Categories
Nevin Manimala Statistics

Genetic and immune characteristics of sentinel lymph node metastases and multiple lymph node metastases compared to their matched primary breast tumours

EBioMedicine. 2021 Aug 25;71:103542. doi: 10.1016/j.ebiom.2021.103542. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with breast cancer presenting with single lymph node metastasis (from a sentinel node) experience prolonged survival compared to patients with multiple lymph node metastases (≥3). However, little information is available on the genetic and immunological characteristics of breast cancer metastases within the regional lymph nodes as they progress from the sentinel lymph node (SLN) downstream to multiple regional lymph nodes (MLNs).

METHODS: Genomic profiling was performed using a next-generation sequencing panel covering 520 cancer-related genes in the primary tumour and metastatic lymph nodes of 157 female patients with breast cancer. We included primary tumours, metastatic lymph nodes and adjacent clinically normal lymph nodes (20 patients from the SLN group and 28 patients from the MLNs group) in the whole transcriptome analysis.

FINDINGS: The downstream metastatic lymph nodes (P = 0.029) and the primary breast tumours (P = 0.011) had a higher frequency of PIK3CA mutations compared to the SLN metastasis. We identified a distinct group of 14 mutations from single sentinel node metastasis and a different group of 15 mutations from multiple nodal metastases. Only 4 distinct mutations (PIK3CA, CDK4, NFKBIA and CDKN1B) were conserved in metastases from both lymph node settings. The tumour mutational burden (TMB) was significantly lower in single nodal metastasis compared to the paired primary breast cancer (P = 0.0021), while the decline in TMB did not reach statistical significance in the MLNs group (P = 0.083). In the gene set enrichment analysis, we identified 4 upregulated signatures in both primary tumour and nodal metastases from the MLNs group, including 3 Epithelial-mesenchymal transition(EMT) signatures and 1 angiogenesis signature. Both the CD8/Treg ratio and the CD8/EMT ratio were significantly higher in adjacent normal lymph nodes from patients with a single metastasis in the SLN compared with samples from the MLNs group (P = 0.045 and P = 0.023, respectively). This suggests that the immune defence from the MLNs patients might have a less favourable microenvironment, thus permitting multiple lymph nodes metastasis.

INTERPRETATION: Single lymph node metastases and multiple lymph node metastases have significant differences in their molecular profiles and immune profiles. The findings are associated with more aggressive tumour characteristics and less favourable immune charactoristics in patients with multiple nodal metastases compared to those with a single metastasis in the sentinel node.

FUNDING: This work was supported by funds from High-level Hospital Construction Project (DFJH201921), the National Natural Science Foundation of China (81902828 and 82002928), the Fundamental Research Funds for the Central Universities (y2syD2192230), and the Medical Scientific Research Foundation of Guangdong Province (B2019039).

PMID:34454403 | DOI:10.1016/j.ebiom.2021.103542

Categories
Nevin Manimala Statistics

Impact of volume, immunoglobulin G concentration, and feeding method of colostrum product on neonatal nursing behavior and transfer of passive immunity in beef calves

Animal. 2021 Aug 25;15(9):100345. doi: 10.1016/j.animal.2021.100345. Online ahead of print.

ABSTRACT

One-third of beef calves fail to achieve adequate transfer of passive immunity (TPI) through timely ingestion of colostrum, which substantially increases their risk of preweaning morbidity and mortality. Two randomized clinical trials were designed to assess the impact of volume, immunoglobulin G (IgG) concentration, and feeding method of colostrum product on neonatal nursing behavior and TPI. In Trial 1, 47 calves were randomly assigned to receive one of three colostrum interventions by oro-esophageal tube feeder (OET): 1 L with 100 g/L IgG, 1.4 L with 70 g/L IgG, or 2 L with 100 g/L IgG. In Trial 2, 29 calves were randomly assigned to be fed 1 L of colostrum product with 100 g/L IgG by either nipple bottle (NB) or OET. Colostrum intervention (i.e. feeding of colostrum product) occurred within 60 minutes of birth. Cow-calf pairs were monitored by video surveillance in individual stalls for 24 h. Dam colostrum was collected at 10 minutes and calf serum was collected at 24-36 h after birth to assess IgG concentration. Differences among colostrum intervention groups on latency to stand and nurse were analyzed using Kaplan-Meier survival curves and Cox proportional hazard models. The impact of colostrum intervention group on TPI was assessed using multivariable linear regression modeling. In Trial 1, calves fed 1.4 L with 70 g/L IgG by OET nursed from their dams statistically significantly earlier compared to calves fed 1 L with 100 g/L IgG (P = 0.003) and calves fed 2 L with 100 g/L IgG (P = 0.008). Six of the 15 calves in the NB group in Trial 2 refused to consume part of the colostrum feeding offered by bottle and required follow-up tube feeding of the remaining volume. These calves were analyzed as a separate group (NB + OET). Calves fed 1 L by NB stood and nursed statistically significantly earlier than calves fed by OET (P = 0.005) or a combination of NB + OET (P = 0.003). Calf serum IgG concentrations were not statistically significantly different among colostrum intervention groups (P > 0.1). Overall, the colostrum interventions assessed in this study led to only one calf with failed TPI. While statistically significant differences in serum IgG concentrations were not detected in this study, subsequent nursing behavior did vary and was improved by feeding a moderate volume (1.4 L with 70 g/L IgG) of colostrum when using an OET, and by using the NB when feeding a smaller volume (1 L with 100 g/L IgG).

PMID:34454347 | DOI:10.1016/j.animal.2021.100345

Categories
Nevin Manimala Statistics

Expression of orexin-A (hypocretin-A) in the hypothalamus after traumatic brain injury: A postmortem evaluation

Forensic Sci Int. 2021 Aug 19;327:110961. doi: 10.1016/j.forsciint.2021.110961. Online ahead of print.

ABSTRACT

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity. The key component of TBI pathophysiology is traumatic axonal injury (TAI), commonly referred to as diffuse axonal injury (DAI). Coma is a serious complication which can occur following traumatic brain injury (TBI). Recently, studies have shown that the central orexinergic/ hypocretinergic system exhibit prominent arousal promoting actions. Therefore, the purpose of this study is to investigate by immunohistochemistry the expression of beta-amyloid precursor protein (β-APP) in white matter of parasagittal region, corpus callosum and brainstem and the expression of orexin-A (ORXA) in the hypothalamus after traumatic brain injury. RESULTS: DAI was found in 26 (53.06%) cases, assessed with β-APP immunohistochemical staining in parasagittal white matter, corpus callosum and brainstem. Orexin-A immunoreactivity in hypothalamus was completely absent in 5 (10.2%) of the cases; moderate reduction of ORXA was observed in 9 (18.4%) of the cases; and severe reduction was observed in 7 (14.3%) of the cases. A statistically significant correlation was found between β-APP immunostaining in white matter, corpus callosum and brainstem in relation to survival time (p < 0.002, p < 0.003 and p < 0.005 respectively). A statistically positive correlation was noted between ORX-A immunoreactivity in hypothalamus to survival time (p < 0.003). An inverse correlation was noted between the expression of β-APP in the regions of brain studied to the expression of ORX-A in the hypothalamus of the cases studied (p < 0.005). CONCLUSIONS: The present study demonstrated by immunohistochemistry that reduction of orexin-A neurons in the hypothalamus, involved in coma status and arousal, enhanced the immunoexpression of β-APP in parasagital white matter, corpus callosum and brainstem.

PMID:34454377 | DOI:10.1016/j.forsciint.2021.110961

Categories
Nevin Manimala Statistics

The prevalence of anxiety in general hospital inpatients: A systematic review and meta-analysis

Gen Hosp Psychiatry. 2021 Aug 14;72:131-140. doi: 10.1016/j.genhosppsych.2021.08.004. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the prevalence of anxiety in general hospital inpatients by conducting a systematic review and meta-analysis of all relevant published studies.

METHOD: We searched Ovid Medline, Ovid Embase and Ovid PsycINFO from inception to December 2020. We included studies of the prevalence of anxiety symptoms of clinically significant severity (using cut-off scores on rating scales) and of the prevalence of anxiety disorders (using diagnostic interviews) in general hospital inpatients. Two independent reviewers assessed articles and extracted data. The review is registered with PROSPERO, number CRD42020189722.

RESULTS: We included 32 studies. Pooled prevalence estimates in random-effects meta-analyses were: anxiety symptoms 28% (95% CI 19% to 38%, 95% prediction interval 5% to 72%), any anxiety disorder 8% (95% CI 5% to 12%, 95% prediction interval 2% to 33%), panic disorder 3% (95% CI 2% to 4%, 95% prediction interval 1% to 8%), generalized anxiety disorder 5% (95% CI 3% to 8%, 95% prediction interval 1% to 23%). There was high heterogeneity in prevalence, little of which was explained in exploratory analyses of a limited number of potential determinants.

CONCLUSION: Anxiety symptoms of clinically significant severity affect more than one in four inpatients and anxiety disorders affect nearly one in ten.

PMID:34454342 | DOI:10.1016/j.genhosppsych.2021.08.004

Categories
Nevin Manimala Statistics

Association of echocardiographic parameters with chest computed tomography score in patients with COVID-19 disease

Adv Med Sci. 2021 Aug 21;66(2):403-410. doi: 10.1016/j.advms.2021.08.001. Online ahead of print.

ABSTRACT

PURPOSE: Although coronavirus disease 2019 (COVID-19) primarily affects the pulmonary system, the involvement of the heart has become a well-known issue. Pulmonary CT plays an additive role in the diagnosis and prognosis of the disease. We aimed to investigate the association of echocardiographic indices with pulmonary CT scores and mortality in COVID-19 patients.

MATERIALS AND METHODS: A total of 123 patients diagnosed with COVID-19 were included in this study. The British Society of Thoracic Imaging (BSTI) score and echocardiographic parameters were calculated, and echocardiographic indices were compared between BSTI score grades.

RESULTS: During in-hospital follow-up, 36 of 123 patients (29.3%) had died. BSTI score, IVS, LVPWd, RV mid-diameter, RV basal diameter, RV longitudinal diameter, sPAP, and RVMPI were higher, and RVFAC, TAPSE, and RVS were lower in the non-survivor group than in the survivor group. There were statistically significant changes between BSTI scores in terms of LVPWd, RV mid diameter, RV basal diameter, RV longitudinal diameter, sPAP, RVFAC, RVMPI, and TAPSE. BSTI score was positively correlated with sPAP and RV basal diameter and negatively correlated with TAPSE and RVFAC. Multivariate logistic regression analysis demonstrated that sPAP (OR ​= ​1.071, p ​= ​0.002) and RV basal diameter (OR ​= ​1.184, p ​= ​0.005) were independent predictors of high BSTI scores (grade 4 and 5). Furthermore, age, sPAP, and a high BSTI score (grade 5) were independent predictors of in-hospital mortality in COVID-19 patients.

CONCLUSION: Echocardiographic indices were correlated with BSTI scores, and patients with higher BSTI scores had more cardiac involvement in COVID-19.

PMID:34454343 | DOI:10.1016/j.advms.2021.08.001

Categories
Nevin Manimala Statistics

Load applied on osseointegrated implant by transfemoral bone-anchored prostheses fitted with state-of-the-art prosthetic components

Clin Biomech (Bristol, Avon). 2021 Aug 24;89:105457. doi: 10.1016/j.clinbiomech.2021.105457. Online ahead of print.

ABSTRACT

BACKGROUND: This study presented the load profile applied on transfemoral osseointegrated implants by bone-anchored prostheses fitted with state-of-the-art ÖSSUR microprocessor-controlled Rheo Knee XC and energy-storing-and-returning Pro-Flex XC or LP feet during five standardized daily activities.

METHODS: This cross-sectional cohort study included 13 participants fitted with a press-fit transfemoral osseointegrated implant. Loading data were directly measured with the tri-axial transducer of an iPecsLab (RTC Electronics, USA) fitted between the implant and knee unit. The loading profile was characterized by spatio-temporal gaits variables, magnitude of loading boundaries as well as onset and magnitude of loading extrema during walking, ascending and descending ramp and stairs.

FINDINGS: A total of 2127 steps was analysed. The cadence ranged between 36 ± 7 and 47 ± 6 strides/min. The absolute maximum force and moments applied across all activities was 1322 N, 388 N and 133 N as well as 22 Nm, 52 Nm and 88 Nm on and around the long, anteroposterior and mediolateral axes of the implant, respectively.

INTERPRETATION: This study provided new benchmark loading data applied by transfemoral bone-anchored prostheses fitted with selected ÖSSUR state-of-the-art components. Outcomes suggested that such prostheses can generate relevant loads at the interface with the osseointegrated implant to restore ambulation effectively. This study is a worthwhile contribution toward a systematic recording, analysis, and reporting of ecological prosthetic loading profiles as well as closing the evidence gaps between prescription and biomechanical benefits of state-of-the-art components. Hopefully, this will contribute to improve outcomes for growing number of individuals with limb loss opting for bionic solutions.

PMID:34454327 | DOI:10.1016/j.clinbiomech.2021.105457

Categories
Nevin Manimala Statistics

A most painful knee does not induce interlimb differences in knee and hip moments during gait in patients with knee osteoarthritis

Clin Biomech (Bristol, Avon). 2021 Aug 20;89:105455. doi: 10.1016/j.clinbiomech.2021.105455. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with knee osteoarthritis can adapt their gait to unload the most painful knee joint in order to try to reduce pain and improve physical function. However, these gait adaptations can cause higher loads on the contralateral joints. The aim of the study was to investigate the interlimb differences in knee and hip frontal plane moments during gait in patients with knee osteoarthritis and in healthy controls.

METHODS: Forty patients with knee osteoarthritis and 19 healthy matched controls were measured during comfortable treadmill walking. Frontal plane joint moments were obtained of both hip and knee joints. Differences in interlimb moments within each group were assessed using statistical parametric mapping and discrete gait parameters.

FINDINGS: No interlimb differences were observed in patients with knee osteoarthritis and control subjects at group level. Furthermore, the patients presented similar interlimb variability as the controls. In a small subgroup (n = 12) of patients, the moments in the most painful knee were lower than in the contralateral knee, while the other patients (n = 28) showed higher moments in the most painful knee compared to the contralateral knee. However, no interlimb differences in the hip moments were observed within the subgroups.

INTERPRETATION: Patients with knee osteoarthritis do not have interlimb differences in knee and hip joint moments. Patients and healthy subjects demonstrate a similar interlimb variability in the moments of the lower extremities. In this context, differences in knee pain in patients with knee osteoarthritis did not induce any interlimb differences in the frontal plane knee and hip moments.

PMID:34454328 | DOI:10.1016/j.clinbiomech.2021.105455

Categories
Nevin Manimala Statistics

Endovascular and thrombolytic treatment eligibility in childhood arterial ischemic stroke

Eur J Paediatr Neurol. 2021 Aug 24;34:99-104. doi: 10.1016/j.ejpn.2021.08.004. Online ahead of print.

ABSTRACT

AIM: To describe factors affecting eligibility for, and rates of utilization of, hyperacute therapy in children with acute ischemic stroke (AIS) following establishment of our institutional acute stroke treatment pathway in 2005.

METHODS: A retrospective analysis of a prospectively enrolled, single-center cohort was performed including children age 2 – <18 years with acute AIS from 2005 through 2017. Descriptive statistics were used to summarize clinical characteristics, presentation data, and Pediatric NIH Stroke Scale (PedNIHSS) scores that were abstracted from medical records. Assessment for eligibility and administration of hyperacute therapy was determined at the time of presentation according to the institutional stroke pathway.

RESULTS: Of 90 children (median age at presentation 11.3 years, 36% female) with acute AIS, 5 (6%) received hyperacute therapy: 3 received intravenous tissue plasminogen activator (IV-tPA) alone, 1 received endovascular therapy (EVT) alone, and 1 received IV-tPA and EVT. Of 54 children (60%) who presented within 4.5 h of time last seen well, 6 had PedNIHSS scores 6-24, no medical contraindication to IV-tPA, and a partial or complete vessel occlusion. Of 7 children >3 years old who presented after EVT became available at our hospital and within 6 h of time last seen well with a PedNIHSS score 6-24, 3 (43%) had a large vessel occlusion (LVO). Two patients underwent EVT and the other patient was not transferred until >6 h from time last seen well.

CONCLUSIONS: Delay to presentation and diagnosis of childhood acute AIS, mild neurologic deficits at presentation, medical contraindications to IV-tPA, and lack of vessel occlusion on acute neuroimaging contribute to low rates of hyperacute treatment in children with acute AIS.

PMID:34454335 | DOI:10.1016/j.ejpn.2021.08.004

Categories
Nevin Manimala Statistics

Air monitoring with passive samplers for dioxin-like persistent organic pollutants in developing countries (2017-2019)

Chemosphere. 2021 Aug 19;287(Pt 1):131931. doi: 10.1016/j.chemosphere.2021.131931. Online ahead of print.

ABSTRACT

As part of the global monitoring plan on persistent organic pollutants (GMP) under the Stockholm Convention passive air samplers equipped with polyurethane foam disks (PUFs) were applied to monitor dioxin-like POPs. For sampling, toluene-pretreated PUFs were exposed for three months during two years. Chemical analysis was performed in one accredited expert laboratory using internationally accepted methods; for comparison, all results were normalized to one PUF and 3 month exposure. Total TEQs, using WHO2005-TEFs, were lowest in the Pacific Islands countries (PAC) and had similar mean values in Africa (16.8 pg TEQ/PUF), Asia (16.9 pg TEQ/PUF), and Latin American and Caribbean countries (GRULAC, 13.3 pg TEQ/PUF). Using median values, Asia (13.4 pg TEQ/PUF) and GRULAC (13.1 pg TEQ/PUF) had higher amounts than Africa (6.1 pg TEQ/PUF) and PAC (2.1 pg TEQ/PUF). The contribution of PCDD/PCDF to the total TEQ was 2-3-times higher than from the dl-PCB. Mono-ortho PCB did not play a role in any of the samples. The previous 40 samples during 2010/2011 and the present 195 samples from 2017/2018 did not show a statistical difference (p value = 0.3), only for GRULAC, a downward trend was identified. It is recommended combining 4 PUFs to ‘annual’ samples.

PMID:34454223 | DOI:10.1016/j.chemosphere.2021.131931

Categories
Nevin Manimala Statistics

Prognostic value of EMG genioglossus involvement in amyotrophic lateral sclerosis

Clin Neurophysiol. 2021 Jul 24;132(10):2416-2421. doi: 10.1016/j.clinph.2021.07.011. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the prognostic value of needle electromyography (EMG) genioglossus involvement in patients with amyotrophic lateral sclerosis (ALS) at diagnosis.

METHODS: We separately explored the prognostic value of clinical bulbar lower motor neuron (LMN) signs and EMG genioglossus involvement using Cox proportional hazard models adjusted for age, gender, diagnostic delay, presence of bulbar upper motor neuron (UMN) signs, EMG cervical and lumbosacral region involvement, ALSFRS-R score and C9Orf72 gene status. Then, we compared the prognostic value of EMG masseter and genioglossus abnormalities in a subset of patients in whom both muscles were analysed.

RESULTS: 103 ALS patients were included in the study. Neurophysiological genioglossus involvement was associated with a shorter survival (p = 0.002), a shorter time to moderate dysphagia (p = 0.0001) and to severe dysarthria (p = 0.012). Its prognostic value was still evident in patients without clinical bulbar LMN signs. Bulbar clinical LMN signs were only associated with an earlier onset of moderate dysphagia (p = 0.0001). EMG masseter abnormalities did not reach statistical significance with regard to all the clinical milestones.

CONCLUSIONS: Genioglossus EMG at diagnosis could provide important information about ALS progression rate. The masseter muscle seems to be less involved in ALS.

SIGNIFICANCE: EMG genioglossus involvement is a prognostic factor in ALS.

PMID:34454268 | DOI:10.1016/j.clinph.2021.07.011