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Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19

JAMA Intern Med. 2022 Aug 18. doi: 10.1001/jamainternmed.2022.3858. Online ahead of print.

ABSTRACT

IMPORTANCE: The risk of venous thromboembolism (VTE) in ambulatory COVID-19 is controversial. In addition, the association of vaccination with COVID-19-related VTE and relevant clinical and genetic risk factors remain to be elucidated.

OBJECTIVE: To quantify the association between ambulatory COVID-19 and short-term risk of VTE, study the potential protective role of vaccination, and investigate clinical and genetic risk factors for post-COVID-19 VTE.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study of patients with COVID-19 from UK Biobank included participants with SARS-CoV-2 infection that was confirmed by a positive polymerase chain test reaction result between March 1, 2020, and September 3, 2021, who were then propensity score matched to COVID-19-naive people during the same period. Participants with a history of VTE who used antithrombotic drugs (1 year before index dates) or tested positive in hospital were excluded.

EXPOSURES: First infection with SARS-CoV-2, age, sex, ethnicity, socioeconomic status, obesity, vaccination status, and inherited thrombophilia.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite VTE, including deep vein thrombosis or pulmonary embolism, which occurred 30 days after the infection. Hazard ratios (HRs) with 95% CIs were calculated using cause-specific Cox models.

RESULTS: In 18 818 outpatients with COVID-19 (10 580 women [56.2%]; mean [SD] age, 64.3 [8.0] years) and 93 179 matched uninfected participants (52 177 women [56.0%]; mean [SD] age, 64.3 [7.9] years), the infection was associated with an increased risk of VTE in 30 days (incidence rate of 50.99 and 2.37 per 1000 person-years for infected and uninfected people, respectively; HR, 21.42; 95% CI, 12.63-36.31). However, risk was substantially attenuated among the fully vaccinated (HR, 5.95; 95% CI, 1.82-19.5; interaction P = .02). In patients with COVID-19, older age, male sex, and obesity were independently associated with higher risk, with adjusted HRs of 1.87 (95% CI, 1.50-2.33) per 10 years, 1.69 (95% CI, 1.30-2.19), and 1.83 (95% CI, 1.28-2.61), respectively. Further, inherited thrombophilia was associated with an HR of 2.05 (95% CI, 1.15-3.66) for post-COVID-19 VTE.

CONCLUSIONS AND RELEVANCE: In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.

PMID:35980616 | DOI:10.1001/jamainternmed.2022.3858

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The effect of medical ozone therapy in addition to ovarian detorsion in ischemia reperfusion model

J Obstet Gynaecol. 2022 Aug 18:1-8. doi: 10.1080/01443615.2022.2109130. Online ahead of print.

ABSTRACT

This study aimed to investigate the protective effect of ozone therapy on ovarian reserve, number of ovarian follicles, ovarian morphology in a rat ischaemia reperfusion (IR) injury model. Twenty-four, Wistar Hannover rats were included. The rats were divided into three groups as control, detorsion-only, and ozone therapy + detorsion groups. There was a statistically significant difference in the follicular damage and inflammation scores between the study groups (p = .019, p = .002, respectively). The highest AMH decrease was observed in the detorsion-only group (p = .012). The total damage score was higher in the detorsion-only group than the ozone therapy + detorsion group. Preantral, small and large antral follicle numbers were less in the detorsion-only group than the ozone therapy + detorsion group. The highest postoperative day 7 TAS level was in the ozone therapy + detorsion group. TOS levels did not differ significantly between the study groups. The combination of the ozone therapy with ovarian detorsion is more effective in protecting the ovarian reserve than ovarian detorsion-only.Impact StatementWhat is already known on this subject? Adnexal torsion is a common gynecological emergency in reproductive-age women. The recommended management is the detorsion of the adnexal pedicle in patients with fertility desire.What do the results of this study add? The combination of the medical ozone therapy with conventional surgical ovarian detorsion is more effective in the protection of the ovarian reserve compared to surgical ovarian detorsion.What are the implications of these findings for clinical practice and/or further research? This study speculates that medical ozone therapy in addition to conventional surgical ovarian detorsion could preserve ovarian reserve and function if confirmed in further clinical studies.

PMID:35980609 | DOI:10.1080/01443615.2022.2109130

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Ultrasound and FibroScan® Controlled Attenuation Parameter in patients with MAFLD: head to head comparison in assessing liver steatosis

Endocrine. 2022 Aug 18. doi: 10.1007/s12020-022-03157-x. Online ahead of print.

ABSTRACT

BACKGROUND: Controlled attenuation parameter (CAP) has been suggested as a new non-invasive measurement performed during transient elastography (TE) to assess liver steatosis. The aim of this study was to evaluate CAP values head to head with ultrasound (US) as reference standard.

METHODS: A consecutive cohort of patients attending abdominal US in an outpatient liver unit was included in this study with simultaneous CAP determination using the FibroScan® M probe and fibrosis scored by TE. Patients were subdivided in four groups on the basis of risk factors for Metabolically Associated Fatty Liver Disease (MAFLD).

RESULTS: Four hundred thirty-five patients were included in the analysis: 221 (51%) were male; 117 (26.9%) were in control group, 144 (33.1%) in group 2 with inactive HCV or HBV infection and at low-risk for MAFLD, 134 (30.8%) in group 3 at high-risk of MAFLD, 40 (9.2%) in group 4 at high-risk of MAFLD and concomitant inactive HCV or HBV infection. Liver steatosis detected with US evaluation was observed in the 41% of the entire cohort; in particular in the 3.4%, 20.1%, 83.6% and 87.4% of the group 1, 2, 3 and 4, respectively (p < 0.001). In patients at high-risk factor for MAFLD (group 3 and 4), CAP median levels were found statistically different among the severity-grading groups for US steatosis (S0 [n.27], ≥S1 [n.59], ≥S2 + S3 [n.89]), observing higher CAP levels in patients with a higher steatosis grade (≥S2 + S3 327.5 [±40.6] vs ≥S1 277.7 [±45.6] vs S0 245.1 [±47.4]; p < 0.001 for the whole cohort analysis) (p < 0.001 between ≥S2 + S3 and ≥S1) (p < 0.001 between ≥S2 + S3 and S0) (p = 0.004 between ≥S1 and S0). ROC analysis showed that the global performance of the CAP median level ≥ 258 to predict liver steatosis (S0 vs S1-3), was excellent with an Area Under the Curve (AUC) value of 0.87 [CI 95% 0. 835-0.904] with an 84% of sensitivity and a 78% of specificity, and a positive predictive value (PPV) of 73% and negative predictive value (NPV) of 88%. A TE-kPa median value <8.0 was detected in the 100%, 84%, 83.6% and 60% of patients in group 1, 2, 3 and 4, respectively. A TE-kPa median value >13.0 was detected in the 0%, 4.2%, 5.2% and 17.5% of patients in group 1, 2, 3 and 4, respectively.

CONCLUSIONS: CAP values are strongly associated with the standard US criteria for different degree of steatosis. Integrating TE up to 5% of patients may be identified at risk for advanced fibrosis.

PMID:35980569 | DOI:10.1007/s12020-022-03157-x

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Expression and Prognostic Significance of Stem Cell Marker CD133 in Survival Rate of Patients with Colon Cancer

Oncol Ther. 2022 Aug 18. doi: 10.1007/s40487-022-00205-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Today, colon cancer is one of the most common types of gastrointestinal cancer worldwide. CD133 as a known cancer stem cell marker has been found effective in cell proliferation and differentiation in various cancers, including colon cancer. We aimed to investigate the relationship between CD133 expression in colon cancer with prognostic factors and survival rate of patients with colon cancer by immunohistochemistry.

METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue was taken from patients with colon cancer. Histopathology examination was done using hematoxylin and eosin staining. Immunohistochemistry was performed to determine CD133 expression. Association between CD133 expression and clinicopathological profile was then assessed.

RESULTS: There was a statistically significant association between CD133 protein expression and sex , cancer stage, and lymphatic invasion (p = 0.044, p = 0.131, and p = 0.002, respectively). However, no significant correlation was identified between CD133 expression and other factors, including age of patients with colorectal cancer (CRC) (p = 0.267), tumor location (p = 0.494), tumor differentiation grade (p = 0.263), neural tissue invasion, and 5-year survival (p = 0.054).

CONCLUSION: CD133 is a useful predictive or prognostic biomarker for CRC in clinical assessment and may serve as a potential therapeutic target for CRC.

PMID:35980560 | DOI:10.1007/s40487-022-00205-4

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Tumor Growth Rate as a Predictive Marker for Recurrence and Survival After Liver Resection in Patients with Liver Metastases of Uveal Melanoma

Ann Surg Oncol. 2022 Aug 18. doi: 10.1245/s10434-022-12368-5. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical management of liver metastases of uveal melanoma (LMUM) is associated with the best survival rates, especially for patients with a low tumor burden in the liver. The aim was to determine whether the tumor growth rate (TGR0) before liver resection helps predict survival in patients with resectable LMUM.

METHODS: This retrospective study included 99 patients with LMUM treated with liver resection between November 2007 and November 2020. TGR0 was expressed as the percentage change in tumor volume over 1 month according to two pretreatment imaging scans. Multivariate Cox analyses identified independent predictors of disease-free survival (DFS) and overall survival (OS).

RESULTS: DFS and OS had a statistically significant positive linear relationship (Spearman correlation r = 0.68, p < 0.001). A disease-free interval (DFI) > 24 months and a TGR0 ≤ 50%/month were independent factors associated with better DFS and OS. The 2-component model including TGR0 and DFI had a mean time-dependent area under the curve (AUC) of 0.81 (95% CI, 0.75-0.86) and 0.77 (95% CI, 0.67-0.87), respectively, for predicting DFS and OS. DFI with TGR0 defined three kinetic risk groups that had distinct DFS and OS outcomes (p < 0.001). Cytogenetic alterations at baseline were partially predictive factors of the kinetic risk score based on TGR0 and DFI.

DISCUSSION: The assessment of TGR0 improves prognostic stratification by identifying patients at high risk of recurrence and poor survival after liver resection. TGR0 and DFI, reflecting tumor aggressivity, have the potential to be important markers for systemic adjuvant decisions.

PMID:35980554 | DOI:10.1245/s10434-022-12368-5

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A Comprehensive Comparison of Different Nodal Subclassification Methods in Surgically Resected Non-Small-Cell Lung Cancer Patients

Ann Surg Oncol. 2022 Aug 18. doi: 10.1245/s10434-022-12363-w. Online ahead of print.

ABSTRACT

INTRODUCTION: The revision of the N descriptor in non-small-cell lung cancer has been widely discussed in the past few years. Many different subclassification methods based on number or location of lymph nodes have been proposed for better distinguishing different N patients. This study aimed to systematically collect them and provide a comprehensive comparison among different subclassification methods in a large cohort.

METHOD: Pathological N1 or N2 non-small-cell lung cancer patients undergoing surgical resection between 2005 and 2016 in the Western China Lung Cancer Database were retrospectively reviewed. A literature review was conducted to collect previous subclassification methods. Kaplan-Meier and multivariable Cox analyses were used to examine the prognostic performance of subclassification methods. Decision curve analysis, Akaike’s information criterion, and area under the receiver operating curve concordance were also performed to evaluate the standardized net benefit of the subclassification methods.

RESULTS: A total of 1625 patients were identified in our cohort. Eight subclassification methods were collected from previous articles and further grouped into subclassification based on number categories (node number or station number), location categories (lymph node zone or chain) or combination of number and location categories. Subclassification based on combination of lymph node location and number tended to have better discrimination ability in multivariable Cox analysis. No significant superiority among the different subclassification methods was observed in the three statistical models.

CONCLUSION: Subclassification based on the combination of location and number could be used to provide a more accurate prognostic stratification in surgically resected NSCLC and is worth further validation.

PMID:35980551 | DOI:10.1245/s10434-022-12363-w

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Microaerobic conditions enhance laccase production from Rheinheimera sp. in an economical medium

Arch Microbiol. 2022 Aug 18;204(9):562. doi: 10.1007/s00203-022-03170-8.

ABSTRACT

Statistical optimization of aeration conditions viz. aerobic, microaerobic and anaerobic, was performed using response surface methodology (RSM) utilizing soybean meal as medium to enhance the production of laccase from Rheinheimera sp. Maximum laccase yield (18.48 × 105 U/L) was obtained under microaerobic (static) conditions sustained for 12 h in tandem with 26 h aerobically (150 rpm) grown culture, which was 17.03-fold higher than laccase production in the starting M162 medium under aerobic conditions (150 rpm). The reduction in incubation time from 72 to 38 h and utilization of cost-effective soybean meal as medium, which is easily available from local market, have provided a promising, eco-friendly method of laccase enzyme production. Enhanced expression of laccase gene under microaerobic conditions corresponded to the increased expression of fnr (fumarate nitrate reductase) gene, the oxygen sensing global regulator. The putative FNR-binding site upstream of laccase transcription initiation site was predicted to play an imperative role in Rheinheimera sp. adaptation from aerobic to microaerobic conditions and for enhanced laccase production.

PMID:35980477 | DOI:10.1007/s00203-022-03170-8

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Biaxial flexure strength and physicochemical characterization of a CAD/CAM lithium disilicate ceramic: effect of etching time, silane, and adhesive applications

Clin Oral Investig. 2022 Aug 18. doi: 10.1007/s00784-022-04635-2. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effect of different acid etching time and bonding agent (silane and/or adhesive system) on biaxial flexural strength and physico-chemical properties of a lithium disilicate ceramic.

MATERIAL AND METHODS: One hundred twenty ceramic discs were made and divided into 8 groups (n = 15) according to factors “etching time” (20 and 120 s) with hydrofluoric acid (HF) and “bonding agent” (C, no bonding agent; S, silane, A, adhesive; and SA, silane + adhesive). After surface treatment, a resin cement layer was applied to the surface and all specimens were subjected to biaxial flexural strength (BFS) test with treated surfaces loaded in tension (1 mm/min). The Weibull analyses and complementary analyses were also performed. Statistical analysis was done with 2-way ANOVA and the Tukey test (α = 0.05).

RESULTS: ANOVA revealed that the factors “etching time” (p = 0.0003) and “bonding agent” (p = 0.007) were statistically significant. In the overall analysis, the HF120S group (272.02 ± 35.30A MPa) presented significantly higher BFS than that of HF120C (218.45 ± 17.15CD MPa) and HF20S (228.40 ± 37.83BCDMPa). On the other hand, the HF20A group (208.92 ± 31.16D MPa) had significantly lower BFS than HF120S (272.02 ± 35.30A), HF120A (254.42 ± 26.87ABC) and HF120SA (259.30 ± 36.55AB) groups (Tukey). The Weibull modulus (m) of all groups was significantly different from each other (p = 0.000).

CONCLUSIONS: Regardless of etching time, the application of silane alone is sufficient to increase the flexural strength of glass ceramic, eliminating the need for the application of adhesive systems. Moreover, if only silane or adhesive is applied, 120-s HF application should increase the flexural resistance of the lithium disilicate ceramic.

CLINICAL SIGNIFICANCE: Applications of adhesive systems after silanization can be suppressed from the surface treatment protocol of glass ceramics, since it does not improve their mechanical strength.

PMID:35980474 | DOI:10.1007/s00784-022-04635-2

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Grade group 1 prostate cancer on biopsy: are we still missing aggressive disease in the era of image-directed therapy?

World J Urol. 2022 Aug 18. doi: 10.1007/s00345-022-04130-z. Online ahead of print.

ABSTRACT

PURPOSE: Recently, Eggener et al. reignited a debate consisting to redefine Gleason Grade Group (GGG) 1 prostate cancer (PCa) as a precancerous lesion to reduce overdiagnosis and overtreatment. However, historical cohorts showed that some GGG1-labeled disease at biopsy may be underestimated by the standard PCa diagnostic workup. The aim was to assess whether the risk of adverse features at radical prostatectomy (RP) in selected GGG1 patients still exists in the era of pre-biopsy mpMRI and image-guided biopsies.

METHODS: We retrospectively reviewed our data from a European RP dataset to assess in contemporary patients with GGG1 at mpMRI-targeted biopsy the rate of adverse features at final pathology, defined as ≥ pT3a and/or pN+ and/or GGG ≥ 3.

RESULTS: A total of 419 patients with cT1-T2 cN0 GGG1-PCa were included. At final pathology, 143 (34.1%) patients had adverse features. In multivariate analysis, only unfavorable intermediate-risk/high-risk disease (defined on PSA or stage) was predictive of adverse features (OR 2.45, 95% CI 1.11-5.39, p = 0.02). A significant difference was observed in the 3-year biochemical recurrence-free survival between patients with and without adverse features (93.4 vs 87.8%, p = 0.026). In sensitivity analysis restricted low- and favorable intermediate-risk PCa, 122/383 patients (31.8%) had adverse features and no preoperative factors were statistically associated with this risk.

CONCLUSION: In this European study, we showed that there is still a risk of underestimating GGG1 disease at biopsy despite the routine use of image-guided biopsies. Future studies are warranted to improve the detection of aggressive disease in GGG1-labeled patients by incorporating the latest tools such as genomic testing or radiomics.

PMID:35980449 | DOI:10.1007/s00345-022-04130-z

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Changes in the first anti-seizure medication prescribed for children and adolescents with epilepsy in a tertiary clinical center in Serbia over two decades

Int J Clin Pharmacol Ther. 2022 Aug 18. doi: 10.5414/CP204236. Online ahead of print.

ABSTRACT

OBJECTIVES: We assessed the prevalence of the use of new anti-seizure medications and valproate in the female population over two decades.

MATERIALS AND METHODS: We conducted a retrospective observational cross-sectional study of medical records of children and adolescents (4 – 19 years old) with newly diagnosed epilepsy in a tertiary clinical center in Serbia from 1997 to 1999 and 2017 to 2019.

RESULTS: The statistical analysis revealed significant changes in the treatment of generalized and focal seizures and all etiologies of epilepsy. Valproate use in the adolescent girl population decreased significantly from 2017 to 2019.

CONCLUSION: The prescription pattern of the initial anti-seizure medication changed significantly over the two decades. The results correspond to current guidelines and recommendations.

PMID:35979899 | DOI:10.5414/CP204236