Plasma C-reactive Protein Levels Research Articles

The Association of Prenatal C-Reactive Protein Levels With Childhood Asthma and Atopy

The pathogenesis of childhood asthma is complex, and determinants of risk may begin in utero. To describe the association of systemic prenatal inflammation, measured by plasma C-reactive protein (CRP), with childhood asthma, eczema, and allergic rhinitis. A total of 522 maternal-offspring pairs from the Vitamin D Antenatal Asthma Reduction Trial were included. Prenatal plasma CRP level was measured between 10 and 18 weeks of gestation and between 32 and 38 weeks of gestation. Offspring asthma, eczema, and allergic rhinitis were assessed quarterly between birth and age 6 years. We performed mediation analyses of prenatal CRP on the association between several maternal characteristics and offspring asthma. Elevated early and late prenatal CRP and an increase in CRP from early to late pregnancy were associated with asthma by age 6 years (early: adjusted odds ratio [aOR], 1.76, 95% CI, 1.12-2.82, P= .02; late: aOR, 2.45, 95% CI, 1.47-4.18, P < .001; CRP increase: aOR, 2.06, 95% CI, 1.26-3.39, P < .004). Prenatal CRP and childhood asthma associations were strengthened among offspring with atopic asthma (early: aOR, 3.78, 95% CI, 1.49-10.64, P= .008; late: aOR, 4.84, 95% CI, 1.68-15.50, P= .005; CRP increase: aOR, 3.01, 95% CI, 1.06-9.16, P=.04). Early and late prenatal CRP mediated 96% and 86% of the association between maternal prepregnancy body mass index and offspring asthma, respectively. Higher prenatal CRP and an increase in CRP from early to late pregnancy are associated with childhood asthma. Systemic inflammation during pregnancy associated with modifiable maternal characteristics may be an important determinant of childhood asthma risk.

Inflammatory markers at baseline correlate with subsequent clinical response to quetiapine in patients with bipolar disorder.

Recent studies proposed the existence of a correlation between patients' inflammatory status and therapy response in bipolar disorder (BD). Here we investigated the correlation between levels of inflammatory markers and quetiapine (QUE) effects in BD patients. In 15 hospitalised BD patients, we investigated changes in inflammatory markers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR) and cytokines after a 6-week treatment with QUE monotherapy. We found QUE treatment to significantly reduce CRP and IL-6 plasma levels. Moreover, we found higher CRP and IL-6 plasma levels at baseline correlated with better improvement of patients' clinical symptoms. The reported results, although preliminary, could be useful in clinical practice, providing not only markers for QUE response, but also allowing for identification of new targets and new therapies for the treatment of this condition.

C-reactive Protein as a Predictor of Severity in Chronic Obstructive Pulmonary Disease: An Experience From a Tertiary Care Hospital.

BackgroundIn this study, we aimed to determine the frequency of raised C-reactive protein (CRP) levels and their association with the severity of the disease.MethodologyThis descriptive cross-sectional study was conducted at the Shifa International Hospital, Islamabad, from June 2018 to December 2018 in the Department of Medicine. Patients attending the respiratory outpatient clinic in the Department of Medicine, Shifa International Hospital, Islamabad, with chronic obstructive pulmonary disease, meeting the sample selection criteria, were included in our study. A total of 104 patients were enrolled. All patients had plasma CRP levels measured, and forced expiratory volume in one second to forced vital capacity ratio was calculated to quantify the severity of the disease. We used SPSS version 26.0 (IBM Corp., Armonk, NY, USA) for data analysis.ResultsAll patients with levels of hs-CRP greater than 3 mg/L had stage 3 or 4 chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria, which accounted for 16.4% of the sample, while 81.7% of all patients suffering from COPD had levels greater than 1 mg/L. Only a small minority of patients, 1.9%, had normal high-sensitivity (hs)-CRP levels. The relationship between high levels of hs-CRP levels and advanced stages of COPD was statistically significant (p < 0.001).ConclusionsThe severity of COPD is directly related to the raised CRP levels, which can help in identifying these patients and managing them subsequently. It can be a useful indicator and a basis for high suspicion index and close follow-up for patients with high levels.

Neutrophil-to-lymphocyte ratio is a predictive marker for anti-MDA5 positive dermatomyositis

BackgroundNLR is a systemic inflammatory marker that have been associated with overall survival in patients with some rapidly progressive disease. There are few data about the diagnostic and predictive value of NLR in autoimmune diseases, and it has not been described in anti-MDA5 positive DM. We try to correlate neutrophil-to-lymphocyte ratio (NLR) with fatality from dermatomyositis in anti-MDA5 positive patients.MethodA retrospective study in which 195 patients were enrolled was conducted. Clinical and laboratory information was collated and ratios of neutrophil to lymphocyte counts (NLR) calculated. The primary end point was all-cause death.ResultOf the 195 patients studied, all had interstitial lung disease, including 140 survivors and 55 non-survivors. An optimal NLR cut-off value of 4.86 for mortality prediction was identified. The NLR of non-survivors was significantly higher than that of survivors (p < 0.001). Plasma levels of lactate dehydrogenase (LDH) and C-reactive protein were significantly increased when NLR was greater than 4.86. Results of multivariate analysis established that NLR > 4.86 was an independent predictor of mortality (HR: 2.52; 95%CI: 1.33–4.78; p = 0.005). Abstinence from smoking (HR: 2.66; 95%CI: 1.33–4.78; p = 0.003), emergence of rapidly progressive interstitial lung disease (RPILD; HR: 4.38; 95%CI: 2.37–8.08; p < 0.001), low plasma LDH (HR: 3.82; 95%CI: 2.06–7.11; p < 0.001) and presentation with dyspnea (HR: 2.17; 95%CI: 1.22–3.86; p = 0.009) were all protective factors predictive of survival.ConclusionNLR is a cost-effective and widely accessible biomarker with utility for risk stratification in patients with anti-MDA5 + dermatomyositis.

Oral active matrix metalloproteinase-8 immunotest may be less accurate in haemato-oncologic patients.

This study examines the associations of active matrix metalloproteinase-8 (aMMP-8) point-of-care immunotest (Periosafe) outcomes with oral health of patients with haemato-oncologic diseases. Adult patients diagnosed with haematological diseases aimed to be treated with haematopoietic stem cell transplantation (HSCT) between 2018 and 2019 were included in the study. Clinical and radiological dental examination were taken immediately prior to transplantation. The presence of oral foci of infections, caries or periodontitis was examined and compared with the outcomes of aMMP-8 immunotest. Acute oral infection foci were present in 11.9%, chronic in 44.1% and periodontitis in 42.0% of the 143 subjects. aMMP-8 immunotest was positive in 13.3% of all the 143 subjects. Among subjects with periodontitis (n=60), the aMMP-8 immunotest was also positive in 13.3% of these subjects. However, the subjects with positive aMMP-8 immunotest (n=19) had more often acute or chronic infection foci and more than one of the examined dental treatment needs compared with subjects with negative immunotest (all p < 0.05). There were no differences in age, sex, hyposalivation, DMFT-index values nor with plasma levels of leukocytes, neutrophils or C-reactive protein between subjects with positive or negative aMMP-8 immunotest. aMMP-8 immunotest accuracy might be reduced, in relation to periodontitis, in haemato-oncologic patients.

QEEG indices are associated with inflammatory and metabolic risk factors in Parkinson's disease dementia: An observational study.

SummaryBackgroundQuantitative electroencephalography (QEEG) is a reliable and non-invasive diagnostic tool to quantify cortical synaptic injury or loss in the clinical assessment of neurodegenerative diseases, and may be able to differentiate various types of dementia. We investigated if QEEG indices can differentiate Parkinson's Disease (PD) with nondementia (PD-ND) from PD with dementia (PDD), and to determine if QEEG indices correlate with inflammation and lipid metabolism markers in PD.MethodsThis clinical study collected data between July 1, 2018 and July 1, 2021 in Zhujiang Hospital of Southern Medical University in China and data was analysed. A total of 125 individuals comprising of 31 PDD, 47 patients with PD-ND and 47 healthy controls were included. We calculated the absolute spectral power (ASP) of frequency bands and the slow-to-fast frequency ratios of specific brain regions. Plasma levels of hypersensitive C-reactive protein (Hs-CRP), superoxide dismutase (SOD), and high-density lipoprotein cholesterol (HDL-C) were measured and correlations with QEEG indices were examined.FindingsA significantly higher ASP of delta frequency especially in the frontal region was observed in patients with PDD compared to PD-ND (P=0.004) and controls (P=0.000). Decreased HDL-C (OR=0.186, P=0.030), and increased Hs-CRP (OR =2.856, P=0.015) were associated with PDD. Frontal-delta ASP was negatively correlated with plasma HDL-C (r=−0.353, P=0.000) and SOD (r=−0.322, P=0.001), and positively correlated with Hs-CRP (r=0.342, P=0.000).InterpretationWe highlight novel correlations between QEEG indices and inflammation and lipid metabolism markers in PD-ND and PDD. QEEG indices, HDL-C and Hs-CRP are potentially useful for the evaluation of PDD. Our current findings suggest that peripheral inflammation might contribute to the pathogenesis of cognitive impairment and EEG slowing in PDD. The mechanism underlying frontal-delta ASP and its correlation with neuro-inflammatory and metabolic markers in PDD should be further investigated.FundingThe National Natural Science Foundation of China (NO: 81873777, 82071414); the Scientific Research Foundation of Guangzhou (NO: 202206010005); the Science and Technology Program of Guangdong of China (NO: 2020A0505100037); the High-level Hospital Construction Research Project of Maoming People's Hospital (NO: xz2020009); the Science and Technology Program of Maoming City (NO: 2021S0026). Dr EK Tan is supported by the National Medical Research Council, Singapore.

The radiographic assessment of lung edema score of lung edema severity correlates with inflammatory parameters in patients with coronavirus disease 2019-Potential new admission biomarkers to predict coronavirus disease 2019 worsening.

BackgroundCoronavirus disease 2019 (COVID-19) has placed enormous pressure on intensive care units (ICUs) and on healthcare systems in general. A deeper understanding of the pathophysiology of the most severe forms of COVID-19 would help guide the development of more effective interventions. Herein, we characterized the inflammatory state of patients with COVID-19 of varying degrees of severity to identify admission biomarkers for predicting COVID-19 worsening.DesignAdmission blood samples were obtained from 78 patients with COVID-19. Radiographic assessment of lung edema (RALE) scoring was calculated by imaging. Platelet and leukocyte counts were measured by flow cytometry, and plasma levels of C-reactive protein were assessed by immunoturbidimetry, and interleukin (IL)-8/CXCL8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monocyte chemoattractant protein-1 (MCP-1/CCL2) levels by enzyme-linked immunosorbent assay (ELISA).ResultsThe RALE score correlated with several admission hemogram (platelets, neutrophils, and lymphocytes) and inflammatory (IL-8/CXCL8, MCP-1/CCL2, IL-10, and C-reactive protein) parameters. COVID-19 worsening, based on the need for oxygen (Δoxygen supply) during hospitalization, correlated negatively with admission lymphocyte counts but positively with neutrophil-to-lymphocyte ratio and with plasma levels of the inflammatory parameters correlating with RALE score.ConclusionOur data indicate a correlation between the RALE score and Δoxygen supply and admission inflammatory status. The identification of a panel of biomarkers that reflect COVID severity might be useful to predict disease worsening during hospitalization and to guide clinical management of COVID-19-related complications. Finally, therapies targeting IL-8/CXCL8- or IL-10 activity may offer therapeutic approaches in COVID-19 treatment.

MARKERS OF LOW-GRADE INFLAMMATION IN PATIENTS WITH ACUTE CORONARY SYNDROME AND 2 TYPE DIABETES MELLITUS

Cardiovascular diseases cause approximately one-third of all deaths in the world, of which 7.5 million deaths are estimated to be due to ischemic heart disease (IHD). Acute coronary syndromes (ACS) and sudden death cause most IHD-related deaths, which represent 1.8 million deaths per year. Established, that patients with diabetes mellitus (DM) are more likely to experience of ACS and heart failure and are at greater risk for dying after an acute cardiac event, than patients without diabetes. &#x0D; The purpose of this study is evaluation of leukocyte and its populations count, leukocytes indices and plasma level of high sensitive C-reactive protein (hsCPR) in patients hospitalized due to ACS with or without of 2 type DM. &#x0D; Material and Methods. We observed of 124 patients with ACS which were randomized into two groups: 1st group – 93 patients with ACS and DM; 2nd group – 31 patients with ACS without 2 type DM. 30 apparently healthy persons were included into control group. We studied of leukocytes count and their subpopulations in blood; calculated of their subpopulation indices: neutrophils to lymphocytes ratio (NLR), neutrophils to monocytes ratio (NMR), neutrophils to lymphocytes+monocytes ratio (N/LMR), lymphocytes to monocytes ratio (NMR) at admission. The plasma levels of hs-CRP were detected by ELISA method. &#x0D; Results of study. The significant increase of white blood cells count and neutrophils count in patients with ACS at admission was detected in our study, especially in cases with DM. On the contrary, the counts of lymphocytes were decreased in patients with ACS and ACS with 2 type DM, versus data in control group. In patient with ACS the increased parameter of NMR was observed (p&lt;0.001). Similarly, the following indices were higher, compared with control group parameters: NLR – for 3.32 times (in patients with ACS and DM) and for 2.43 times (in patients with ACS and without DM) (p&lt;0.001); N/LMR – for 2.98 times (in patients with ACS and DM) and for 2.14 times (in patients with ACS and without DM) (p&lt;0.001). On the contrary, LMR was decreased in both groups of patients with ACS – for 1.4 times and 1.36 times, respectively (p&lt;0.05). The increased plasma levels of hs-CRP were detected in patients with ACS, more significant – in case of 2 type DM (fig. 1): for 2.1 times and for 2.59 times, respectively (p&lt;0.001). &#x0D; Conclusion. ACS is characterized of raised white blood cells and neutrophils count and low lymphocyte count, especially in cases of association with 2 type Diabetes Mellitus. Low-grade inflammation in patients with ACS and DM caused of increased levels of hs-CRP and some leukocyte ratios: NMR, N/LMR, NLR.

High Plasma Levels of Fortilin in Patients with Coronary Artery Disease.

Excessive apoptosis is known to be a common feature of atherosclerotic lesions. Fortilin is recognized to have potent antiapoptotic properties. An increased fortilin expression was demonstrated in atherosclerotic lesions, and fortilin knockout mice developed less atherosclerosis. However, no study has reported blood fortilin levels in patients with coronary artery disease (CAD). We investigated plasma fortilin levels in 384 patients undergoing coronary angiography. CAD severity was evaluated as the numbers of stenotic vessels and segments. CAD was found in 208 patients (one-vessel (1VD), n = 86; two-vessel (2VD), n = 68; and three-vessel disease (3VD), n = 53). Plasma C-reactive protein (CRP) levels were higher in patients with CAD than without CAD (median 0.60 vs. 0.45 mg/L, p < 0.01). Notably, fortilin levels were higher in patients with CAD than without CAD (75.1 vs. 69.7 pg/mL, p < 0.02). A stepwise increase in fortilin was found according to the number of stenotic vessels: 69.7 in CAD(−), 71.1 in 1VD, 75.7 in 2VD, and 84.7 pg/mL in 3VD (p < 0.01). Fortilin levels also correlated with the number of stenotic segments (r = 0.16) and CRP levels (r = 0.24) (p < 0.01). In a multivariate analysis, fortilin levels were independently associated with 3VD. The odds ratio for 3VD was 1.93 (95%CI = 1.01–3.71) for a high fortilin level (>70.0 pg/mL). Thus, plasma fortilin levels in patients with CAD, especially those with 3VD, were found to be high and to be associated with the severity of CAD.

A time-course comparative clinical and immune response evaluation study between the human pathogenic Orientia tsutsugamushi strains: Karp and Gilliam in a rhesus macaque (Macaca mulatta) model.

BackgroundScrub typhus is a vector-borne febrile illness caused by Orientia tsutsugamushi transmitted by the bite of Trombiculid mites. O. tsutsugamushi has a high genetic diversity and is increasingly recognized to have a wider global distribution than previously assumed.Methodology/principle findingsWe evaluated the clinical outcomes and host immune responses of the two most relevant human pathogenic strains of O. tsutsugamushi; Karp (n = 4) and Gilliam (n = 4) in a time-course study over 80 days post infection (dpi) in a standardized scrub typhus non-human primate rhesus macaque model. We observed distinct features in clinical progression and immune response between the two strains; Gilliam-infected macaques developed more pronounced systemic infection characterized by an earlier onset of bacteremia, lymph node enlargement, eschar lesions and higher inflammatory markers during the acute phase of infection, when compared to the Karp strain. C-reactive protein (CRP) plasma levels, interferon gamma (IFN-γ, interleukin-1 receptor antagonist (IL-1ra), IL-15 serum concentrations, CRP/IL10- and IFN-γ/IL-10 ratios correlated positively with bacterial load in blood, implying activation of the innate immune response and preferential development of a T helper-type 1 immune response. The O. tsutsugamushi-specific immune memory responses in cells isolated from skin and lymph nodes at 80 dpi were more markedly elevated in the Gilliam-infected macaques than in the Karp-infected group. The comparative cytokine response dynamics of both strains revealed significant up-regulation of IFN-γ, tumor necrosis factor (TNF), IL-15, IL-6, IL-18, regulatory IL-1ra, IL-10, IL-8 and granulocyte-colony-stimulating factor (G-CSF). These data suggest that the clinical outcomes and host immune responses to scrub typhus could be associated with counter balancing effects of pro- and anti-inflammatory cytokine-mediated responses.Currently, no data on characterized time-course comparisons of O. tsutsugamushi strains regarding measures of disease severity and immune response is available. Our study provides evidence for the strain-specificity of host responses in scrub typhus, which supports our understanding of processes at the initial inoculation site (eschar), systemic disease progression, protective and/or pathogenic host immune mechanisms and cellular immune memory function.Conclusions/significanceThis study characterised an improved intradermal rhesus macaque challenge model for scrub typhus, whereby the Gilliam strain infection associated with higher disease severity in the rhesus macaque model than the previous Karp strain infection. Difficulties associated with inoculum quantitation for obligate-intracellular bacteria were overcome by using functional inoculum titrations in outbred mice. The Gilliam-based rhesus macaque model provides improved endpoint measurements and contributes towards the identification of correlates of protection for future vaccine development.

Increased LRG1 Levels in Overweight and Obese Adolescents and Its Association with Obesity Markers, Including Leptin, Chemerin, and High Sensitivity C-Reactive Protein.

Leucine-rich α-2 glycoprotein1 (LRG1) is a member of the leucine-rich repeat (LRR) family that is implicated in multiple diseases, including cancer, aging, and heart failure, as well as diabetes and obesity. LRG1 plays a key role in diet-induced hepatosteatosis and insulin resistance by mediating the crosstalk between adipocytes and hepatocytes. LRG1 also promotes hepatosteatosis by upregulating de novo lipogenesis in the liver and suppressing fatty acid β-oxidation. In this study, we investigated the association of LRG1 with obesity markers, including leptin and other adipokines in adolescents (11–14 years; n = 425). BMI-for-age classification based on WHO growth charts was used to define obesity. Plasma LRG1 was measured by ELISA, while other markers were measured by multiplexing assay. Median (IQR) of LRG1 levels was higher in obese (30 (25, 38) µg/mL) and overweight (30 (24, 39) µg/mL) adolescents, compared to normal-weight participants (27 (22, 35) µg/mL). The highest tertile of LRG1 had an OR [95% CI] of 2.55 [1.44, 4.53] for obesity. LRG1 was positively correlated to plasma levels of high sensitivity c-reactive protein (HsCRP) (ρ = 0.2), leptin (ρ = 0.2), and chemerin (ρ = 0.24) with p < 0.001. Additionally, it was positively associated with plasma level of IL6 (ρ = 0.17) and IL10 (ρ = 0.14) but not TNF-α. In conclusion, LRG1 levels are increased in obese adolescents and are associated with increased levels of adipogenic markers. These results suggest the usefulness of LRG1 as an early biomarker for obesity and its related pathologies in adolescents.

Diagnosis and prognosis of acute respiratory distress syndrome related to diffuse pneumonic-type adenocarcinoma: a single-center case series study.

BackgroundThe absence of diagnosis of acute respiratory distress syndrome (ARDS) concerns 20% of cancer patients and is associated with poorer outcomes. Diffuse pneumonic-type adenocarcinoma (P-ADC) is part of these difficult-to-diagnose ARDS, but only limited data are available regarding critically ill patients with diffuse P-ADC. We sought to describe the diagnosis process and the prognosis of P-ADC related ARDS patients admitted to the intensive care unit (ICU).MethodsSingle-center observational case series study. All consecutive patients admitted to the ICU over a two-decade period presenting with (I) histologically or cytologically proven adenocarcinoma of the lung and (II) ARDS according to Berlin definition were included. Clinical, biological, radiological and cytological features of P-ADC were collected to identify diagnostic clues. Multivariate logistic regression analyses were performed to assess factors associated with ICU and hospital mortality.ResultsAmong the 24 patients included [70 (61–75) years old, 17 (71%) males], the cancer diagnosis was performed during the ICU stay in 19 (79%), and 17 (71%) required mechanical ventilation. The time between the first symptoms and the diagnosis of P-ADC was 210 days (92–246 days). A non-resolving pneumonia after 2 (2 to 3) antibiotics lines observed in 23 (96%) patients with a 34 mg/L (19 to 75 mg/L) plasma C-reactive protein level at ICU admission. Progressive dyspnea, bronchorrhea, salty expectoration, fissural bulging and compressed bronchi and vessels were present in 100%, 83%, 69%, 57% and 43% of cases. Cytological examination of sputum or broncho-alveolar lavage provided a 75% diagnostic yield. The ICU and hospital mortality rates were 25% and 63%, respectively. The time (in days) between first symptoms and diagnosis [odds ratio (OR) 1.02, 95% confidence interval (95% CI): 1.00–1.03, P=0.046] and the Simplified Acute Physiology Score II (OR 1.16, 95% CI: 1.01–1.33, P=0.040) were independently associated with ICU mortality.ConclusionsNon-resolving pneumonia after several antibiotics lines without inflammatory syndrome, associated with progressive dyspnea, salty bronchorrhea, and lobar swelling (i.e., fissural bulging, compressed bronchi and vessels) were suggestive of P-ADC. Delayed diagnosis of diffuse P-ADC seemed an independent prognostic predictor and disease timely recognition may contribute to prognosis improvement.

Longitudinal changes in inflammatory biomarkers among patients with COVID-19: A nationwide study in Iceland.

ObjectivesAll SARS‐CoV‐2‐positive persons in Iceland were prospectively monitored and those who required outpatient evaluation or were admitted to hospital underwent protocolized evaluation that included a standardized panel of biomarkers. The aim was to describe longitudinal changes in inflammatory biomarkers throughout the infection period of patients with COVID‐19 requiring different levels of care.DesignRegistry‐based study.SettingNationwide study in Iceland.PatientsAll individuals who tested positive for SARS‐CoV‐2 by real‐time polymerase chain reaction (RT‐PCR) from February 28 to December 31, 2020 in Iceland and had undergone blood tests between 5 days before and 21 days following onset of symptoms.Measurements and Main ResultsData were collected from the electronic medical record system of Landspitali–The National University Hospital of Iceland. Data analyses were descriptive and the evolution of biomarkers was visualized using locally weighted scatterplot smoothing curves stratified by the worst clinical outcome experienced by the patient: outpatient evaluation only, hospitalization, and either intensive care unit (ICU) admission or death. Of 571 included patients, 310 (54.3%) only required outpatient evaluation or treatment, 202 (35.4%) were hospitalized, and 59 (10.3%) were either admitted to the ICU or died. An early and persistent separation of the mean lymphocyte count and plasma C‐reactive protein (CRP) and ferritin levels was observed between the three outcome groups, which occurred prior to hospitalization for those who later were admitted to ICU or died. Lower lymphocyte count, and higher CRP and ferritin levels correlated with worse clinical outcomes. Patients who were either admitted to the ICU or died had sustained higher white blood cell and neutrophil counts, and elevated plasma levels of procalcitonin and D‐dimer compared with the other groups.ConclusionsLymphocyte count and plasma CRP and ferritin levels might be suitable parameters to assess disease severity early during COVID‐19 and may serve as predictors of worse outcome.

A susceptibility putative haplotype within NLRP3 inflammasome gene influences ischaemic stroke risk in the population of Punjab, India.

Despite strong genetic implications of NLRP3 inflammasome, its examination as genetic determinant of ischaemic stroke (IS) remains to be done in Punjab, which has been investigated in this study. In this case control study, 400 subjects (200 IS patients, 200 stroke free controls) were included. Contributions of 5 single nucleotide polymorphisms (SNPs) including a functional SNP within NLRP3 gene (rs10754558, rs4612666, rs2027432, rs3738488 and rs1539019) for the risk of IS were investigated through genetic models after correcting the effect of significant variables. Plasma levels of three pro‐inflammatory markers, that is, C‐reactive protein (CRP), interleukin‐1beta (IL‐1β) and interleukin‐18 (IL‐18) were measured by enzyme‐linked immunosorbent assays (ELISA). Minor alleles of 3 out of 5 SNPs (rs10754558, rs4612666 and rs1539019) exhibited association with IS risk in additive, recessive and multiplicative models. Multivariable regression analysis confirmed that higher levels of systolic blood pressure (β ± SE: 1.42 ± 0.57, p = .013), CRP (β ± SE: 1.22 ± 0.41, p = .003), IL‐1β (β ± SE: 1.78 ± 0.88, p = .043) and IL‐18 (β ± SE: 1.13 ± 0.49, p = .021) were independent risk predictors for IS. Haplotype analysis revealed a susceptibility putative haplotype GTGTA, which approximately doubled the IS risk (OR: 1.98, 95% CI: 1.12–3.78, p = .04) in dominant mode after adjusting the effect with confounding variables. This susceptibility putative haplotype GTGTA was significantly associated with increased concentrations of CRP (β = 1.21, p = .014) and IL‐1β (β = 1.53, p = .034) in dose‐dependent manner (less in carriers of 1 copy than those who had 2 copies of GTGTA).The present study has revealed a susceptibility putative haplotype GTGTA within NLRP3 gene, carriers of which have double the risk of IS by having increased plasma levels of CRP and IL‐1β in a dose‐dependent manner.

The pyrethroid insecticide permethrin confers hepatotoxicity through DNA damage and mitochondria-associated apoptosis induction in rat: Palliative benefits of Fumariaofficinalis.

Permethrin (PER) is a pyrethroid pesticide that is extensively used as an insecticide in world because of its high activity and its low mammalian toxicity. The current study was conducted to investigate the protective action of Fumaria officinalis against PER-induced liver injury in male rats. However, HPLC-DAD showed the richness of 6 components in F. officinalis (F) including quercetin, ferulic acid, and naringenin which were the most abundant. Total polyphenols, total flavonoids, and condensed tannins were studied by phytochemical screening. In vitro, antioxidant properties showed that F. officinalis exhibited the highest DPPH radical, FRAP, and H2 O2 tests and total antioxidant capacity. Wistar rats were divided into four groups: negative control group (C), positive control group (F) (200 mg F. officinalis/kg BW), PER group (34.05 mg permethrin/kg BW), and PER + F group (34.05 mg permethrin/kg BW and 200 mgF. officinalis/kg BW). Oral administration of PER led to promote a decrease of body weight and Ca2+ -ATPases and Mg2+ -ATPases activities and an increase of plasma C-reactive proteinlevel, transaminases, and hepatic ϒ-GT activities as well as hepatic and mitochondrial oxidative stress. An increase in plasma lactate-to pyruvate ratio and a reduction in complexes enzymes I, III, and IV activities were also observed. In addition, histoarchitecture of liver in PER-treatedrats showed apoptosis and necrosis as confirmed by DNA fragmentation. F. officinalis significantly exerted hepatoprotective effect by modulating hepatic alteration and mitochondrial dysfunction as well as genotoxicity. This effect could be attributed to phenolics compounds such as polyphenols, condensed tannins, and flavonoids.

Effect of Enhanced Recovery after Surgery with Integrated Traditional Chinese and Western Medicine on Postoperative Stress Response of Patients with Gastrointestinal Tumors.

Objective To investigate the effect of enhanced recovery after surgery (ERAS) with integrated traditional Chinese and Western medicine on postoperative stress response of patients suffering from gastrointestinal tumors. Methods A total of 74 patients with gastrointestinal tumors who underwent surgical treatment in our hospital from April 2019 to March 2021 were recruited and randomized into the control group and the observation group (1 : 1). The control group received routine treatment and care, while the observation group received ERAS plus integrated traditional Chinese and Western medicine. Clinical observation was performed regarding changes in preoperative mood and postoperative pain level in each group. Changes in expression levels of plasma cortisol, C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-β (TNF-β) before and after surgery were detected in each group. Time of patients' first fart and defecation and complications after surgery in each group were recorded. Results The visual analogue scale (VAS) of patients in the observation group after 12 and 24 h of surgery was significantly lower than that in the control group (12 h: observation group 2.0 (1.00, 3.00) vs. control group 4.00 (3.00, 5.00), p = 0.001; 24 h: observation group 2.00 (1.00, 3.00) vs. control group 3.00 (2.00, 5.00), p = 0.005). The preoperative anxiety degree of patients in the two groups was not statistically significant (p = 0.489). The plasma cortisol level of patients in the observation group after 24 and 48 h of surgery was significantly lower than that in the control group (24 h: observation group 426.54 ± 52.15 nmol/L vs. control group 508.32 ± 41.08 nmol/L, p = 0.001; 48 h: observation group 287.19 ± 44.24 nmol/L vs. control group 362.57 ± 43.46 nmol/L, p = 0.001). Patients' postoperative CRP, IL-6, IL-8, and TNF-β expression levels in the observation group were remarkably lower than those in the control group at all time points. The first postoperative defecation came earlier in the observation group than that in the control group (observation group 76.00 h (64.50, 87.50) vs. control group 89.00 h (73.50, 116.00), p = 0.007). There was 1 postoperative urinary tract infection in the observation group and 1 postoperative intestinal obstruction and 1 incisional wound infection in the control group. Conclusion ERAS with integrated traditional Chinese and Western medicine could effectively reduce the postoperative stress response and inflammatory reaction in patients with gastrointestinal tumors, contributing to the safe and quick recovery of gastrointestinal functions of patients.

Development and Validation of a Risk Score for Post-Transplant Lymphoproliferative Disorders among Solid Organ Transplant Recipients.

Simple SummaryPost-transplant lymphoproliferative disease (PTLD) is a well-recognized complication after transplant. We developed and validated a risk score to predict PTLD among solid organ transplant (SOT) recipients. This work presents the first risk score developed and externally validated to predict risk of PTLD among SOT recipients. PTLD is a potentially severe complication after solid organ transplantation, and the best clinical strategy would be to detect the disease at early stages and prevent progression to fulminant lymphoma or even better to predict the risk of a patient developing PTLD prior to onset of disease. Our score had a strong similar discriminatory ability in both derivation and validation cohorts.Post-transplant lymphoproliferative disease (PTLD) is a well-recognized complication after transplant. This study aimed to develop and validate a risk score to predict PTLD among solid organ transplant (SOT) recipients. Poisson regression identified predictors of PTLD with the best fitting model selected for the risk score. The derivation cohort consisted of 2546 SOT recipients transpanted at Rigshospitalet, Copenhagen between 2004 and 2019; 57 developed PTLD. Predictors of PTLD were high-risk pre-transplant Epstein–Barr Virus (EBV), IgG donor/recipient serostatus, and current positive plasma EBV DNA, abnormal hemoglobin and C-reactive protein levels. Individuals in the high-risk group had almost 7 times higher incidence of PTLD (incidence rate ratio (IRR) 6.75; 95% CI: 4.00–11.41) compared to the low-risk group. In the validation cohort of 1611 SOT recipients from the University Hospital of Zürich, 24 developed PTLD. A similar 7 times higher risk of PTLD was observed in the high-risk group compared to the low-risk group (IRR 7.17, 95% CI: 3.05–16.82). The discriminatory ability was also similar in derivation (Harrell’s C-statistic of 0.82 95% CI (0.76–0.88) and validation (0.82, 95% CI:0.72–0.92) cohorts. The risk score had a good discriminatory ability in both cohorts and helped to identify patients with higher risk of developing PTLD.

Effects of oral N-acetyl cysteine on pain and plasma biochemical parameters in fibrocystic breast disorder: A randomized controlled trial

BackgroundFibrocystic change is the most common benign lesion in breasts of a woman in her reproductive age. It is an outcome of estrogen excess due to sex hormone imbalance. Cyclical pain as the most common symptom worsens life quality, compels patient to seek health care support continuously, and imposes large amounts of expense to both patient and health system. Current study aims to evaluate effects of N-acetyl cysteine on decreasing pain and changes in plasma biochemistry. MethodA total of 64 eligible women participated in this double-blinded randomized controlled trial. They were between 18 and 40 years. Participants were randomly allocated into oral N-acetyl cysteine and placebo receivers. Intervention and follow-up lasted for, respectively, a 12-week drugs-on and 12-month drugs-off period. Visual analog scaling was applied to measure severity of pain. Peripheral venous plasma was extracted and compared for inflammatory parameters including high-sensitivity C-reactive protein, total antioxidant capacity, malondialdehyde, total plasma glutathione, lipid profile, and fasting blood sugar. ResultsOral N-acetyl cysteine significantly decreased feeling of cyclical mastalgia (P < .01) after 12 weeks of consumption. In addition to lowering of plasma level of high-sensitivity C-reactive protein (P = .008), total plasma glutathione significantly increased (P = .02) among N-acetyl cysteine receivers. No change in lipid profile and insulin sensitivity was seen. ConclusionN-Acetyl cysteine could mitigate cyclical mastalgia. Inflammation as a considered reason for cyclical mastalgia also was halted by N-acetyl cysteine consumption.

Pulmonary Tuberculosis-Related Ischemic Stroke: A Retrospective Case Control Study.

ObjectiveThere have been only a few studies of ischemic stroke in patients with pulmonary tuberculosis (pTB). This study aimed to explore the clinical features and the underlying pathogenesis of pulmonary tuberculosis-related ischemic stroke (TBRIS).MethodsActive pulmonary tuberculosis patients with acute ischemic stroke (without conventional vascular risk factors) were recruited as the TBRIS group. Patients who solely had active pulmonary tuberculosis were recruited as the control group (pTB group). Clinical data were collected, and multiple logistic regression analysis was applied to analyze the independent risk factors for TBRIS.ResultsA total of 179 TBRIS patients and 179 pTB patients were enrolled. Most (56.42%) of the TBRIS patients experienced the ischemic stroke events within 3 months after the diagnosis of tuberculosis. The multiple logistic regression analysis revealed that an increased mean platelet volume; elevated plasma D-dimer, C-reactive protein, and serum ferritin levels; and an increased monocyte percentage were independent risk factors for TBRIS. The AUC of the identification model was 0.778, with a sensitivity of 70.30% and a specificity of 78.90%.ConclusionThe findings in the present study suggested that most of the TBRIS patients experienced ischemic stroke within 3 months after the diagnosis of tuberculosis. And the more intensive immune response to the tuberculosis infection in the TBRIS group contributed to the initiation of platelet activation and to the development of a hypercoagulable state, which were attributed to the pathogenesis of TBRIS. Index of TBRIS equaling to 0.3234 facilitates clinicians to identify the pTB patients who were at higher risk for TBRIS, and allow physicians to take further effective measures to prevent ischemic stroke in patients with pTB. However, our findings will need to be confirmed by further studies.

Significance of C-reactive Protein Levels in Categorizing Upper and Lower Urinary Tract Infection in Adult Patients.

Background: Urinary tract infections (UTIs) are one of the most commonly encountered infections in outpatients. The distinction between upper UTI and lower UTI is significant as it has therapeutic and prognostic importance. The accurate diagnosis of UTI, especially its anatomical location, is essential for administering anti-microbial therapy successfully. Plasma levels of C-reactive protein (CRP) increase 1,000-fold during bacterial infections. Elevated CRP levels are often seen in acute pyelonephritis and rarely in cystitis. Therefore, this study aimed to evaluate the diagnostic role of serum CRP in upper and lower UTI in adult patients along with correlating its role in UTI patients.Materials and methods: The study included 81 patients who were >18 years old, diagnosed with UTI by microbiological culture and ultrasonography of the pelvis. Demographic data along with findings of the systemic examination, complete blood count, random blood sugar, urine analysis, and CRP levels of all patients were recorded. Data were analyzed using R Studio.3.5.3 software, and a p-value ≤ 0.05 was considered significant.Results: The prevalence of UTI was higher among females (60.49%). About 53.09% of patients exhibited upper and 46.91% exhibited lower UTI. The prevalence of Escherichia coli was higher among cases of both upper (88.37%) and lower (65.79%) UTI. The most common final diagnosis in upper UTI patients was acute pyelonephritis (90.7%) and that in lower UTI was cystitis (65.79%). The difference in the CRP levels between the upper and lower UTI patients was significant (p=0.02). Thirty-four patients had CRP levels >100 mg/L, all exhibiting upper UTI.Conclusion: About 53.09% of patients exhibited upper UTI and were diagnosed with acute pyelonephritis. A significant increase in the CRP levels in upper UTI can help determine the anatomical location and can help in targeting effective management of the infection by anti-microbial therapy.