Category: Statistics

Methods Mol Biol. 2024;2825:309-331. doi: 10.1007/978-1-0716-3946-7_18.

ABSTRACT

Across eukaryotes, genome stability is essential for normal cell function, physiology, and species survival. Aberrant expression of key genes or exposure to genotoxic agents can have detrimental effects on genome stability and contribute to the development of various diseases, including cancer. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a frequent form of genome instability observed in cancer and is a driver of genetic and cell-to-cell heterogeneity that can be rapidly detected and quantitatively assessed using surrogate markers of CIN. For example, single cell quantitative imaging microscopy (QuantIM) can be used to simultaneously identify changes in nuclear areas and micronucleus formation. While changes in nuclear areas are often associated with large-scale changes in chromosome complements (i.e., ploidy), micronuclei are small extra-nuclear bodies found outside the primary nucleus that have previously been employed as a measure of genotoxicity of test compounds. Here, we present a facile QuantIM approach that allows for the rapid assessment and quantification of CIN associated phenotypes and genotoxicity. First, we provide protocols to optimize and execute CIN and genotoxicity assays. Secondly, we present the critical imaging settings, optimization steps, downstream statistical analyses, and data visualization strategies employed to obtain high quality and robust data. These approaches can be easily applied to assess the prevalence of CIN associated phenotypes and genotoxic stress for a myriad of experimental and clinical contexts ranging from direct tests to large-scale screens of various genetic contexts (i.e., aberrant gene expression) or chemical compounds. In summary, this QuantIM approach facilitates the identification of novel CIN genes and/or genotoxic agents that will provide greater insight into the aberrant genes and pathways underlying CIN and genotoxicity.

PMID:38913318 | DOI:10.1007/978-1-0716-3946-7_18

Updates Surg. 2024 Jun 24. doi: 10.1007/s13304-024-01923-2. Online ahead of print.

ABSTRACT

This study aims to explore the safety and efficacy of 3D laparoscopy in elderly patients undergoing transabdominal preperitoneal (TAPP) surgery for inguinal hernia. Patients were divided into two groups based on the laparoscopic equipment used during surgery. Clinical data preoperatively, intraoperatively, and postoperatively were collected and subjected to statistical analysis. From January 2020 to August 2023, a total of 127 patients with primary unilateral inguinal hernia were evaluated in this study, 61 in the 3D TAPP group and 66 in the 2D TAPP group. There were no statistically significant differences in baseline data, including average age, gender distribution, BMI index, hernia type, hernia defect size and location, comorbidities, and usage of anticoagulant drugs between the two groups (P > 0.05). In terms of operative indicators, the 3D group showed shorter mean operation time (51.61 ± 7.16 min vs. 78.59 ± 13.51 min, P < 0.001), mean mesh placement time (6.07 ± 1.40 min vs. 9.77 ± 1.21 min, P < 0.001), and mean peritoneal suture time (7.34 ± 1.85 min vs. 9.73 ± 1.32 min, P < 0.001) compared to the 2D group. However, there were no statistically significant differences in mean blood loss, postoperative pain scores, postoperative hospital stay, and total hospital costs between the two groups (P > 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P > 0.05). No adverse reactions such as dizziness or nausea were reported by surgeons during the procedures in either group. Three-dimensional laparoscopy in TAPP surgery provides high-definition, three-dimensional surgical images, reducing the difficulty of operations and effectively shortening the operation time.

PMID:38913298 | DOI:10.1007/s13304-024-01923-2

Updates Surg. 2024 Jun 24. doi: 10.1007/s13304-024-01918-z. Online ahead of print.

ABSTRACT

The recommended treatment for early stage thymoma without myasthenia gravis is complete thymectomy (CT). Limited thymectomy (LT) (simply resecting the thymoma with safe surgical margins) is gaining popularity. In this study, we compared the surgical and oncological results of complete and limited thymectomy in non-myasthenic patients with early stage thymoma. Non-myasthenic, Masaoka stage I-II, 86 patients who underwent surgical resection for thymoma were included in the study. Complete thymectomy (n:44) included patients who had resection of the thymoma together with the entire thymus and limited thymectomy (n:42) included patients who had resection of the thymoma without remaining thymus. The surgical approach, tumor size, histological type, pathological stage, adjuvant therapy, complications, postop myasthenia gravis, recurrence and death were recorded and compared between groups. Complete thymectomy group had more WHO type B1-3 tumors, more complications and more deaths than patients in the limited thymectomy group (p = 0.03, 0.018 and 0.023 respectively). Although statistically not significant CT group had more recurrences than LT group (11.4%/4.8%, p = 0.43). The 10-year freedom from recurrence (FFR) rate in the CT group was 84.8% and in the LT group ıt was 97.6%, the difference was not statistically significant (p = 0.15). None of the factors including surgical extent analysed with univariate and multivariate analysis had a significant effect on FFR. Limited thymectomy may be a good treatment option for non-myasthenic early stage thymoma patients but randomized controlled trials with long follow-up periods, ideally comparing patients operated with minimally invasive surgery are necessary.

PMID:38913297 | DOI:10.1007/s13304-024-01918-z

Am J Cardiovasc Drugs. 2024 Jun 24. doi: 10.1007/s40256-024-00654-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels.

METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I² index. The risk of bias was assessed using Cochrane’s RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020).

RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = – 63.78, 95% CI – 65.88 to – 61.68, p value < 0.00001, I² = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I² = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I² = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool.

CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations.

REGISTRATION: PROSPERO identifier number CRD42023471020.

PMID:38913274 | DOI:10.1007/s40256-024-00654-4

J Nephrol. 2024 Jun 24. doi: 10.1007/s40620-024-01983-y. Online ahead of print.

ABSTRACT

BACKGROUND: Itching is an annoying symptom which afflicts patients with chronic renal failure. We aimed to assess the impact and patient’s perception and experience of itching in the dialysis population in Italy.

METHODS: A questionnaire was developed by the National Hemodialysis and Dialysis Association of Italy (ANED) and administered to 996 hemodialysis recipients across 153 Italian dialysis centers. The main outcomes investigated by the questionnaire were patients’ satisfaction on answers regarding the nature of itching; continuing to talk about itching with the nephrologist; beliefs about resolution of itching.

RESULTS: A total of 1903 patients from 153 centers responded to the questionnaire. Patients who responded had a mean age of 67.9 ± 13.8 years (63.9% male) and were stratified by itch discomfort graded as mild (35.9%), moderate (29.6%), and severe (34.4%). Severe itching disrupted patients’ daily lives, strained their relationships, caused anxiety, and diminished their quality of life. Patients with severe itch were more likely to talk about it with dialysis staff and to undertake dermatological visits. However, only 18.0% of patients reporting severe itching found the clinicians’ responses satisfactory, compared to 49.1% of mild itch patients. Those who continued talking to nephrologists about itching received more satisfactory response. However, 40.8% believed itching could not be alleviated and were less likely to discuss it with nephrologists.

CONCLUSIONS: There is an intricate relationship between the severity of itching, patient perceptions, and healthcare communication among hemodialysis patients. A substantial proportion of patients experiencing severe itching expressed feelings of resignation, highlighting the pressing need for enhanced clinician-patient communication.

PMID:38913267 | DOI:10.1007/s40620-024-01983-y

J Nephrol. 2024 Jun 24. doi: 10.1007/s40620-024-01984-x. Online ahead of print.

ABSTRACT

BACKGROUND: Although several risk factors of kidney cancer have already been well-addressed, many remain underappreciated, such as chronic exposure to air pollution. This systematic review and meta-analysis aims to assess the association between air pollutant exposure and the risk of kidney cancer.

METHODS: With an exhaustive search equation including keywords related to air pollution and kidney cancer on EMBASE, PubMed, Web of science, Cochrane Library and CINAHL database, we identified all relevant articles published before March 23rd, 2023 (Prospero registration number: CRD42020187956). Using random-effects meta-analysis, we present pooled hazard ratios (with their respective 95% confidence interval) associated with a 10 µg/m³ increase in each pollutant level. Heterogeneity was quantified by the I₂ statistic. Risks of methodological and publication bias were also both assessed using appropriate tools.

RESULTS: Of the 1919 records identified, our review included 19 articles (13 cohort, 5 registry-based and 1 case-control studies), of which 9 were suitable for the meta-analysis. We found a significantly increased risk of kidney cancer incidence for a 10 μg/m³ elevation of both particulate matter of less than 10 µm (PM₁₀) (HR = 1.29 [1.10; 1.51], I² = 0%, p = 0.002) and nitrogen dioxide (NO₂) (HR = 1.10 [1.03; 1.18], I² = 20%, p = 0.004). Secondary analyses also suggest an increased risk of kidney cancer-related morbidity-mortality associated with PM₁₀ exposure.

CONCLUSIONS: Overall, our findings suggest a potential association between exposure to increased levels of PM₁₀ and NO₂ and the risk of kidney cancer. These results should nonetheless be interpreted with caution due to the limited number of included studies and their significant risk of methodological bias.

PMID:38913266 | DOI:10.1007/s40620-024-01984-x

Environ Sci Pollut Res Int. 2024 Jun 24. doi: 10.1007/s11356-024-34060-9. Online ahead of print.

ABSTRACT

The health of humans, animals and the environment is interconnected. Adopting a One Health approach means intervening promptly to prevent the main diseases that affect animal health to guarantee the safety of livestock production. Exposure to toxic trace elements in sheep can lead to increased accumulation in different biological substrate, developing both acute and chronic diseases in humans and livestock. The aim of this study was to evaluate the bioaccumulation of arsenic (As), cadmium (Cd), lead (Pb) and mercury (Hg) in Sicilian Barbaresca sheep using the following biological substrates: milk, blood and fleece. An inductively coupled plasma mass spectrometer (ICP-MS) was used for As, Cd and Pb, and a direct mercury analyser (DMA-80) was used for Hg determination. In addition, the role of the haematological parameters as possible indicators of different biodistribution was evaluated. A statistically significant value was observed from our analysed metals in the substrates: arsenic (p < 0.001), cadmium (p < 0.01), lead (p < 0.001) and mercury (p < 0.0001). The correlation analysis showed a relationship between milk and blood for arsenic (p < 0.0001) and lead (p < 0.0001), and no correlation for the metals was observed between milk/blood and the haematological parameters analysed for the low concentration observed in the present study comforting the final consumer.

PMID:38913265 | DOI:10.1007/s11356-024-34060-9

J Epidemiol Glob Health. 2024 Jun 24. doi: 10.1007/s44197-024-00268-8. Online ahead of print.

NO ABSTRACT

PMID:38913257 | DOI:10.1007/s44197-024-00268-8

Braz J Microbiol. 2024 Jun 24. doi: 10.1007/s42770-024-01413-y. Online ahead of print.

ABSTRACT

The Yanomami are one of the oldest indigenous tribes in the Amazon and are direct descendants of the first people to colonize South America 12,000 years ago. They are located on the border between Venezuela and Brazil, with the Venezuelan side remaining uncontacted. While they maintain a hunter-gatherer society, they are currently experiencing contact with urbanized populations in Brazil. The human gut microbiota of traditional communities has become the subject of recent studies due to the Westernization of their diet and the introduction of antibiotics and other chemicals, which have affected microbial diversity in indigenous populations, thereby threatening their existence. In this study, we preliminarily characterized the diversity of the gut microbiota of the Yanomami, a hunter-gatherer society from the Amazon, experiencing contact with urbanized populations. Similarly, we compared their diversity with the population in Manaus, Amazonas. A metabarcoding approach of the 16 S rRNA gene was carried out on fecal samples. Differences were found between the two populations, particularly regarding the abundance of genera (e.g., Prevotella and Bacteroides) and the higher values of the phyla Bacteroidetes over Firmicutes, which were significant only in the Yanomami. Some bacteria were found exclusively in the Yanomami (Treponema and Succinivibrio). However, diversity was statistically equal between them. In conclusion, the composition of the Yanomami gut microbiota still maintains the profile characteristic of a community with a traditional lifestyle. However, our results suggest an underlying Westernization process of the Yanomami microbiota when compared with that of Manaus, which must be carefully monitored by authorities, as the loss of diversity can be a sign of growing danger to the health of the Yanomami.

PMID:38913252 | DOI:10.1007/s42770-024-01413-y

Eur Radiol. 2024 Jun 24. doi: 10.1007/s00330-024-10850-0. Online ahead of print.

ABSTRACT

OBJECTIVES: To establish normative values and identify potential factors influencing pancreatic iodine uptake using dual-energy CT (DECT).

MATERIALS AND METHODS: This retrospective study included participants without pancreatic diseases undergoing DECT at two institutions with different platforms. Their protocols both included arterial phase (AP), portal venous phase (PP), and equilibrium phase (EP), defined as 35 s-40 s, 60 s-70 s, and 150 s-180 s after injection of contrast agent, respectively. Both iodine concentration (IC) and normalised IC (NIC) were measured. Demographic features, local measurements of the pancreas and visceral fat area (VFA) were considered as potential factors influencing iodine uptake using multivariate linear regression analyses.

RESULTS: A total of 562 participants (median age 58 years [interquartile range: 47-67], with 282 men) were evaluated. The mean IC differed significantly between two institutions (all p < 0.001) across three contrast-enhanced phases, while the mean NIC showed no significant differences (all p > 0.05). The mean values of NIC were 0.22 at AP, 0.43 at PP and 0.45 at EP. NIC_AP was independently affected by VFA (β = 0.362, p < 0.001), smoking (β = -0.240, p = 0.001), and type-II diabetes (β = -0.449, p < 0.001); NIC_PP by VFA (β = -0.301, p = 0.017) and smoking (β = -0.291, p < 0.001); and NIC_EP by smoking (β = -0.154, p = 0.10) and alcohol consumption (β = -0.350, p < 0.001) with statistical power values over 0.81.

CONCLUSION: NIC values were consistent across institutions. Abdominal obesity, smoking, alcohol consumption, and diabetes are independent factors influencing pancreatic iodine uptake.

CLINICAL RELEVANCE STATEMENT: This study has provided reference normative values, influential factors and effective normalisation methods of pancreatic iodine uptake in multiphase dual-energy CT for future studies in this area as a new biological marker.

KEY POINTS: Evaluation of pancreatic iodine uptake measured by dual-energy CT is a promising method for future studies. Abdominal obesity, smoking, alcohol consumption, diabetes, and sex are independent factors influencing pancreatic iodine uptake. Utility of normalised iodine concentration is necessary to ensure the consistency across different institutions.

PMID:38913243 | DOI:10.1007/s00330-024-10850-0