Tag: pubmed

Clin Transl Oncol. 2021 Feb 24. doi: 10.1007/s12094-021-02569-x. Online ahead of print.

ABSTRACT

BACKGROUND: The study examines the function of hypoxia-mediated down-regulation of microRNAs (miRNAs) (mir-30c, mir-135a, and mir-27a) in the process of bladder cancer immune escape.

METHODS: Quantitative Real-time PCR (qRT-PCR) was carried out to determine gene expression levels of Drosha and Dicer under hypoxia treatment, while western blotting and flow cytometry were used to determine protein expression. Seven reported miRNAs were identified via qRT-PCR assay. Flow cytometry detection of CD3/CD4/CD8-positive expression and statistics. Enzyme-linked immunosorbent assay (ELISA) detected cellular immune factors content. Cell apoptosis was checked via flow cytometry assay. Luciferase report assay and western blot assays were both used to verify the relationship between miRNAs and Casitas B-lineage lymphoma proto-oncogene b (Cbl-b). The animal model was established and Hematoxylin-eosin (HE) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunohistochemistry (IHC) assays were separately used to verify the conclusions.

RESULTS: The CD3 + /CD4 + expression was increased in the hypoxia group, while CD3 + /CD8 + expression, the cellular immune factors content Interleukin-2 (IL-2) and Tumor Necrosis Factor-α (TNFα) along with the cell apoptosis were suppressed. The protein expression of Cbl-b was found to be up-regulated in the hypoxia group. After constructing the overexpression/ knockdown of Cbl-b in peripheral blood mononuclear cell (PBMC), Cbl-b has been found to promote tumor immune escape in bladder cancer. Furthermore, Cbl-b had been identified as the co-targets of mir-30c, mir-135a, and mir-27a and down-regulation of miRNA biogenesis promotes Cbl-b expression and deactivating T cells in vitro/in vivo.

CONCLUSION: Hypoxia-mediated down-regulation of miRNAs’ biogenesis promotes tumor immune escape in bladder cancer, which could bring much more advance to the medical research on tumors.

PMID:33625672 | DOI:10.1007/s12094-021-02569-x

J Neurol. 2021 Feb 24. doi: 10.1007/s00415-021-10475-z. Online ahead of print.

ABSTRACT

BACKGROUND: Late-onset Pompe disease (LOPD) is a rare autosomal recessive disorder caused by mutations in the GAA gene, leading to progressive weakness of locomotor and respiratory muscles. Enzyme replacement therapy (ERT), administered every second week, has been proven to slow down disease progression and stabilize pulmonary function. Due to the COVID-19 pandemic in Germany, ERT was interrupted at our centre for 29 days. As reports on ERT discontinuation in LOPD are rare, our study aimed to analyse the impact of ERT interruption on the change in clinical outcome.

METHODS: We performed a prospective cohort study in 12 LOPD patients. Clinical assessments were performed after ERT interruption and after the next three consecutive infusions. We assessed motor function by muscle strength testing, a 6-minute-walk-test, pulmonary function tests, and adverse events. For statistical analysis, an estimated baseline was calculated based on the individual yearly decline.

RESULTS: The mean time of ERT interruption was 49.42 days (SD ± 12.54). During ERT interruption, seven patients reported 14 adverse events and two of them were severe. Frequent symptoms were reduced muscle endurance/increased muscle fatigability and shortness of breath/worsening of breathing impairment. After ERT interruption, significant deterioration was found for MIP_%pred (p = 0.026) and MRC_%pred, as well as a trend to clinical deterioration in FVC_%pred and the 6MWT_%pred.

CONCLUSION: Interruption of ERT was associated with a deterioration in the core clinical outcome measures. Therefore, an interruption of ERT should be kept as short as possible.

PMID:33625582 | DOI:10.1007/s00415-021-10475-z

J Orthop Traumatol. 2021 Feb 24;22(1):4. doi: 10.1186/s10195-021-00569-9.

ABSTRACT

BACKGROUND: External fixation is the primary treatment option in children for femoral shaft fractures, such as open femoral or multiple fractures. One complication is refracture, which is the biggest limitation of fixation devices. This study aims to investigate the risk factors associated with refracture after the removal of external fixation devices and decrease the frequency of refracture.

MATERIALS AND METHODS: Retrospectively reviewed clinical data of 165 patients treated at our hospital for fresh femoral shaft fractures with external fixation between May 2009 and February 2018 were included in this study. Patients with pathological fractures, fractures of the femoral neck, fractures that were fixed using plates or elastic stable intramedullary nailing, and old fractures, as well as those who underwent postoperative femoral surgery were excluded. Potential risk factors included: patient age, gender, and weight, fracture sides, open or closed fracture, fracture sites, reduction methods, operation time, perioperative bleeding, number and diameter of the screws, and immobilization time. These factors were identified by univariate and logistic regression analyses.

RESULTS: Femoral shaft refracture developed in 24 patients. Univariate analysis revealed that refracture was not statistically significantly associated with any of the above factors, except AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF) classification type 32-D/4.2 and L2/L3 ratio (L2, length of femur fixed by the two screws farthest from the fracture line; L3, the total length from the greater trochanter to the distal end of femur; P < 0.001 and P = 0.0141, respectively). Multivariate analysis showed that PCCF classification type 32-D/4.2 and L2/L3 ratio were also independent risk factors for femoral refracture.

CONCLUSIONS: Femoral shaft refracture is relatively common in children treated with external fixation. Because of the limited number of cases in this study, we cautiously concluded that the PCCF classification type 32-D/4.2 and L2/L3 ratio were independent risk factors for femoral shaft refracture in these patients.

LEVEL OF EVIDENCE: IV.

PMID:33625585 | DOI:10.1186/s10195-021-00569-9

Surg Endosc. 2021 Feb 24. doi: 10.1007/s00464-021-08374-5. Online ahead of print.

ABSTRACT

BACKGROUND: Revisional surgery after failed laparoscopic sleeve gastrectomy (LSG) is growing and laparoscopic one anastomosis gastric bypass (LOAGB) has been proposed as a revisional procedure due to its combined restrictive and malabsorptive effects. The aim is to study short-term complications and weight loss (WL) results of the revisional LOAGB after LSG for the two-weight loss failure (WLF) types [insufficient weight loss (IWL) and weight regain (WR)] and to assess the possible effects of these two types of failure and gastric tube anatomy on the final outcome.

METHODS: The data of 28 patients who completed 1-year follow-up for their revisional LOAGB after their failed LSG were assessed and statistically correlated to leakage and one year WL results.

RESULTS: Operative time was 96 ± 17.4 min. Leakage occurred in 2 patients (7.1%); the small number of leak patients does not allow statistical analysis for leakage. Percentage of excess weight loss (%EWL) at one year was 79.0 ± 14.4%; percentage of total weight loss (%TWL) was 31.7 ± 6.4%. %EWL was 84.2 ± 13.1 with IWL and 73.0 ± 13.9 with WR (P = 0.036). %TWL was 35.0 ± 5.2 with IWL and 27.8 ± 5.5 with WR (P = 0.001). %TWL at persistent fundus, diffusely dilated, and nondilated stomach were 38.98 ± 4.57, 31.3 ± 5.33, and 28.54 ± 5.91, respectively (P = 0.006).

CONCLUSION: LOAGB is a highly effective and safe procedure as a revision after LSG with WLF. Patients with IWL and patients with persistent fundus lost more weight than those with WR and those with diffuse stomach dilation or nondilation, respectively.

PMID:33625589 | DOI:10.1007/s00464-021-08374-5

Environ Monit Assess. 2021 Feb 24;193(3):142. doi: 10.1007/s10661-021-08875-9.

ABSTRACT

Phosphorus (P) load apportionment models (LAMs), requiring only spatially and temporally paired P and flow (Q) measurements, provide outputs of variable accuracy using long-term monthly datasets. Using a novel approach to investigate the impact of catchment characteristics on accuracy variation, 91 watercourses’ Q-P datasets were applied to two LAMs, BM and GM, and bootstrapped to ascertain standard errors (SEs). Random forest and regression analysis on data pertaining to catchments’ land use, steepness, size, base flow and sinuosity were used to identify the individual relative importance of a variable on SE. For BM, increasing urban cover was influential on raising SEs, accounting for c.19% of observed variation, whilst analysis for GM found no individually important catchment characteristic. Assessment of model fit evidenced BM consistently outperformed GM, modelling P values to ±10% of actual P values in 85.7% of datasets, as opposed to 17.6% by GM. Further catchment characteristics are needed to account for SE variation within both models, whilst interaction between variables may also be present. Future research should focus on quantifying these possible interactions and should expand catchment characteristics included within the random forest. Both LAMs must also be tested on a wide range of high temporal resolution datasets to ascertain if they can adequately model storm events in catchments with diverse characteristics.

PMID:33625605 | DOI:10.1007/s10661-021-08875-9

Cancer Immunol Immunother. 2021 Feb 24. doi: 10.1007/s00262-021-02888-6. Online ahead of print.

ABSTRACT

BACKGROUND: Sarcopenia has been associated with negative clinical outcomes in cancer patients, particularly response to treatment and survival. The exponential growth in the use of immune checkpoint inhibitors (ICIs) has led to an increase in the reporting of both adverse events in general (AEs) and immune-related adverse events (irAEs), which are unintended immune-related phenomenon that take place as a result of checkpoint blockade. However, there are no systematic reviews evaluating the relationship between sarcopenia and the risk of developing AEs and irAEs in cancer patients on ICI therapies.

METHODS: PubMed, MEDLINE, Embase, Cochrane and grey literature, repositories, websites Open Grey, Google Scholar, and abstracts of major international congresses were searched up to April 2020 for observational studies on sarcopenia and both AEs and irAEs in patients treated with ICIs. Study quality was assessed with The Newcastle-Ottawa quality assessment scale. PROSPERO registration number: CRD42020197178.

RESULTS: One hundred and thirteen discrete articles were identified. Seven studies were included after evaluation of the eligibility criteria. Important sources of heterogeneity including the specific cut-points defining sarcopenia, sample size, inclusion and exclusion criteria, treatment regimen, and baseline demographics were evaluated and accounted for accordingly.

CONCLUSION: Most of the included studies showed an increased risk of AEs with use of ICIs in cancer patients with sarcopenia, and in the majority of these, the increase was statistically significant. Due to the small number of available studies and the expanding use of ICIs, additional research is warranted.

PMID:33625531 | DOI:10.1007/s00262-021-02888-6

Rheumatol Int. 2021 Feb 24. doi: 10.1007/s00296-021-04791-w. Online ahead of print.

ABSTRACT

To study the association of smoking status and the level of seropositivity in RA patients from COMORA Cohort. A post hoc analysis of COMORA database included 3439 RA patients was performed. Current smokers or recently quitted (< 3 years) were initially compared to those who never smoked or stopped > 3 years (Group I vs. II) regarding their seropositivity status (high positive, low positive and negative) for Rheumatoid Factor (RF) or Anti-citrullinated antibodies (ACPA). A further comparison was made between current smokers (Group III) and never smoked patients (Group IV). Analysis was also done on the individual country level for the 17 countries included in the COMORA study. Out of 3439 RA patients, 705 (20.5%) were smokers (group I), and 2734 (79.5%) were non-smokers (group II). Significantly more patients in group I, 442 (62.7%), had high levels of seropositivity than those in group II, 1556 (56.9%), [P = 0.006, OR 1.27 (95% CI, 1.07-1.5)]. More current smoker patients (group III-286 out of 456 “62.7%”) had high levels of seropositivity than never smoked patients (group IV-1236 out of 2191 “56.4%”), with significant difference [P = 0.013, OR 1.3 (95% CI, 1.06-1.6)]. In 11 countries, higher proportions of patients with high level of seropositivity in group I was found, with statistical significance in four countries. Smoking was associated with higher level of seropositivity in patients with RA in this post hoc analysis, both on a global level and in certain individual countries. As smoking is a modifiable risk factor, studying the effects of quitting smoking on level of seropositivity and other disease parameters is warranted.

PMID:33625544 | DOI:10.1007/s00296-021-04791-w

Neuroradiology. 2021 Feb 24. doi: 10.1007/s00234-021-02676-0. Online ahead of print.

ABSTRACT

PURPOSE: Results of surgical or endovascular treatment of intracranial aneurysms are often assessed using angiography. A reliable method to report results irrespective of treatment modality is needed to enable comparisons. Our goals were to systematically review existing classification systems, and to propose a 3-point classification applicable to both treatments and assess its reliability.

METHODS: We conducted two systematic reviews on classification systems of angiographic results after clipping or coiling to select a simple 3-category scale that could apply to both treatments. We then circulated an electronic portfolio of angiograms of clipped (n=30) or coiled (n=30) aneurysms, and asked raters to evaluate the degree of occlusion using this scale. Raters were also asked to choose an appropriate follow-up management for each patient based on the degree of occlusion. Agreement was assessed using Krippendorff’s α statistics (α_K), and relationship between occlusion grade and clinical management was analyzed using Fisher’s exact and Cramer’s V tests.

RESULTS: The systematic reviews found 70 different grading scales with heterogeneous reliability (kappa values from 0.12 to 1.00). The 60-patient portfolio was independently evaluated by 19 raters of diverse backgrounds (neurosurgery, radiology, and neurology) and experience. There was substantial agreement (α_K=0.76, 95%CI, 0.67-0.83) between raters, regardless of background, experience, or treatment used. Intra-rater agreement ranged from moderate to almost perfect. A strong relationship was found between angiographic grades and management decisions (Cramer’s V: 0.80±0.12).

CONCLUSION: A simple 3-point scale demonstrated sufficient reliability to be used in reporting aneurysm treatments or in evaluating treatment results in comparative randomized trials.

PMID:33625550 | DOI:10.1007/s00234-021-02676-0

JAMA Netw Open. 2021 Feb 1;4(2):e210061. doi: 10.1001/jamanetworkopen.2021.0061.

ABSTRACT

IMPORTANCE: Persons with opioid use disorder (OUD) and co-occurring alcohol use disorder (AUD) are understudied and undertreated. It is unknown whether the use of medications to treat OUD is associated with reduced risk of alcohol-related morbidity.

OBJECTIVE: To determine whether the use of OUD medications is associated with decreased risk for alcohol-related falls, injuries, and poisonings in persons with OUD with and without co-occurring AUD.

DESIGN, SETTING, AND PARTICIPANTS: This recurrent-event, case-control, cohort study used prescription claims from IBM MarketScan insurance databases from January 1, 2006, to December 31, 2016. The sample included persons aged 12 to 64 years in the US with an OUD diagnosis and taking OUD medication who had at least 1 alcohol-related admission. The unit of observation was person-day. Data analysis was performed from June 26 through September 28, 2020.

EXPOSURES: Days of active OUD medication prescriptions, with either agonist (ie, buprenorphine or methadone) or antagonist (ie, oral or extended-release naltrexone) treatments compared with days without OUD prescriptions.

MAIN OUTCOMES AND MEASURES: The primary outcome was admission for any acute alcohol-related event defined by International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. Conditional logistic regression was used to compare OUD medication use between days with and without an alcohol-related event. Stratified analyses were conducted between patients with OUD with and without a recent AUD diagnostic code.

RESULTS: There were 8 424 214 person-days of observation time among 13 335 participants who received OUD medications and experienced an alcohol-related admission (mean [SD] age, 33.1 [13.1] years; 5884 female participants [44.1%]). Agonist treatments (buprenorphine and methadone) were associated with reductions in the odds of any alcohol-related acute event compared with nontreatment days, with a 43% reduction for buprenorphine (odds ratio [OR], 0.57; 95% CI, 0.52-0.61) and a 66% reduction for methadone (OR, 0.34; 95% CI, 0.26-0.45). The antagonist treatment naltrexone was associated with reductions in alcohol-related acute events compared with nonmedication days, with a 37% reduction for extended-release naltrexone (OR, 0.63; 95% CI, 0.52-0.76) and a 16% reduction for oral naltrexone (OR, 0.84; 95% CI, 0.76-0.93). Naltrexone use was more prevalent among patients with OUD with recent AUD claims than their peers without AUD claims.

CONCLUSIONS AND RELEVANCE: These findings suggest that OUD medication is associated with fewer admissions for alcohol-related acute events in patients with OUD with co-occurring AUD.

PMID:33625511 | DOI:10.1001/jamanetworkopen.2021.0061

Obesity (Silver Spring). 2021 Mar;29(3):500-511. doi: 10.1002/oby.23090.

ABSTRACT

The basis of heat generated by the human body has been a source of speculation and research for more than 2,000 years. Basal heat production, now usually referred to as resting energy expenditure (REE), is currently recognized as deriving from biochemical reactions at subcellular and cellular levels that are expressed in the energy expended by the body’s 78 organs and tissues. These organs and tissues, and the 11 systems to which they belong, influence body size and shape. Connecting these subcellular-/cellular-level reactions to organs and tissues, and then on to body size and shape, provides a comprehensive understanding of individual differences in REE, a contemporary topic of interest in obesity research and clinical practice. This review critically examines these linkages, their association with widely used statistical and physiological REE prediction formulas, and often-unappreciated aspects of measuring basal heat production in humans.

PMID:33624441 | DOI:10.1002/oby.23090