Nevin Manimala

J Obstet Gynaecol Res. 2022 Feb 1. doi: 10.1111/jog.15173. Online ahead of print.

ABSTRACT

AIM: The aim of this study was to determine whether there was a difference in placental metabolite profiles between patients with fetal growth restriction (FGR) and healthy controls.

METHODS: The study included 10 patients with FGR diagnosis with 14 healthy controls with both matched maternal age and body mass index. ¹ H HR-MAS NMR spectroscopy data obtained from placental tissue samples of patients with FGR and healthy control group were analyzed with bioinformatics methods. The obtained results of metabolite levels were further validated with the internal standard (IS) quantification method.

RESULTS: Principal component analysis (PCA) and the partial least squares discriminant analysis (PLS-DA) score plots obtained with the multivariate statistical analysis of preprocessed spectral data shows a separation between the samples from patients with FGR and healthy controls. Bioinformatics analysis results suggest that the placental levels of lactate, glutamine, glycerophosphocholine, phosphocholine, taurine, and myoinositol are increased in patients with FGR compared to the healthy controls.

CONCLUSIONS: Placental metabolic dysfunctions are a common occurrence in FGR.

PMID:35104920 | DOI:10.1111/jog.15173

Hematol Oncol. 2022 Feb 1. doi: 10.1002/hon.2968. Online ahead of print.

ABSTRACT

Lymphomas of the nasal cavity and paranasal sinuses (NPS) are rare. Knowledge on sinonasal B-cell lymphoma (SNBCL) primarily comes from case series or single-center studies on small cohorts. We sought to determine the subtype distribution, clinical characteristics, disease behavior, and prognosis on a nationwide scale, with an emphasis on prognostic factors for the most common sinonasal lymphoma, primary sinonasal diffuse large B-cell lymphoma (PSDLBCL). We collated all data from medical records and national databases on patients registered with SNBCL from 1980 through 2018 in the national pathology registry and collected all tissue samples for validation of diagnosis. We included 205 patients and found ten different subtypes of lymphoma. Diffuse large B-cell lymphoma (DLBCL) was the predominant subtype (80%). The incidence of sinonasal B-cell lymphoma was 0.14/100,000 person-years. The five-year progression-free survival (PFS) and overall survival (OS) rates for PSDLBCL were 50% and 56%, respectively. For PSDLBCL, Rituximab showed a statistically significant effect (Hazard Ratio 0.22, P < 0.001), whereas consolidative radiotherapy combined with immunochemotherapy was of limited value (PFS, P = 0.93). When treatment failure occurred, DLBCL showed a distinct pattern of recurrence/dissemination to the NPS, skin, breast, CNS, and/or testis. Collectively, DLBCL comprised a clear majority of SNBCLs, although nine other subtypes were represented. Data showed that immunochemotherapy increased survival for PDLBCL and that the addition of radiotherapy did not benefit patients. Furthermore, treatment failure for sinonasal DLBCL showed a possible common pathogenesis with primary extranodal lymphomas of specific locations (e.g., CNS, skin, breast, and testis). This article is protected by copyright. All rights reserved.

PMID:35104916 | DOI:10.1002/hon.2968

Surg Technol Int. 2022 Feb 2;40:sti40/1532. Online ahead of print.

ABSTRACT

BACKGROUND: Interwoven nitinol stents (INS) and drug-eluting stents (DES) were designed to improve the mid- and long-term results of femoropopliteal (F-P) angioplasty. The aim of this study was to systematically compare these stents.

METHODS: Between 2015 and 2017, 62 patients with symptomatic peripheral artery disease of the F-P segment treated by INS or DES were identified from a prospectively maintained institutional database. The primary outcome measure was one-year primary patency; secondary outcomes were in-stent restenosis (ISR), stent occlusion, target lesion revascularization (TLR) and mortality.

RESULTS: The mean follow-up was 26.9 ± 11.2 months. No statistically significant difference in primary patency at one year was observed (88.6% vs. 88.9%). Throughout follow-up, overall rates of ISR (5.7% vs. 11.1%, p = 0.645), stent occlusion (25.7% vs. 7.4%, p = 0.094) and TLR (25.7% vs. 18.5%, p = 0.505) were statistically equivalent between the groups. Mortality reached 14.3% in the INS group and 3.7% in the DES group, but this difference was not statistically significant (p=0.196). Multivariable analysis revealed significant correlations between ISR and stent occlusions; popliteal lesion localization (p = 0.016) and poor below the knee vessel outflow (p < 0.001).

CONCLUSION: In the short- and mid-term, the use of an INS or DES in the F-P arterial segment did not result in a difference in primary patency rate, stent occlusion, restenosis, re-intervention or mortality. The overall data do not provide any evidence to favor one stent over the other.

PMID:35104911

Surg Technol Int. 2022 Feb 2;40:sti40/1547. Online ahead of print.

ABSTRACT

INTRODUCTION: Opioid use disorder (OUD) patients have an increased risk of venous thromboembolism (VTE), readmissions, and higher costs following primary elective primary total joint arthroplasty, but these risks have not yet been clarified for other arthroplasty surgeries. Thus, the purpose of this study was to investigate whether OUD patients undergoing revision total knee arthroplasty (RTKA) have higher rates of: VTEs, readmissions, and costs of care.

MATERIALS AND METHODS: Patients who had a 90-day history of OUD prior to undergoing RTKA were identified and randomly matched to a comparison cohort in a 1:4 ratio by age, sex, Elixhauser-Comorbidity Index (ECI), diabetes mellitus, hyperlipidemia, hypertension, obesity, and tobacco use with a total of 16,851 patients collectively in both groups. The 90-day frequency and odds (OR) of developing VTE, deep vein thrombosis (DVTs), and PEs along with 90-day readmission rates and 90-day costs of care were analyzed. A p-value less than 0.01 was considered statistically significant.

RESULTS: OUD patients undergoing RTKA were found to have a higher incidence and odds of VTE (2.91 vs. 1.88; OR: 1.58, p<0.0001) 90 days following RTKA. Compared to the matched cohort, patients who have OUD had a higher incidence and increased risk of lower extremity DVT (2.61 vs. 1.73; OR: 1.52, p=0.0008) and PE (0.97 vs. 55%; OR: 1.74, p=0.007). Furthermore, the likelihood (25.7 vs. 21.4%; OR: 1.26, p<0.0001) of being readmitted within 90 days was higher in OUD patients. Additionally, OUD was associated with significantly higher total global 90-day episode-of-care costs ($19,289.31 ± $17,378.71 vs. $17,292.87 vs. $11,690.61; p<0.0001).

CONCLUSION: Patients who have OUD undergoing RTKA have higher rates of thromboembolic complications, readmission rates, and total global 90-day episode-of-care costs. Orthopaedic surgeons should educate OUD patients about these risks and titrate patient opioid consumption through multi-specialty interventions prior to surgery to improve outcomes and reduce costs.

PMID:35104910

Pediatrics. 2022 Jan 1;149(1):e2021053655. doi: 10.1542/peds.2021-053655.

NO ABSTRACT

PMID:35104887 | DOI:10.1542/peds.2021-053655

Nucleic Acids Res. 2022 Feb 1:gkac029. doi: 10.1093/nar/gkac029. Online ahead of print.

ABSTRACT

Proteins isolated from natural sources can be composed of a mixture of isoforms with similar physicochemical properties that coexist in the final steps of purification. Yet, even where unverified, the assumed sequence is enforced throughout the structural studies. Herein, we propose a novel perspective to address the usually neglected sequence heterogeneity of natural products by integrating biophysical, genetic and structural data in our program SEQUENCE SLIDER. The aim is to assess the evidence supporting chemical composition in structure determination. Locally, we interrogate the experimental map to establish which side chains are supported by the structural data, and the genetic information relating sequence conservation is integrated into this statistic. Hence, we build a constrained peptide database, containing most probable sequences to interpret mass spectrometry data (MS). In parallel, we perform MS de novo sequencing with genomic-based algorithms to detect point mutations. We calibrated SLIDER with Gallus gallus lysozyme, whose sequence is unequivocally established and numerous natural isoforms are reported. We used SLIDER to characterize a metalloproteinase and a phospholipase A2-like protein from the venom of Bothrops moojeni and a crotoxin from Crotalus durissus collilineatus. This integrated approach offers a more realistic structural descriptor to characterize macromolecules isolated from natural sources.

PMID:35104880 | DOI:10.1093/nar/gkac029

J Infect Dis. 2022 Feb 1:jiac032. doi: 10.1093/infdis/jiac032. Online ahead of print.

ABSTRACT

BACKGROUND: Analytical treatment interruptions (ATI) are pauses of antiretroviral therapy (ART) in the context of HIV cure trials. They are the gold standard in determining if interventions being tested can achieve sustained virological control in the absence ART. However, withholding ART comes with risks and discomforts to the trial participant. We used mathematical models to explore how ATI study design can be improved to maximise statistical power, while minimising risks to participants.

METHODS: Using previously observed dynamics of time to viral rebound (TVR) post ATI, we modelled estimates for optimal sample size, frequency and ATI duration required to detect a significant difference in the TVR between control and intervention groups. Groups were compared using a log-rank test, and analytical and stochastic techniques.

RESULTS: In placebo controlled TVR studies, 120 participants are required in each arm to detect 30% difference in the frequency of viral reactivation at 80% power. There was little statistical advantage to measuring viral load more frequently than weekly, or interrupting ART beyond 5 weeks in a TVR study.

CONCLUSIONS: Current TVR HIV cure studies are underpowered to detect statistically significant changes in frequency of viral reactivation. Alternate study designs can improve the statistical power of ATI trials.

PMID:35104873 | DOI:10.1093/infdis/jiac032

Nature. 2022 Feb 1. doi: 10.1038/s41586-022-04462-1. Online ahead of print.

ABSTRACT

The emergence of a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Omicron, is an urgent global health concern (ref.¹). Our statistical modelling suggests that Omicron has spread more rapidly than the Delta variant in several countries including South Africa. Cell culture experiments show that Omicron is less fusogenic than Delta and an ancestral SARS-CoV-2 strain. Although the spike (S) protein of Delta is efficiently cleaved into two subunits, which facilitates cell-cell fusion^2,3, Omicron S is less efficiently cleaved compared to Delta S and ancestral SARS-CoV-2 S. Furthermore, in a hamster model, Omicron shows decreased lung infectivity and is less pathogenic compared to Delta and ancestral SARS-CoV-2.

PMID:35104835 | DOI:10.1038/s41586-022-04462-1

Urol Int. 2022 Feb 1:1-6. doi: 10.1159/000521660. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate toxicity, oncological and functional outcome, and quality of life after salvage radiotherapy for recurrent prostate cancer after high-intensity focused ultrasound (HIFU) therapy.

METHODS: A total of 13 patients undergoing salvage radiotherapy for biopsy-proven prostate cancer recurrence after HIFU therapy were included and followed up every 3 months. Oncological outcome (by PSA measurements), toxicity (according to CTCAE criteria), and functional outcome were evaluated. Quality of life was assessed by standardized questionnaires (QLQ-C30 and QLQ-PR25) at baseline, 3 months, and 12 months after salvage treatment.

RESULTS: Median age of patients was 80 years (interquartile range [IQR] 75-82). Patients underwent normofractionated salvage radiotherapy with median 73.6 Gy. PSA nadir was reached at 6 months and was 0.2 ng/mL. Median follow-up was 76 months (IQR 55-96). Biochemical recurrence occurred in 3 patients (23.1%) at a median of 36.4 months. No gastrointestinal (GI) or genitourinary (GU) toxicity ≥ grade 3 was noted during follow-up. Early and late grade II GI toxicity occurred in 1 patient (7.7%), respectively. GU toxicity grade II was noted in up to 53.8% at 3 months and 61.5% at 12 months. In terms of health-related quality of life, there was no statistically significant difference at 3 and 12 months compared to the baseline. Only differences were seen in sexual functioning (3 and 12 months) and in diarrhea (3 months), affecting patients’ wellbeing.

DISCUSSION/CONCLUSION: Salvage radiotherapy after HIFU treatment can be performed safely, thereby providing acceptable recurrence-free survival without severe impact on post-interventional quality of life.

PMID:35104820 | DOI:10.1159/000521660

Ecotoxicol Environ Saf. 2022 Jan 28;232:113254. doi: 10.1016/j.ecoenv.2022.113254. Online ahead of print.

ABSTRACT

China is the largest producer and consumer of plastics worldwide. Microplastic (MP) pollution has been a recent research hotspot in environmental science and ecology. This study collects and analyzes the statistical data for microplastics (MPs) 86 lakes in entire China’s lake ecosystems in past five years (2016-2020), their range in area is 0.056-4543.000 km² (average: 566.045 km²), and the water storage varies from 0.162 × 10⁸ to 1050.000 × 10⁸ m³ (average: 77.884 ×10⁸ m³). The results showed (1) The MP abundance in lake surface water is significantly correlated with lake area (ρ = -0.562, p ＜0.01), provincial GDP (Gross Domestic Product, GDP) (ρ = 0.377, p = 0.002), GDP per capita (ρ = 0.346, p = 0.006), urban waste water discharge and ratio of agricultural land area (ρ = 0.369, p = 0.003). (2) The MP abundance in lake sediment is significantly correlated with per capita domestic volume of garbage disposal (ρ = -0.536, p ＜0.001), per capita urban waste water discharge (ρ = -0.544, p ＜0.001) and ratio of agricultural land area (ρ = 0.635, p ＜0.001). (3) Irrespective of whether the samples were from surface water or sediment, MPs were primarily transparent, and the dominant types were fragments, films, and fibers. In addition, the size of MPs samples was mostly less than 2 mm, and the major polymers were polyethylene (PE), polypropylene (PP), and polystyrene (PS). (4) The degree of MP pollution in organisms was related to the degree of environmental pollution. These findings could provide a theoretical basis for the control and management of MP pollution in China’s lake ecosystems.

PMID:35104781 | DOI:10.1016/j.ecoenv.2022.113254