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Nevin Manimala Statistics

Impact of Anti-EGFR Therapies on HER2-Positive Metastatic Colorectal Cancer: A Systematic Literature Review and Meta-Analysis of Clinical Outcomes

Oncologist. 2023 Jul 18:oyad200. doi: 10.1093/oncolo/oyad200. Online ahead of print.

ABSTRACT

BACKGROUND: HER2 overexpression/amplification in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) may be associated with resistance to standard-of-care anti-EGFR therapies. Given the lack of comprehensive investigations into this association, we assessed the prognostic or predictive effect of HER2 amplification/overexpression on anti-EGFR treatment outcomes.

METHODS: A systematic review of MEDLINE, Embase, and Cochrane Library (2001-2021) identified studies evaluating progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in HER2-positive vs. HER2-negative patients with RAS WT mCRC who received anti-EGFR treatments and whose HER2 status was known. Meta-analyses of proportions (ORR) and hazard ratios (PFS, OS) were performed using random-effect models with pre-specified sensitivity analyses.

RESULTS: Five high-quality retrospective cohort studies were included in the meta-analyses representing 594 patients with mCRC. All patients received anti-EGFR treatment, either as monotherapy or in combination with chemotherapy. Meta-analysis of PFS demonstrated a 2.84-fold higher risk of death or progression (95% CI, 1.44-5.60) in patients with HER2-positive (vs. HER2-negative) RAS WT mCRC treated with anti-EGFR regimens. The odds of response to anti-EGFR treatment were 2-fold higher in HER2-negative vs. HER2-positive (odds ratio, 1.96 [95% CI, 1.10-3.48]). Differences in OS were not statistically significant. Sensitivity analyses confirmed the robustness of the base-case estimates.

CONCLUSIONS: While this study could not account for all confounding factors, in patients with RAS WT mCRC who received anti-EGFR therapy, HER2 overexpression/amplification was associated with worse PFS and ORR and may therefore predict poorer outcomes. HER2 testing is important to inform treatment decisions and could optimize outcomes for patients.

PMID:37463037 | DOI:10.1093/oncolo/oyad200

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Determinants of Inadequate Health Literacy Among Faculty of Medical Technical Sciences Students in Albania: Cross-Sectional Survey

JMIR Form Res. 2023 Jul 18;7:e46476. doi: 10.2196/46476.

ABSTRACT

BACKGROUND: Health literacy (HL) refers to people’s ability to find, understand, and use health information in order to make appropriate health decisions. Health literacy among students is important so that tomorrow’s health professionals can deliver high-quality health care and enhance patient education and communication.

OBJECTIVE: In this context, the aim of this study was to assess the HL level of Faculty of Medical Technical Sciences (FMTS) students in order to shed light on this underresearched topic in Albanian settings.

METHODS: A cross-sectional study involving 193 FMTS students of various study branches (nursing, midwifery, physiotherapy, and laboratory technician) was carried out during June 22-29, 2022, on the premises of the FMTS Faculty in Tirana, Albania. The international European Health Literacy Survey Questionnaire (HLS-EU-Q) standardized questionnaire, validated in Albanian, was used to collect information about FMTS students’ general HL through a face-to-face interview. Basic sociodemographic information was collected as well. Binary logistic regression was used to assess the factors associated with inadequate, problematic, or limited HL.

RESULTS: The mean level of general HL was 37.2 (on a scale from 0 [minimum HL] to 50 [maximal HL]). About one-quarter of FMTS students had inadequate (9/193, 4.7%) or problematic (38/193, 19.7%) HL, 51.3% (99/193) had sufficient HL, and 24.4% (47/193) had excellent HL. The prevalence of limited HL (inadequate and problematic HL) was higher among male than female students (6/12, 50% vs 41/181, 22.6%, respectively) and those with lower social and economic status. Upon adjusting for confounding effects, the only factor significantly increasing the likelihood of limited HL was male gender (odds ratio 8.13, 95% CI 1.68-39.39). Findings suggested that low social and economic status also increased the likelihood of limited HL, but such associations did not reach statistical significance.

CONCLUSIONS: To our knowledge, this is the first study exploring the level of HL and its associated factors among FMTS students in Albania. The prevalence of limited HL was relatively high among FMTS students. There is a need for targeted interventions to increase the HL of nursing and midwifery students, such as the inclusion of HL subjects in the nursing curriculum.

PMID:37463034 | DOI:10.2196/46476

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Vesicourethral Anastomosis in Transvesical Single-Port Robotic Radical Prostatectomy (SP-RARP): A Technical Description and Perioperative Outcomes

J Endourol. 2023 Jul 18. doi: 10.1089/end.2023.0269. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the technical evolution and perioperative outcomes of vesicourethral anastomosis (VUA) in Transvesical (TV) Single-Port Robot-Assisted Radical Prostatectomy (SP-RARP).

METHODS: A retrospective review was performed on 189 patients who underwent TV SP-RARP by a single surgeon using the purpose-built SP robotic platform. VUA was completed from within the bladder using two unidirectional V-loc sutures in a continuous, semicircular fashion with greater emphasis posteriorly. The most recent 20 cases of TV SP-RARP were selected to evaluate the anastomosis technique and to compare the perioperative outcomes with the first 20 cases of TV SP-RARP performed at our institution. Demographic and clinical data were collected from the prospectively maintained database and statistical analysis was performed.

RESULTS: VUA was successfully completed in all cases using the aforementioned technique without any suture breaks, conversion, or evidence of intraoperative complication including urine leak. Marked improvement in the learning curve was observed, resulting in significant reduction in the number of VUA sutures (median: 13 vs. 15, p<0.05) and faster anastomosis time (median: 19.1 vs. 33.5 minutes, p<0.05). The number of anastomotic sutures did not correlate with the prostatectomy specimen weight or volume, especially with both being significantly greater in the latest cases (median weight: 45.1 vs. 37.6 grams, p<0.05; median volume: 40.9 vs. 36.2 mL, p<0.05). Postoperative outcomes were favorable with immediate continence achieved in 51.3% of our total cohort and with no patients demonstrating evidence of bladder neck contracture.

CONCLUSION: We provided a detailed technical description of VUA in TV SP-RARP. The improved maneuverability of the SP robotic platform allowed for unique movements to facilitate suture placements from within the confined space of the bladder. The learning curve of a single surgeon was shown in our study, which resulted in notable reduction in the number of sutures, faster anastomosis time, and improved perioperative outcomes.

PMID:37463019 | DOI:10.1089/end.2023.0269

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KIT/PDGFRA Variant Allele Frequency as Prognostic Factor in Gastrointestinal Stromal Tumors (GISTs): Results From a Multi-Institutional Cohort Study

Oncologist. 2023 Jul 18:oyad206. doi: 10.1093/oncolo/oyad206. Online ahead of print.

ABSTRACT

BACKGROUND: The patient selection for optimal adjuvant therapy in gastrointestinal stromal tumors (GISTs) is provided by nomogram based on tumor size, mitotic index, tumor location, and tumor rupture. Although mutational status is not currently used to risk assessment, tumor genotype showed a prognostic influence on natural history and tumor relapse. Innovative measures, such as KIT/PDGFRA-mutant-specific variant allele frequency (VAF) levels detection from next-generation sequencing (NGS), may act as a surrogate of tumor burden and correlate with prognosis and overall survival of patients with GIST, helping the choice for adjuvant treatment.

PATIENTS AND METHODS: This was a multicenter, hospital-based, retrospective/prospective cohort study to investigate the prognostic role of KIT or PDGFRA-VAF of GIST in patients with radically resected localized disease. In the current manuscript, we present the results from the retrospective phase of the study.

RESULTS: Two-hundred (200) patients with GIST between 2015 and 2022 afferent to 6 Italian Oncologic Centers in the EURACAN Network were included in the study. The receiver operating characteristic (ROC) curves analysis was used to classify “low” vs. “high” VAF values, further normalized on neoplastic cellularity (nVAF). When RFS between the low and high nVAF groups were compared, patients with GIST with KIT/PDGFRA nVAF > 50% showed less favorable RFS than patients in the group of nVAF ≤ 50% (2-year RFS, 72.6% vs. 93%, respectively; P = .003). The multivariable Cox regression model confirmed these results. In the homogeneous sub-population of intermediate-risk, patients with KIT-mutated GIST, the presence of nVAF >50% was statistically associated with higher disease recurrence.

CONCLUSION: In our study, we demonstrated that higher nVAF levels were independent predictors of GIST prognosis and survival in localized GIST patients with tumors harboring KIT or PDGFRA mutations. In the cohort of intermediate-risk patients, nVAF could be helpful to improve prognostication and the use of adjuvant imatinib.

PMID:37463014 | DOI:10.1093/oncolo/oyad206

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Relative Ellipsoid Zone Reflectivity in Macular Telangiectasia Type 2

Invest Ophthalmol Vis Sci. 2023 Jul 3;64(10):21. doi: 10.1167/iovs.64.10.21.

ABSTRACT

PURPOSE: The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages.

METHODS: The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls. MacTel disease severity was classified according to Gass and Blodi.

RESULTS: Linear mixed-model analysis of 145 eyes of 74 patients and 50 eyes of 25 controls revealed globally lower, yet not statistically significant, rEZR values in MacTel eyes. Topographically, most pronounced decreases were found in stages 3 and 4/5 for the temporal inner (coefficient estimates [CEs] = -25.4 [-38.2; -12.6] and -34.1 [-48.7; -19.6] AU, both: P < 0.001), the inferior inner (-29.9 [-44.6; -15.6] and -35.3 [-52.1; -18.5] AU, both: P < 0.001), the nasal inner (-21.5 [-35.52; -7.4] and -31.6 [-47.6; -15.6] AU, P = 0,003 and P < 0.001), and in the superior inner subfield of stage 4/5 (-25.0 [-42.0; -7.9] AU, P = 0.004).

CONCLUSIONS: The rEZR showed association with disease severity and the predilection area of MacTel. Given the current understanding of the pathophysiological concept of MacTel, these findings underscore the value of the rEZR as a potential novel biomarker for outer retinal integrity. Longitudinal studies are demanded to better characterize its value as a biomarker for early photoreceptor alterations and disease progression in MacTel.

PMID:37462978 | DOI:10.1167/iovs.64.10.21

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Association of Increasing the Minimum Wage in the US With Experiences of Maternal Stressful Life Events

JAMA Netw Open. 2023 Jul 3;6(7):e2324018. doi: 10.1001/jamanetworkopen.2023.24018.

ABSTRACT

IMPORTANCE: Exposure to stressful life events (SLEs) before and during pregnancy is associated with adverse health for pregnant people and their children. Minimum wage policies have the potential to reduce exposure to SLEs among socioeconomically disadvantaged pregnant people.

OBJECTIVE: To examine the association of increasing the minimum wage with experience of maternal SLEs.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study included 199 308 individuals who gave birth between January 1, 2004, and December 31, 2015, in 39 states that participated in at least 2 years of the Pregnancy Risk Assessment Monitoring Survey between 2004 and 2015. Statistical analysis was performed from September 1, 2022, to January 6, 2023.

EXPOSURE: The mean minimum wage in the 2 years prior to the month and year of delivery in an individual’s state of residence.

MAIN OUTCOMES AND MEASURES: The main outcomes were number of financial, partner-related, traumatic, and total SLEs in the 12 months before delivery. Individual-level covariates included age, race and ethnicity, marital status, parity, educational level, and birth month. State-level covariates included unemployment, gross state product, uninsurance, poverty, state income supports, political affiliation of governor, and Medicaid eligibility levels. A 2-way fixed-effects analysis was conducted, adjusting for individual and state-level covariates and state-specific time trends.

RESULTS: Of the 199 308 women (mean [SD] age at delivery, 25.7 [6.1] years) in the study, 1.4% were American Indian or Alaska Native, 2.5% were Asian or Pacific Islander, 27.2% were Hispanic, 17.6% were non-Hispanic Black, and 48.8% were non-Hispanic White. A $1 increase in the minimum wage was associated with a reduction in total SLEs (-0.060; 95% CI, -0.095 to -0.024), financial SLEs (-0.032; 95% CI, -0.056 to -0.007), and partner-related SLEs (-0.019; 95% CI, -0.036 to -0.003). When stratifying by race and ethnicity, minimum wage increases were associated with larger reductions in total SLEs for Hispanic women (-0.125; 95% CI, -0.242 to -0.009).

CONCLUSIONS AND RELEVANCE: In this repeated cross-sectional study of women with a high school education or less across 39 states, an increase in the state-level minimum wage was associated with reductions in experiences of maternal SLEs. Findings support the potential of increasing the minimum wage as a policy for improving maternal well-being among socioeconomically disadvantaged pregnant people. These findings have relevance for current policy debates regarding the minimum wage as a tool for improving population health.

PMID:37462972 | DOI:10.1001/jamanetworkopen.2023.24018

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Artificial intelligence-based fluorescence method versus traditional flow cytometry in detection of sperm DNA fragmentation index

Zhonghua Nan Ke Xue. 2022 Mar;28(3):227-231.

ABSTRACT

OBJECTIVE: To compare the result of the artificial intelligence (AI) recognition-based fluorescence method and that of traditional flow cytometry in the examination of the sperm DNA fragmentation index (DFI) and assess the reliability of the AI-based fluorescence detection.

METHODS: Using flow cytometry and the AI-based fluorescence method, we examined the sperm DFI in the semen samples collected from 338 outpatients. We analyzed the correlation between the results and compared the positive rates detected by the two methods. We repeated the AI-based fluorescence method twice for each semen sample to observe its technical stability in the detection of sperm DFI.

RESULTS: The result of flow cytometry was well correlated with that of the AI-based fluorescence method in the detection of sperm DFI (R2 = 0.7131), but poorly correlated for low-concentration, sticky semen and some other extreme samples (R2 = 0.2065). No statistically significant difference was found between the two methods in the positive rate of detection. The AI-based fluorescence method exhibited an excellent technical stability (R2 = 0.9671).

CONCLUSION: The AI-based fluorescence method has an excellent technical stability in the detection of sperm DFI and the result is not significantly different from that of traditional flow cytometry.

PMID:37462961

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Correlation of seminal plasma elastase with sperm reactive oxygen species and semen parameters in infertile men

Zhonghua Nan Ke Xue. 2022 Mar;28(3):223-226.

ABSTRACT

OBJECTIVE: To investigate the relationship of seminal plasma elastase (SPE) with sperm reactive oxygen species (ROS) and semen parameters in infertile men.

METHODS: Between July 2021 and December 2021, a total of 145 subjects aged 20-51 years with male infertility were enrolled. SPE, seminal leukocytes, sperm ROS, DNA fragmentation index (DFI) and other semen parameters were detected. We divided patients into an inflammation group (SPE ≥ 290 ng/ml, n = 48) and a non-inflammation group (SPE < 290 ng/ml, n = 97), analyzed the relationship of SPE with seminal leukocytes, sperm ROS, semen volume, sperm concentration, total sperm motility, the percentages of progressively motile sperm (PMS) , morphologically normal sperm (MNS), and DFI.

RESULTS: The concentration of seminal leukocytes, sperm ROS level and DFI were significantly higher in inflammation group than in non-inflammation group (P < 0.05). No statistically significant differences were observed in semen volume, sperm concentration, total sperm motility, PMS, MNS or sperm deformity index (SDI) between two groups of patients (P > 0.05). Spearman correlation analysis showed that the SPE level was correlated positively with the concentration of seminal leukocytes (r = 0.658, P < 0.01), sperm ROS level (r = 0.229, P = 0.006) and DFI (r = 0.192, P = 0.021), but not correlated with semen volume, sperm concentration, total sperm motility, PMS, MNS or SDI (P > 0.05).

CONCLUSION: The level of seminal plasma elastase is related with the concentration of seminal leukocytes, sperm ROS level and DFI, and has some reference value in the diagnosis of male infertility.

PMID:37462960

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Neolamarckia cadamba (cadamba) waste pulp as a natural and techno-economic scavenger for methylene blue from aqueous solutions

Int J Phytoremediation. 2023 Jul 18:1-11. doi: 10.1080/15226514.2023.2232861. Online ahead of print.

ABSTRACT

In this work, Neolamarckia cadamba (cadamba), also known as bur flower tree has been exercised to demonstrate as an excellent methylene blue scavenger from simulated as well as industrial wastewater. The particle morphology and structural insights were gained from FESEM, BET surface area, FTIR, and pHZPC. The adsorption behavior was mapped by different physico-chemical parameters such as contact time, pH, input concentration, and temperature. Experimental data reveal rapid adsorption, and >90% uptake was successful within the first 15 min and reaches equilibrium by 45 min (removal efficiency = 94.15%) at neutral pH. The maximum adsorption capacity was found to be 115.60 mg/g. The uptake process follows pseudo-second-order kinetics (R2 = 0.99), confirming a chemisorption process while the Langmuir model (R2 = 0.99) satisfactorily addresses the adsorption path. Thermodynamic parameters suggest a spontaneous, feasible, and exothermic process with increased entropy. Spent adsorbent could easily be regenerated in up to 74% using 1:1 MeOH/H2O with a potential of three-cycle use. Real-time efficacy has been established with an MB containing industrial effluent and up to 44.70% adsorption, which confirms the material’s practical applicability. Statistical reliability was confirmed by the relative standard deviation. Altogether, the present material offers clean and green removal of methylene blue dye from versatile wastewater.

PMID:37462946 | DOI:10.1080/15226514.2023.2232861

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Persistent Proclivity to a Proinflammatory State in a Human Enteroid Model of Necrotizing Enterocolitis

Surg Infect (Larchmt). 2023 Jul 18. doi: 10.1089/sur.2023.123. Online ahead of print.

ABSTRACT

Background: Necrotizing enterocolitis (NEC) is a devastating disease of premature neonates with substantial morbidity and mortality. Necrotizing enterocolitis is associated with prematurity, a hyperinflammatory response, and dysregulation of intestinal barrier function. We hypothesize that patients with NEC will have an increased hyperinflammatory intestinal response compared with those without NEC. Patients and Methods: Enteroids were generated from intestinal tissue from neonates undergoing resection. They were treated with 100 mcg/mL lipopolysaccharide (LPS), subjected to 24 hours of hypoxia inducing experimental NEC, then compared with untreated controls. Expression of tumor necrosis factor (TNF-α) and interleukin 8 (IL-8) were evaluated via reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) to measure inflammatory response. Analysis of variance (ANOVA) determined statistical significance (p < 0.05). Results: Treated NEC-derived enteroids expressed significantly higher levels of IL-8 (RT-qPCR, p = 0.003; ELISA, p = 0.0002) compared with untreated NEC-derived enteroids with an increase in inflammatory marker concentration in those with a greater degree of prematurity (ELISA, p = 0.0015). A higher level of IL-8 was seen in NEC-derived enteroids compared with control after treatment (RT-qPCR, p = 0.024). Tumor necrosis factor-α levels were elevated in treated NEC-derived enteroids compared with untreated NEC-derived enteroids (RT-qPCR, p = 0.006; ELISA, p = 0.002) and compared with treated non-NEC-derived enteroids (RT-qPCR, p = 0.025; ELISA, p < 0.0001). Conclusions: Enteroids generated from neonates with NEC have an elevated hyperinflammatory response in response to NEC-inducing stimuli compared with controls. Enteroids generated from neonates with NEC with a greater degree of prematurity have a larger increase in inflammatory markers. This tendency toward a hyperinflammatory state may be correlated with an infant’s proclivity to develop NEC and further demonstrates the hyperinflammatory state of prematurity.

PMID:37462922 | DOI:10.1089/sur.2023.123