Nevin Manimala

Mult Scler Relat Disord. 2021 Nov 22;57:103417. doi: 10.1016/j.msard.2021.103417. Online ahead of print.

ABSTRACT

BACKGROUND: Various studies indicated blunted humoral responses to COVID-19 mRNA and viral vector vaccines among people with multiple sclerosis (pwMS) on sphingosine 1-phosphate receptor (S1PR) modulators and anti-CD20 therapies (aCD20); however, limited evidence was found regarding SARS-CoV-2 serology after inactivated virus vaccination.

OBJECTIVE: To provide evidence regarding humoral response to COVID-19 inactivated virus vaccination among pwMS on disease-modifying therapies (DMTs).

METHODS: A cohort study was carried out in Isfahan, Iran, enrolling DMT-exposed pwMS and unexposed (UX) healthy participants. Post-vaccination anti-SARS-CoV-2 Spike IgG serology testing was carried out among the participants and compared between participants based on their DMT exposure, using proper statistical tests. A multivariable logistic regression model was used to control for confounding. Association between the second vaccine dose-to-phlebotomy (vac2phleb) and the humoral response was investigated in each DMT-exposed cohort, using linear regression. Among the aCD20 cohort, the association of the last aCD20 infusion-to-first vaccine dose period with serostatus was investigated using an unpaired t-test.

RESULTS: After enrolling 358 participants (144 pwMS and 214 healthy), blunted humoral responses were only observed in fingolimod (Log₁₀ mean diff. [SE]: 0.72 [0.18], P = 0.001) and aCD20 (Log₁₀ mean diff. [SE]: 0.75 [0.15], P < 0.001) cohorts compared to the UX cohort. Multivariable analysis confirmed the results. The study did not achieve enough statistical power to detect a significant association between the vac2phleb period and humoral responses. The last aCD20 infusion to first vaccination dose period was longer in the seroconverted pwMS on aCD20 (mean diff. [SE]: 8.43 weeks [2.57], P = 0.005).

CONCLUSION: The results of this study mirrored the results of previous studies among mRNA- or viral vector-vaccinated pwMS on DMTs. Therefore, it can be concluded that mode of action contributes less than timing, to the efficiency of vaccination strategies among pwMS on DMTs – especially the ones on S1PR modulators and aCD20. Meanwhile, the mentioned pwMS should be advised to receive early boosters and remain vigilant until further data becomes available and more efficient vaccination strategies are crafted.

PMID:34875487 | DOI:10.1016/j.msard.2021.103417

Eur J Radiol. 2021 Dec 1;146:110080. doi: 10.1016/j.ejrad.2021.110080. Online ahead of print.

ABSTRACT

PURPOSE: Computed tomography (CT) might be a good diagnostic test to accurately quantify calcium in vascular beds but there are multiple factors influencing the quantification. The aim of this study was to investigate the influence of different computed tomography protocol settings in the quantification of calcium in the lower extremities using modified Agatston and volume scores.

METHODS: Fresh-frozen human legs were scanned at different tube current protocols and reconstructed at different slice thickness. Two different iterative reconstruction protocols for conventional CT images were compared. Calcium was manually scored using modified Agatston and volume scores. Outcomes were statistically analyzed using Wilcoxon signed-rank tests and mean absolute and relative differences were plotted in Bland-Altman plots.

RESULTS: Of the 20 legs, 16 had CT detectable calcifications. Differences between thick and thin slice reconstruction protocols were 129 Agatston units and 125% for Agatston and 78.4 mm³ and 57.8% for volume (all p ≤ 0.001). No significant differences were found between low and high tube current protocols. Differences between iDose⁴ and IMR reconstruction protocols for modified Agatston were 34.2 Agatston units and 17.7% and the volume score 33.5 mm³ and 21.2% (all p ≤ 0.001).

CONCLUSIONS: Slice thickness reconstruction and reconstruction method protocols influenced the modified Agatston and volume scores in leg arteries, but tube current and different observers did not have an effect. This data emphasizes the need for standardized quantification of leg artery calcifications. Possible implications are in the development of a more universal quantification method, independent of the type of scan and vasculature.

PMID:34875474 | DOI:10.1016/j.ejrad.2021.110080

Cancer Treat Res Commun. 2021 Nov 26;29:100495. doi: 10.1016/j.ctarc.2021.100495. Online ahead of print.

ABSTRACT

OBJECTIVES: Early diagnosis of lung cancer increases the chance of survival. The aim of this study was to measure the relationship between geographic residence in Saskatchewan and stage of lung cancer at the time of diagnosis.

MATERIALS AND METHODS: Retrospective cohort analysis of 2,972 patients with a primary diagnosis of either non-small cell cancer (NSCLC) or small cell lung cancer (SCLC) between 2007 and 2012 was performed. Incidence proportion of early and advanced stage cancer, and relative risk of being diagnosed with advanced-stage lung cancer relative to early-stage was calculated.

RESULTS: Compared to urban Saskatchewan, rural Saskatchewan lung cancer patients had a higher relative risk of advanced stage NSCLC (relative risk [RR] = 1.11, 95% confidence interval [CI]: 1.01-1.22). Rural Saskatchewan was further subdivided into north and south. The relative risk of advanced stage NSCLC in rural north Saskatchewan compared to urban Saskatchewan was even greater (RR = 1.17, 95% CI: 1.03-1.31). Although not statistically significant, there was a trend for a higher incidence of advanced stage SCLC in rural and rural north vs urban Saskatchewan (RR = 1.16, 95% CI: 0.95-1.43 and RR = 1.22; 95% CI: 0.94-1.58, respectively). There was a higher incidence proportion of advanced stage NSCLC in rural areas relative to urban (31.6-34.4 vs 29.5 per 10,000 people).

CONCLUSION: Patients living in rural Saskatchewan have higher incidence proportion of and were more likely to present with advanced stage NSCLC in comparison to urban Saskatchewan patients at time of diagnosis. This inequality was even greater in rural north Saskatchewan.

PMID:34875463 | DOI:10.1016/j.ctarc.2021.100495

Value Health Reg Issues. 2021 Dec 4;29:86-92. doi: 10.1016/j.vhri.2021.09.003. Online ahead of print.

ABSTRACT

OBJECTIVES: The technological advancement in the field of orthopedics has initiated better healthcare service that equates to the need of cost-effectiveness approach. We propose a model for estimating the simultaneous effect of health and cost involved in an orthopedic surgery implants by using seemingly unrelated regression equations models.

METHODS: The simultaneous equations represent a relationship between the health status of a group of individuals and their expenditures related to the cost of surgical procedure/treatment undertaken in an orthopedic department of a hospital. We define model specification, estimation, and statistical tests in simultaneous equation models. This is further used to estimate the utility function that indeed helps in the computation of quality-adjusted life-year (QALY) values.

RESULTS: Using the seemingly unrelated regression equation models for the seasonal data in 2018 and 2019, we have obtained the seasonal QALY values. Furthermore, the measurement of seasonal changes in QALY values is done by using a method of simple averages.

CONCLUSIONS: We analyze the health conditions in orthopedics by the formation of health and expenditure relationship for the inpatients and outpatients undertaking a treatment. A framework has been setup for computing quality of life-year values by including the direct and the indirect costs. The patient-reported outcome measures are also useful in detecting the change in disease states and important difference in minimal clinical changes that further adds value to the computation of quality of life.

PMID:34875450 | DOI:10.1016/j.vhri.2021.09.003

Am J Obstet Gynecol MFM. 2021 Dec 4:100541. doi: 10.1016/j.ajogmf.2021.100541. Online ahead of print.

ABSTRACT

BACKGROUND: Postpartum anemia is common after delivery, and postpartum blood transfusion is the leading indicator of Severe Maternal Morbidity in the United States. While hematologic changes during the antepartum period are well understood, less is known about postpartum hematologic changes. We investigated hematologic changes in the postpartum period in a large, contemporary cohort.

OBJECTIVE: To characterize postpartum period hematologic recovery and evaluate the effect of demographics, medical conditions, and pregnancy characteristics on the recovery.

STUDY DESIGN: In a contemporary cohort of deliveries in 2019 at a single institution, the hematocrit of postpartum women prior to hospital discharge was compared to hematocrit at the postpartum follow-up. Our population was composed of a predominantly Hispanic population at an urban, safety net hospital. All women receive a CBC on postpartum day one and a spun hematocrit at their postpartum follow-up visit in our hospital system. All women are scheduled for a routine postpartum visit 2-3 weeks postpartum. All deliveries of a liveborn infant with available postpartum hematocrit prior to hospital discharge and at postpartum follow-up were included. Demographics and pregnancy characteristics, along with medical conditions were evaluated. To evaluate an uncomplicated cohort, those with multiple gestation, preeclampsia with severe features, chronic hypertension, and diabetes were excluded in secondary analysis. Statistical analysis included chi-square, paired Student’s t-test, Student’s t-test for independent groups, and analysis of variance.

RESULTS: Of the 12,456 deliveries, 9,003 met inclusion criteria. The average number of days from discharge to follow-up was 21.73±10.39 days. The average hematocrit prior to discharge was 30.77±3.61 and at postpartum follow-up 38.70±3.61. Hematocrit increased from discharge to postpartum follow-up an average of 7.93±3.24. In the cohort without complications, the average increase in hematocrit was 8.19±3.09. The rise of hematocrit was significantly lower for those with chronic hypertension (6.9±3.6%), diabetes (7.3±3.3%), and preeclampsia with severe features (6.9±3.7%). The severity of anemia influenced the rise in hematocrit in the postpartum period. In women with postpartum anemia (hematocrit <30%), the rise in hematocrit was 9.49±2.97 in the uncomplicated cohort. Postpartum hemorrhage did not influence rise in postpartum hematocrit; women receiving blood transfusion had a greater rise in hematocrit (9.01±3.29).

CONCLUSION: Our study establishes the natural course of hematologic recovery in the postpartum period, and we found women with asymptomatic postpartum anemia will have a hematocrit of 37-39% at their postpartum follow-up approximately 3 weeks after hospital discharge. Women with pre-existing and obstetric complications experience less hematologic recovery and adapt more slowly to postpartum physiological changes.

PMID:34875414 | DOI:10.1016/j.ajogmf.2021.100541

J Clin Epidemiol. 2021 Dec 4:S0895-4356(21)00396-6. doi: 10.1016/j.jclinepi.2021.11.038. Online ahead of print.

NO ABSTRACT

PMID:34875377 | DOI:10.1016/j.jclinepi.2021.11.038

Brain Behav Immun. 2021 Dec 4:S0889-1591(21)00622-X. doi: 10.1016/j.bbi.2021.11.019. Online ahead of print.

ABSTRACT

BACKGROUND: Peripheral inflammation is implicated in schizophrenia, however, not all individuals demonstrate inflammatory alterations. Recent studies identified inflammatory subtypes in chronic psychosis with high inflammation having worse cognitive performance and displaying neuroanatomical enlargement compared to low inflammation subtypes. It is unclear if inflammatory subtypes exist earlier in the disease course, thus, we aim to identify inflammatory subtypes in antipsychotic naïve First-Episode Schizophrenia (FES).

METHODS: 12 peripheral inflammatory markers, clinical, cognitive, and neuroanatomical measures were collected from a naturalistic study of antipsychotic-naïve FES patients. A combination of unsupervised principal component analysis and hierarchical clustering was used to categorize inflammatory subtypes from their cytokine data (17 FES High, 30 FES Low, and 33 healthy controls (HCs)). Linear regression analysis was used to assess subtype differences. Neuroanatomical correlations with clinical and cognitive measures were performed using partial Spearman correlations. Graph theoretical analyses were performed to assess global and local network properties across inflammatory subtypes.

RESULTS: The FES High group made up 36% of the FES group and demonstrated significantly greater levels of IL1β, IL6, IL8, and TNFα compared to FES Low, and higher levels of IL1β and IL8 compared to HCs. FES High had greater right parahippocampal, caudal anterior cingulate, and bank superior sulcus thicknesses compared to FES Low. Compared to HCs, FES Low showed smaller bilateral amygdala volumes and cortical thickness. FES High and FES Low groups demonstrated less efficient topological organization compared to HCs. Individual cytokines and/or inflammatory signatures were positively associated with cognition and symptom measures.

CONCLUSIONS: Inflammatory subtypes are present in antipsychotic-naïve FES and are associated with inflammation-mediated cortical expansion. These findings support our previous findings in chronic psychosis and point towards a connection between inflammation and blood-brain barrier disruption. Thus, identifying inflammatory subtypes may provide a novel therapeutic avenue for biomarker-guided treatment involving anti-inflammatory medications.

PMID:34875344 | DOI:10.1016/j.bbi.2021.11.019

Sci Total Environ. 2021 Dec 4:152162. doi: 10.1016/j.scitotenv.2021.152162. Online ahead of print.

ABSTRACT

Anthropogenic pollutants (organic nitrogen and ammonia) can change the dynamic balances of hydrogeochemical components of groundwater, and this can affect the fates of the pollutants and groundwater quality. The aim of this paper is to assess the long-term impact of pollutants on groundwater component concentrations and species in three sites that has been polluted with illegal discharge wastewater containing organic nitrogen and ammonia, in order to reveal the interactions between nitrogen species and Mn. We analyzed semi-monthly groundwater data from three sites in northwestern China over a long period of time (2015-2020) by using statistical analyses, correlation analyses, and a correlation co-occurrence network method. The results showed that wastewater entering groundwater from surface changed the hydrogeochemical component concentrations and species significantly. The main form of inorganic nitrogen species changed from nitrate to ammonia. The Mn concentration increased from undetectable (<0.01 mg/L) to 1.64 mg/L (the maximum), which surpassed the guideline value suggested by China and WHO. The main mechanism for Mn increase is the reductive dissolution of Mn oxide caused by the oxidation of organic nitrogen. Mn‑nitrogen species interaction complicates the transformation of nitrogen components. Chemoautotrophic denitrification and dissimilatory nitrate reduction to ammonium (DNRA) mediated by Mn are the major mechanisms of nitrate attenuation when dissolved oxygen is greater than 2 mg/L. Mn oxides reductive dissolution and reoxidation of Mn by nitrate reduction cause Mn to circulate in groundwater. The results provide field evidence for interactions between nitrogen species transformation and Mn cycle in groundwater. This has important implications for pollution management and groundwater remediation, particularly monitored natural attenuation.

PMID:34875327 | DOI:10.1016/j.scitotenv.2021.152162

J Intern Med. 2021 Dec 7. doi: 10.1111/joim.13420. Online ahead of print.

ABSTRACT

Colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy is a rare but fatal microgliopathy. The diagnosis is often delayed due to multifaceted symptoms that can mimic several other neurological disorders. Imaging provides diagnostic clues that help identify cases. The objective was to integrate the literature on neuroimaging phenotypes of CSF1R-related leukoencephalopathy. A systematic review and meta-analysis were performed for neuroimaging findings of CSF1R-related leukoencephalopathy via PubMed, Web of Science, and Embase on August 25^th , 2021. The search included cases with confirmed CSF1R-mutations reported under the previous terms hereditary diffuse leukoencephalopathy with spheroids (HDLS), pigmentary orthochromatic leukodystrophy (POLD), and adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). The results: In 78 studies providing neuroimaging data, 195 cases were identified carrying CSF1R mutations in 14 exons and 5 introns. Women had a statistically significant earlier age of onset (p = 0.041, 40 vs. 43 years). Mean delay between symptom onset and neuroimaging was 2.3 years. Main magnetic resonance imaging (MRI) findings were frontoparietal white matter lesions, callosal thinning and foci of restricted diffusion. The hallmark computed tomography (CT) finding was white matter calcifications. Widespread cerebral hypometabolism and hypoperfusion were reported using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Conclusions: CSF1R-related leukoencephalopathy is associated with progressive white matter lesions and brain atrophy that can resemble other neurodegenerative/-inflammatory disorders. However, long-lasting diffusion restriction and parenchymal calcifications are more specific findings that can aid the differential diagnosis. Native brain CT and brain MRI (with and without contrast-agent) are recommended with proposed protocols and pictorial examples provided. This article is protected by copyright. All rights reserved.

PMID:34875121 | DOI:10.1111/joim.13420

Pacing Clin Electrophysiol. 2021 Dec 7. doi: 10.1111/pace.14416. Online ahead of print.

ABSTRACT

AIMS: Goal of Transvenous Lead Extraction (TLE) is complete removal of all targeted leads, without complications. Despite counter traction manoeuvres, efficacy rates are often hampered by broken right ventricle lead (RV-lead) tips. Mechanically powered lead extraction (Evolution sheath) is effective, however safety of dissection up to the lead tip is unclear. Therefore, we examined the feasibility and safety of RV-lead extraction requiring dissection up to the myocardium.

METHODS AND RESULTS: From 2009 to 2018, all TLE in the Isala Heart Centre (Zwolle, The Netherlands) requiring the hand-powered mechanical Evolution system to extract RV-leads (n = 185) were examined from a prospective registry. We assessed 4 groups: TLE with the first generation Evolution (n = 43) with (A1,n = 18) and without (A2,n = 25) adhesions up to the myocardium and TLE with the Novel R/L type (n = 142) of sheath with (B1, n = 59) and without (B2, n = 83) adhesions up to the myocardium. Complete success rate in Group B was significantly higher than group A (96.5 vs 76.7%, p = 0.0354). When comparing the patients with adhesions up to the myocardium, total complete success is higher in the R/L group (61.1% vs 90.5%, p = 0.0067). There were no deaths. Overall major complication rates were low (2/185; 1.1%) and there was no statistically significant difference in major and minor complications between the two groups.

CONCLUSION: Extraction strategy with the bidirectional Evolution R/L sheath for right ventricular leads with adhesions up to the myocardium is safe and feasible. This article is protected by copyright. All rights reserved.

PMID:34875112 | DOI:10.1111/pace.14416