highlighted by evidence from both neurostimulation and neuromodulation studies. The double-edged sword effect of exercise on PSF provides further insight into how PSF might emerge and the importance of carefully titrating interventional paradigms. CONCLUSION: The paper concludes by synthesizing the presented evidence into a unifying model of fatigue which distinguishes between factors that pre-dispose, precipitate, and perpetuate PSF. This framework will help guide new research into the biological mechanisms of PSF which is a necessary prerequisite for developing treatments to mitigate the debilitating effects of post-stroke fatigue.

Prevalence and risk factors of diabetes foot ulcers in Kano, northwestern Nigeria.

BACKGROUND: Foot complications account for more hospital admissions than any other diabetes mellitus (DM) complications with adverse outcomes being foot ulcers and amputation. OBJECTIVE: To determine the prevalence and risk factors of diabetic foot ulcers in Kano, Northwestern Nigeria. METHODS: A descriptive cross-sectional study was conducted in the diabetes outpatient clinics and medical and surgical wards of two hospitals in Kano, Nigeria. Data were collected on socio-demographic characteristics, type, and duration of DM. The study subjects were assessed for the presence of and risk factors for foot ulcers. RESULTS: We recruited 394 patients with DM (163 males and 231 females) with a mean (SD) age and duration of DM of 50.8 ± 12.5 years and 7.72 ± 6.65 years respectively. Type 2 DM was present in 95% of the study subjects. Diabetic foot ulcer (DFU) was present in 57 (14.5%) of the patients. Risk factors associated with DFU assessed using univariate analysis were older age, longer duration of DM, presence of peripheral neuropathy (PN), peripheral arterial disease (PAD), diabetic retinopathy, nephropathy, foot deformities, previous DFU, and poor glycemic control. The independent determinants of DFU were previous DFU, foot deformities, retinopathy, PN, PAD, and poor glycemic control. CONCLUSION: DFU can be found in our setting and the predominant risk factors for DFU are common and remain unchanged in our environment. This study, therefore, buttresses the effect of early detection and treatment of DM in preventing the complications that arise from the disease.

Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria.

Background: Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)-treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). Methods: This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. Results: The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2-162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4-27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (ß = -2.83%, 95% CI, -4.44% to -1.21%, p = 0.001), estimated glomerular filtration rate (ß = -0.04%, 95% CI, -0.07% to -0.01%, p = 0.004) and LDL cholesterol (ß = -1.12%, 95% CI, -2.13% to -0.11%, p = 0.029). Conclusion: HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted.

A global survey on the attitudes of neurologists and psychiatrists about functional/psychogenic/dissociative/nonepileptic-seizures/attacks, in the search of its name.

PURPOSE: We conducted an observational study to investigate the opinions of neurologists and psychiatrists all around the world who are taking care of patients with seizures [epilepsy and functional seizures (FS)]. METHODS: Practicing neurologists and psychiatrists from around the world were invited to participate in an online survey. On 29th September 2022, an e-mail including a questionnaire was sent to the members of the International Research in Epilepsy (IR-Epil) Consortium. The study was closed on 1st March 2023. The survey, conducted in English, included questions about physicians' opinions about FS and anonymously collected data. RESULTS: In total, 1003 physicians from different regions of the world participated in the study. Both neurologists and psychiatrists identified "seizures" as their preferred term. Overall, the most preferred modifiers for "seizures" were "psychogenic" followed by "functional" by both groups. Most participants (57.9%) considered FS more difficult to treat compared to epilepsy. Both psychological and biological problems were considered as the underlying cause of FS by 61% of the respondents. Psychotherapy was considered the first treatment option for patients with FS (79.9%). CONCLUSION: Our study represents the first large-scale attempt of investigating physicians attitudes and opinions about a condition that is both frequent and clinically important. It shows that there is a broad spectrum of terms used by physicians to refer to FS. It also suggests that the biopsychosocial model has gained its status as a widely used framework to interpret and inform clinical practice on the management of patients.

Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control.

BACKGROUND: Patients with type-2 (T2) cytokine-low severe asthma often have persistent symptoms despite suppression of T2 inflammation with corticosteroids. OBJECTIVES: We sought to analyze whole blood transcriptome from 738 samples in T2-biomarker-high/-low patients with severe asthma to relate transcriptomic signatures to T2 biomarkers and asthma symptom scores. METHODS: Bulk RNA-seq data were generated for blood samples (baseline, week 24, week 48) from 301 participants recruited to a randomized clinical trial of corticosteroid optimization in severe asthma. Unsupervised clustering, differential gene expression analysis, and pathway analysis were performed. Patients were grouped by T2-biomarker status and symptoms. Associations between clinical characteristics and differentially expressed genes (DEGs) associated with biomarker and symptom levels were investigated. RESULTS: Unsupervised clustering identified 2 clusters; cluster 2 patients were blood eosinophil-low/symptom-high and more likely to be receiving oral corticosteroids (OCSs). Differential gene expression analysis of these clusters, with and without stratification for OCSs, identified 2960 and 4162 DEGs, respectively. Six hundred twenty-seven of 2960 genes remained after adjusting for OCSs by subtracting OCS signature genes. Pathway analysis identified dolichyl-diphosphooligosaccharide biosynthesis and assembly of RNA polymerase I complex as significantly enriched pathways. No stable DEGs were associated with high symptoms in T2-biomarker-low patients, but numerous associated with elevated T2 biomarkers, including 15 that were upregulated at all time points irrespective of symptom level. CONCLUSIONS: OCSs have a considerable effect on whole blood transcriptome. Differential gene expression analysis demonstrates a clear T2-biomarker transcriptomic signature, but no signature was found in association with T2-biomarker-low patients, including those with a high symptom burden.

Low Magnesium Concentration Enforces Bone Calcium Deposition Irrespective of 1,25-Dihydroxyvitamin D3 Concentration.

Efficient coordination between Mg2+ and vitamin D maintains adequate Ca2+ levels during lactation. This study explored the possible interaction between Mg2+ (0.3, 0.8, and 3 mM) and 1,25-dihydroxyvitamin D3 (1,25D; 0.05 and 5 nM) during osteogenesis using bovine mesenchymal stem cells. After 21 days, differentiated osteocytes were subjected to OsteoImage analysis, alkaline phosphatase (ALP) activity measurements, and immunocytochemistry of NT5E, ENG (endoglin), SP7 (osterix), SPP1 (osteopontin), and the BGLAP gene product osteocalcin. The mRNA expression of NT5E, THY1, ENG, SP7, BGLAP, CYP24A1, VDR, SLC41A1, SLC41A2, SLC41A3, TRPM6, TRPM7, and NIPA1 was also assessed. Reducing the Mg2+ concentration in the medium increased the accumulation of mineral hydroxyapatite and ALP activity. There was no change in the immunocytochemical localization of stem cell markers. Expression of CYP24A1 was higher in all groups receiving 5 nM 1,25D. There were tendencies for higher mRNA abundance of THY1, BGLAP, and NIPA1 in cells receiving 0.3 mM Mg2+ and 5 nM 1,25D. In conclusion, low levels of Mg2+ greatly enhanced the deposition of bone hydroxyapatite matrix. The effect of Mg2+ was not modulated by 1,25D, although the expression of certain genes (including BGLAP) tended to be increased by the combination of low Mg2+ and high 1,25D concentrations.

Functionalized bioadhesion-enhanced carboxymethyl cellulose/polyvinyl alcohol hybrid hydrogels for chronic wound dressing applications.

Wounds produced by trauma, burns, and chronic diseases cause millions of patients to suffer discomfort, pain, and, in many cases, disability and death, leading to enormous health, social and financial impacts globally. Regrettably, current clinical treatments for chronic wounds remain unsatisfactory. Thus, this study reports for the first time the design, development, and synthesis of chemically biofunctionalized hybrid hydrogels made of carboxymethyl cellulose (CMC) and poly(vinyl alcohol) (PVA) crosslinked by citric acid using an entirely biocompatible and green process. They demonstrated suitable physicochemical properties, cytocompatibility, and hemocompatibility to be applied as a smart wound dressing for skin tissue engineering. These novel hybrids were biofunctionalized with l-arginine and RGD peptide through carbodiimide mediated-amide formation to promote bioadhesion of fibroblast and keratinocyte cells as a potential enhancement for wound healing and skin tissue engineering applications.

Treatment of Hepatocellular Carcinoma by Multimodal In Situ Vaccination Using Cryoablation and a Plant Virus Immunostimulant.

PURPOSE: To test the hypothesis that cryoablation combined with intratumoral immunomodulating nanoparticles from cowpea mosaic virus (CPMV) as an in situ vaccination approach induces systemic antitumoral immunity in a murine model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Mice with bilateral, subcutaneous RIL-175 cell-derived HCCs were randomized to 4 groups: (a) phosphate-buffered saline (control), (b) cryoablation only (Cryo), (c) CPMV-treated only (CPMV), and (d) cryoablation plus CPMV-treated (Cryo + CPMV) (N = 11-14 per group). Intratumoral CPMV was administered every 3 days for 4 doses, with cryoablation performed on the third day. Contralateral tumors were monitored. Tumor growth and systemic chemokine/cytokine levels were measured. A subset of tumors and spleens were harvested for immunohistochemistry (IHC) and flow cytometry. One- or 2-way analysis of variance was performed for statistical comparisons. A P value of <.05 was used as the threshold for statistical significance. RESULTS: At 2 weeks after treatment, the Cryo and CPMV groups, alone or combined, outperformed the control group in the treated tumor; however, the Cryo + CPMV group showed the strongest reduction and lowest variance (1.6-fold ± 0.9 vs 6.3-fold ± 0.5, P < .0001). For the untreated tumor, only Cryo + CPMV significantly reduced tumor growth compared with control (9.2-fold ± 0.9 vs 17.8-fold ± 2.1, P = .01). The Cryo + CPMV group exhibited a transient increase in interleukin-10 and persistently decreased CXCL1. Flow cytometry revealed natural killer cell enrichment in the untreated tumor and increased PD-1 expression in the spleen. Tumor-infiltrating lymphocytes increased in Cryo + CPMV-treated tumors by IHC. CONCLUSIONS: Cryoablation and intratumoral CPMV, alone or combined, demonstrated potent efficacy against treated HCC tumors; however, only cryoablation combined with CPMV slowed the growth of untreated tumors, consistent with an abscopal effect.

Apathy in amyotrophic lateral sclerosis: systematic review and meta-analysis of frequency, correlates, and outcomes.

Objectives: To determine the frequency and correlates of apathy in amyotrophic lateral sclerosis (ALS) and its influence on the prognosis of the disease.Methods: Three databases were searched: MEDLINE, PubMed, and Google Scholar. Quantitative synthesis of the frequency of apathy in ALS was conducted using random effects in Stata (College Station, TX). Meta-regression and subgroup analyses were conducted to investigate the association between frequency of apathy in ALS and different covariates.Results: Fifty-two studies (51 cohorts) were included in the analysis. The pooled frequency of apathy in ALS was 25% (95% confidence interval (CI) 14-35%) according to the studies that used self-rated tools and 34% (95% CI 27-41%) according to studies that used informant-rated tools. The emergence of apathy was associated with cognitive decline and bulbar onset of the disease. There was no consistent relationship between apathy and disease stage or the severity of depression. Structural brain imaging studies established that ALS patients with apathy exhibited more prominent changes with structural and functional brain imaging particularly involving fronto-subcortical regions of the brain. Overall, apathy worsened the long-term prognosis of ALS.Discussion: Apathy affects up to a third of ALS patients аnd develops in the context of progressive neurodegeneration. Increased awareness and understanding of non-motor symptoms in ALS highlights the potential utility of apathy as an outcome measure in future clinical trial design.

"I Would Rather Take the Vaccine Than Undergo Weekly Testing": Correlates of Health Workers' Support for COVID-19 Vaccine Mandates.

This study examined the support for vaccine mandates and uptake among clinical and non-clinical staff at a tertiary hospital in northern Nigeria, focusing on variation of survey responses based on job position, socio-demographic characteristics, and perceived risk of infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Using an explanatory, sequential, mixed-methods design and deploying a pragmatic paradigm, 370 healthcare workers were administered structured questionnaires. This was followed by in-depth interviews with a sub-sample of respondents to further clarify the responses regarding support for the coronavirus disease 2019 (COVID-19) vaccine mandate. Findings demonstrated that less than one-half of respondents supported the COVID-19 mandate, and only one in three had received the recommended COVID-19 vaccine doses. Support for the vaccine mandate and vaccine uptake were predicted by profession, work experience, number of children, health status, and risk perception. Support for the vaccine mandate was ascribed to ethical and professional duty, whereas opposition was associated with respect for autonomy and human rights. This study documents the need to enhance support for vaccine mandates and uptake among healthcare workers through sustainable strategies, as Nigeria's healthcare workers are considered a source of trust and role models for the rest of society.

Physicians' beliefs about brain surgery for drug-resistant epilepsy: A global survey.

PURPOSE: To investigate the opinions of physicians about brain surgery for drug-resistant epilepsy worldwide. METHODS: Practicing neurologists, psychiatrists, and neurosurgeons from around the world were invited to participate in an online survey. The survey anonymously collected data about demographics, years in clinical practice, discipline, nation, work setting, and answers to the questions about beliefs and attitudes about brain surgery for drug-resistant epilepsy. RESULTS: In total, 1410 physicians from 20 countries and different world regions participated. The propensity to discuss brain surgery with patients, who have drug-resistant seizures, was higher among men (versus women) [Odds Ratio (OR) 1.67, 95% CI 1.20-2.31; p = 0.002]. In comparison to neurologists, psychiatrists were less likely (OR 0.28, 95% CI 0.17-0.47; p < 0.001) and neurosurgeons were more likely (OR 2.00, 95% CI 1.08-3.72; p = 0.028) to discuss about it. Survey participants working in Africa, Asia, the Middle East, and the Former Union of Soviet Socialist Republics showed a lower propensity to discuss epilepsy surgery with patients. CONCLUSION: This study showed that on an international level, there is still a knowledge gap concerning epilepsy surgery and much needs to be done to identify and overcome barriers to epilepsy surgery for patients with drug-resistant seizures worldwide.

Imaging Biomarkers and Liquid Biopsy in Assessment of Cervical Cancer.

ABSTRACT: The role of imaging has been increasing in pretherapy planning and response assessment in cervical cancer, particularly in high-resource settings that provide access to computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). In 2018, imaging was incorporated into the International Federation of Gynecology and Obstetrics staging system for cervical cancer. Magnetic resonance imaging is advantageous over CT for evaluation of the primary cervical cancer size and extent, because of superior contrast resolution. Furthermore, quantitative methods, including diffusion-weighted and dynamic contrast-enhanced MRI, show promise in improving treatment response and prognosis evaluation. Molecular imaging with fluorodeoxyglucose-PET/CT and PET/MRI can be particularly helpful in the detection of nodal disease and distant metastases. Semiautomated delineation of 3-dimensional tumor regions of interest has facilitated the development of novel PET-derived biomarkers that include metabolic volume and radiomics textural analysis features for prediction of outcomes. However, posttreatment inflammatory changes can be a confounder and lymph node evaluation is challenging, even with the use of PET/CT. Liquid biopsy has emerged as a promising tool that may be able to overcome some of the drawbacks inherent with imaging, such as limited ability to detect microscopic metastases or to distinguish between postchemoradiotherapy changes and residual tumor. Preliminary evidence suggests that liquid biopsy may be able to identify cervical cancer treatment response and resistance earlier than traditional methods. Future work should prioritize how to best synergize imaging and liquid biopsy as an integrated approach for optimal cervical cancer management.

Prolonged heart rate recovery time after 6-minute walk test is an independent risk factor for cardiac events in heart failure: a prospective cohort study

OBJECTIVES: To determine whether the time for peak exercise heart rate to return to resting heart rate after the 6-minute walk test (6MWT) can predict cardiac events in patients with heart failure (HF) within 2 years. DESIGN: Prospective cohort study. SETTING: HF outpatient facility at a tertiary teaching hospital. PARTICIPANTS: Seventy-six patients with HF, New York Heart Association functional classification II and III, and left ventricular ejection fraction <50% MAIN OUTCOME MEASURES: Patients used a heart rate monitor to measure the time for peak exercise heart rate to return to resting heart rate after the 6MWT. Data were analysed using Polar Pro-Trainer 5 software (Kempele, Finland). Patients were followed for >2 years for cardiac events (hospitalisations and death). RESULTS: Thirty-four patients had cardiac events during the 2-year follow-up period. There was a significant difference in time to return to resting heart rate between the groups with and without cardiac events {with 3.6 [standard deviation (SD) A] vs without 2.8 (SD B) minutes; mean difference C; 95% confidence interval (CI) of the difference D to E; P=0.003}. No significant differences between patients with and without cardiac events were found for mean walking distance, mean heart rate recovery at 1 minute and mean heart rate recovery at 2 minutes. The receiver operating curve discriminated between patients with and without cardiac events (área under the curve 0.71, 95% CI 0.61 to 0.81; P< 0.001). Using logistic regression analysis, prolonged time to return to resting heart rate (≥3 minutes) independently increased the risk for cardiac events 6.9-fold (95% CI 2.34 to 20.12; P< 0.001). The Kaplan­Meier curve showed more cardiac events in patients with prolonged time to return to resting heart rate (P=0.028). CONCLUSIONS: Prolonged time to return to resting heart rate (≥3 minutes) after the 6MWT was an independent predictor of cardiac events in patients with HF.

Counseling about sudden unexpected death in epilepsy (SUDEP): A global survey of neurologists' opinions.

OBJECTIVE: To investigate the opinions and attitudes of neurologists on the counseling about sudden unexpected death in epilepsy (SUDEP) worldwide. METHODS: Practicing neurologists from around the world were invited to participate in an online survey. On February 18th, 2021, we emailed an invitation including a questionnaire (using Google-forms) to the lead neurologists from 50 countries. The survey anonymously collected the demographic data of the participants and answers to the questions about their opinions and attitudes toward counseling about SUDEP. RESULTS: In total, 1123 neurologists from 27 countries participated; 41.5% of the respondents reported they discuss the risk of SUDEP with patients and their care-givers only rarely. Specific subgroups of patients who should especially be told about this condition were considered to be those with poor antiseizure medication (ASM) adherence, frequent tonic-clonic seizures, or with drug-resistant epilepsy. The propensity to tell all patients with epilepsy (PWE) about SUDEP was higher among those with epilepsy fellowship. Having an epilepsy fellowship and working in an academic setting were factors associated with a comfortable discussion about SUDEP. There were significant differences between the world regions. CONCLUSION: Neurologists often do not discuss SUDEP with patients and their care-givers. While the results of this study may not be representative of practitioners in each country, it seems that there is a severe dissociation between the clinical significance of SUDEP and the amount of attention that is devoted to this matter in daily practice by many neurologists around the world.